The use of AI in imaging for Alzheimer’s Disease

Posted on November 15, 2024 by Adriana Gonzalez

The use of AI in imaging for Alzheimer’s Disease

October 2024

The AD landscape is complex but evolving with the recent approval of amyloid-targeting therapies (ATTs), which have enabled an economy built around supporting the new unmet needs created by these therapies

Barriers to address for improving patient outcomes

Diagnosis

PCPs are not set up for success to provide adequate workup
Current cognitive and functional tests have limitations and require repeat testing to detect decline over time
Blood biomarkers (BBMs) can address some of these limitations but are yet to be FDA-approved
The use of AI technology can help accelerate image processing and interpretation, aiding with diagnosis

Integration

AI-powered software that can seamlessly integrate with MRI and PET scan devices could alleviate long waiting time
Hiring and training required personnel needed to carry out all required steps for diagnosis and medication administration (eg, there is a need for more radiologists as current imaging centers have bandwidth issues)
There currently appear to be no major partnerships between companies providing AI-powered software and care systems

On this page, we will provide an overview on the use of AI-powered software for MRI and PET scan imaging interpretation, including the landscape, available tests, and industry trends

EXECUTIVE SUMMARY – THE AI LANDSCAPE SPACE TODAY

AI-powered software tackling some of the main unmet need have already been developed and are currently awaiting FDA 510(k) approval

Current AI-powered software are designed for a broader usein neurology

Current AI-powered software have been developed for not only Alzheimer’s disease but for a larger number of neurodegenerative diseases, such as looking at changes in white and grey matter and volumetric changes
The approval of ATTs has created a new set of needs and challenges that current approved products do not address, like the need for centiloid count on PET scans

Adding functionalities such as ARIA monitoring can help address some of the unmet needs created by ATTs

Software addressing some of the unique unmet needs like detecting and monitoring for ARIA are currently awaiting FDA 510(k) approval and could be granted as early as Q1 2025
Different pricing models, such as subscription-based models or pay-as-you-go models, could help with the adoption of these technologies in large and small healthcare systems

Did you know?

ARIA is one of the side effects of monoclonal antibodies directed to amyloid beta aggregates such as lecanemab and donanemab

EXECUTIVE SUMMARY – THE FUTURE AI IMAGING LANDSCAPE

Ease of integration and additional features that can aid with image interpretation and diagnosis will be key moving forward

Unmet need: Testing for multiple targets yields the most promising outcomes

Future trends: Ability to detect ARIA-E and ARIA-H events and additional features, such as the ability to detect the potential risk of developing ARIA, could help improve the safety of ATT

Unmet need: Most companies currently only offer one payment system, although some have shifted to provide multiple options

Future trends: Having different pricing models for different healthcare systems could help those with large or small volume of patients

Unmet need: The need to integrate with a cloud-based AI could help with faster computation and analysis but have the risk of not being available if there are connectivity issues

Future trends: Products that don’t over-rely on an internet connection for some of their key features could bypass this issue, although computational analysis could be compromised

There is great potential for the use of AI in helping neurologists and radiologists with diagnosis and monitoring for safety, yet FDA approval is critical for their adoption in the real world

Detailed Report

AI imaging could be used alongside BBMs to reduce the need for CSF testing in AD; however, it is unlikely to replace CSF testing as a standalone modality in the near-term

Drivers of AI-Driven Imaging Adoption

Driver

Decreased Scan Time

Description

Studies have shown up to 4x faster scan times with AI processing tools¹.

Stakeholder Benefit*

Increased machine availability would allow imaging centers to scan a greater volume of patients

*Benefit: Gain to stakeholder resulting from increased MRI/PET usage

Driver

Increased Confidence in Scan Quality

Description

Real-time motion tracking and gating optimization, and post-processing AI tools could correct for motion artifact in MRI and PET scans

Stakeholder Benefit*

Greater scan quality would reduce the need for repeat scans and patient callbacks, minimizing unnecessary strain on imaging facilities

Movement correction would allow for roomier, less restrictive scanners, reducing patient discomfort

Driver

Enhancement of Weaker Scanners

Description

Improved accuracy and resolution may enable 1.5T magnetic field strength scanners to approach the quality of 3T scanners, which are 30%-40% more expensive^2,3.

Stakeholder Benefit*

A broadened network of capable scanners would improve patient access to minimally-invasive diagnostics.
¹NYU Langone Health NewsHub; ²Siemens Healthineers; ³LBN Medical

Critical Implication Given current capabilities, AI-driven imaging is expected to be used alongside BBMs in the near term

With an increase in AI-powered software, the ability to integrate with imaging devices, unique software features, and pricing models will help differentiate currently available options for AD

As the number of AI-powered software solutions continues to increase, so does the competition with these three areas being key components that will help differentiate products in the space

Integration

Most software offers the ability to integrate with Picture Archiving and Communication Systems (PACS), but not all are accompanied by additional stand-alone/third-party or web-based platforms that could help differentiate themselves from the competition by offering seamless user experiences

Software features

Key features like the ability to detect ARIA in patients undergoing ATT, volumetric measurements of white or grey matter, or to perform contrast weighted images, or multi-time-point or normative comparisons will also determine which software can offer the best set of features that respond to healthcare system needs

Pricing models

Accommodating pricing models can be matched to needs of institution type; for example, subscription based for large institutions or pay as you go for smaller radiology centers

With an increase in AI-powered software, the ability to integrate with imaging devices, unique software features, and pricing models will help differentiate currently available options for AD

Product	Company	Integration	Key features
Pixyl.Neuro.BV¹	Pixyl	Integration in standard reading environment (PACS), integration via AI marketplace or distribution platform, stand-alone web based	Brain volume quantification, brain segmentation, comparison with normative values, longitudinal analysis
ARIAscore structure²	ARIAMed^†	Integration in standard reading environment (PACS)	Brain tissue and anatomy segmentation, volume quantification, normative comparison, report generation, WMH detection and quantification
QyScore³	Qynapse	Integration in standard reading environment (PACS), integration via AI marketplace or distribution platform, stand-alone web-based	Automatic labeling and volumetric quantification of segmented central nervous system structures; decreases image reading variability and segmentation errors
Trace4AD⁴	DeepTrace Technologies	Stand-alone third-party application, stand-alone web-based	Provides risk (low or high) of having or progressing to AD within 24 months by an automatic reading of the subject’s brain grey matter obtained from a 3D structural T1-weighted MRI brain study, also in combination with subject’s neuropsychological measures

Product Capabilities

Product	Detection/diagnosis	Prognosis	Monitoring	ARIA detection
Pixyl.Neuro.BV¹
ARIAscore structure²
QyScore³
Trace4AD⁴

FDA Clearance and Pricing

Product	Company	FDA clearance date	Key features	Pricing model
SubtlePET¹	Subtle Medical	12/5/2018	SubtlePET image processing software reduces noise to increase image quality using a deep neural network-based algorithm; “denoises images conducted in 25% of the original scan duration”	Unknown
Neurocloud PET²	Qubiotech	Not yet (CE certified, Class I)	Identify and quantify regions with abnormal metabolism, positive/negative amyloid result, customizable report	Pay-per-use, Subscription, Customizable Plans
Neurophet SCALE PET³	Neurophet	08/05/2022	Quantifies SUVR of biomarkers (e.g., amyloid, tau) targeted by various radiotracers using PET images; Accurately measures atrophy of white matter and grey matter caused by neurodegenerative disorders to provide analysis results and SUVR calculation for 91 brain regions	Subscription, one-off payment; based on pay-per-scan
PalRe™⁴	PAIRE	Unknown	Supports decision-making by detecting and segmenting lesions on PET scans to extract features that require attention	Unknown

Product	Noise reduction	Detection/diagnosis	Monitoring
SubtlePET¹
Neurocloud PET²
Neurophet SCALE PET³
PalRe™⁴

Detection and Monitoring

Product	Key features	Detection/diagnosis	Monitoring
Neurocloud PET³	Identify and quantify regions with abnormal metabolism, positive/negative amyloid result, customizable report
Neurophet SCALE PET⁴	Quantifies SUVR of biomarkers (e.g., amyloid, tau) targeted by various radiotracers using PET images; Accurately measures atrophy of white matter and grey matter caused by neurodegenerative disorders to provide analysis results and SUVR calculation for 91 brain regions

ARIA Detection Capabilities

Product	Key features	ARIA detection
Neurophet AQUA AD¹	Brain region segmentation, volume quantification, normative comparison, report generation, white matter hyperintensity quantification, multi-time-point analysis, ARIA monitoring
icobrain aria²	Automated quantification of ARIA-E and ARIA-H

Key Benefits

Faster Results

Objective and Comparative Analysis

Improved Accuracy of Diagnosis

Comprehensive and Organized Reporting

Methods for Tracking Disease Progression

Standardization

OSET 2024: The All-in-One Ortho Industry Meeting

Posted on October 7, 2024 by Masha Dumanis

OSET 2024: The All-in-One Ortho Industry Meeting
Event Recap and Key Takeaways
By Masha Dumanis, Senior VP

This year the Orthopaedic Summit for Evolving Techniques (OSET) welcomed its most diverse set of faculty and attendees and hosted sessions across 14 different subspecialties and groups in addition to its inaugural Investor Day hosted by Healthpoint Capital and its Business of Medicine course. Over 6 days at the incomparable Fontainebleau Hotel, Las Vegas, attendees got to participate in nonstop morning to night learning and unprecedented networking opportunities. What was abundantly clear is that there was a definitive desire among physicians to cross-pollinate with their peers and counterparts across specialties.
This year’s joint Spino-Pelvic course and joint Trauma-Shoulder sessions were very well received. OSET also broke down barriers as it welcomed both podiatric surgeons and foot and ankle orthopedists to its Foot and Ankle sessions. What makes this meeting truly unique for those who have not attended is its intentionality in bringing together industry with clinicians to further innovation in the industry.
Attendees also got to hear moving keynotes – stories of triumph, of overcoming hardships, and of celebrating the spirit of healthcare from Trina Spear, founder of FIGS scrubs, tennis legend Andre Agassi, and hockey and football heroes, Mike Eruzione and Joe Theismann.
For those who didn’t get to attend, I will share a few themes and findings:

The realities of operating in an ASC (ambulatory surgical center) – which the majority of clinicians are doing at least on a part-time basis – means doing things differently and it also means needing something different from your vendors

JnJ MedTech sponsored a panel with some of its surgeons that echoed this exact point – the importance of “finding the right partner” who can provide not just implants, but complete solutions, and understands the needs of your ASC
Clinicians touted the use of the right technologies – for instance automation for scheduling, notes dictation, and maybe even coding automation
Others advocated for simple solutions like reducing instruments, consolidating to fewer (or yes, in some cases, one) vendor(s) and various sterilization solutions – outsourcing or pods/cubes to avoid wrapping (see Turbett Surgical and SteriCUBE)
One of the powerful points made was that lots of the work that used to be done post-op is now done pre-op: patient education and communication is critical – several surgeons touted their use of Zimmer’s mymobility platform to enable this

Post-op pain management and elimination of opioids continued to be a hot topic, especially with the imminent arrival of the hard fought “NOPAIN” act which will provide separate reimbursement to qualifying treatments

In addition to Pacira and Heron, Gate Science presented on its novel RELAY technology (nerve block port and PNS device) and digital pain management with the GateKeeper app, while newcomer Synaptrix presented about its novel pre-op neuromod administration Novabloc that is slated to provide 20+ days of post op pain relief

There is an avalanche of revision surgeries coming in the next decade whose growth will far outpace the growth rate in primary joints

Solutions that address complex revisions while lowering complications and costs and improving outcomes will be highly valued, including instruments that help remove stubborn implants while being bone sparing, technologies to help rapidly diagnose and treat periprosthetic joint infections, and technologies to reduce infections (for instance, the new antibacterial coating from Onkos Surgical)
A discussion topic: Will revisions move outpatient and to ASC too? Likely yes, but a lot is necessary on the enabling side first.

On the sports medicine side, biologic augmentation has very much become a household term and there seems to be consensus that soft tissue-to-bone fixation and healing is made better by one of the now many available options (synthetics, collagen, hyaluronic acid, etc)

The indications for biologic augmentation, anecdotally, seem to be spreading beyond rotator cuff – hip/labral repair, foot and ankle/achilles repair – what fixations are not yet optimized?
Other regenerative topics included ACL repair and cartilage restoration with the MACI arthro launch, and S+N CartiHeal promotion

While Trauma doesn’t get a lot of airtime, several notable topics came up. Fragility fractures are associated with significant morbidity and mortality, and so is the standard of care – conservative treatment – for many patients, leading to death within a year.

There are new options for treatment which can get patients back to mobility and reduce pain rapidly – specifically, CurvaFix for fixation of the pelvic ring.
Additionally, surgeons discussed adjunctive treatments of IlluminOss to aid in fixation.

Across ortho – and particularly in trauma and sports medicine – compartment syndrome is a devastating complication that is both hard to catch and very invasive to treat the later it is caught.

Newcomer MY01 is bringing awareness to compartment syndrome with their minimally invasive continuous pressure monitoring technology that can reduce staff time and be limb saving – it definitely garnered a lot of interest.

The “war on technology” – whether its robotics, custom guides, or even custom implants, navigation, AR, or smart implants was ON throughout OSET – not just at this eponymous evening session, but throughout the whole conference.

As many surgeons as there were at the conference, there were equally as many opinions about the role of robotics and which robot is appropriate.
In attempting to answer whether robotics should be used in orthopedics broadly, but spine, and the ASC specifically, Dr Roland Kent turned to general robotics experts asking where robots make sense. The answer: “Robots shine in completing human tasks that require accuracy, redundancy, and reproducibility”
Arguably, we are heading in the right direction, but it’s refinement and data that may help improve the performance.
The reality is that technology continues to be more of a menu of options, rather than a need for some “death match” in which there is a conclusive winner. Surgeons not only pick what they each prefer, they often switch between technologies depending on case, setting, and patient needs.

AI was perhaps subtly or overtly a topic throughout the conference. We now have machine learning built into so many of the tools that clinicians are using and its power grows exponentially. While some scoff at AI’s potential in healthcare, I believe that we are just at the precipice of seeing its power.

Dr Isador Lieberman opened his session on the use of predictive analytics in spine with a critical point – “the decision is more important than the incision.” Today, robots are only as effective as the plan inputted by the surgeon. Similarly, cuts by a guide, or the fit of a custom implant will only be as good as the plan from the surgeon and engineer. Over the last several years this pre-operative planning demanded a completely new skill set of surgeons.
Today, aided by technology, and not just their own clinical experience, but machine learning capabilities, its facetious to say our plans are getting incrementally better. Driven by AI – our understanding of biomechanics and ability to plan cases are getting exponentially better.
AI is likely to be the tool that finally makes robotics in MSK a value-add, rather than an expensive toy that adds time.
AI will help streamline efficiency – everything from patient scheduling optimization, risk scoring and predictive analytics, and AE and readmission prevention, to improvements in treatments, and better understanding of the body’s inter-relatedness

While it seems ironic to close with the basics, there was more discussion this year on how optimizing patients’ baseline health through exercise, nutrition optimization (check out Xcelerated Recovery and Mend), and chronic disease management will have outsize impacts on outcomes in MSK

What is not as simple is that this requires coordination across sub-specialties and care-coordination tools – to steal the words of Dr Benjamin Schwartz, – what we really need is an “MSK Medical Home”
Some mechanisms that could help patients don’t exist yet – the notable clinician Dr Bob Sallis said “I can’t refer my patients to an exercise professional. Insurance pays for surgery but not personal trainers.” He went on to talk about how Kaiser has used physical activity as a “vital sign” for 15 years in its EMR and the impact on population health management
The availability of GLP-1s has helped surgeons offer actionable next steps to patients who otherwise would not have qualified for surgery

This is barely scratching the surface of all that was happening across 5-6 conference halls and the exhibit hall for six straight days (if you happen to invent something that allows me to be in multiple places at once – please call me first 😉).

To learn more about our insights on MSK, the growth in enabling tech, shifts in site of service, and more, reach out to Masha Dumanis, Senior VP and co-lead of the MedTech Practice at masha.dumanis@kxadvisors.com

Blood Biomarkers in Alzheimer’s Disease

Posted on September 25, 2024September 25, 2024 by Juan Valdez-Capuccino

Blood Biomarkers in Alzheimer’s Disease

The AD landscape is complex but evolving addressing diagnosis bottlenecks, infrastructure support/access issues, and cost considerations is crucial for improving patient outcomes.

Barriers to address for improving patient outcomes

Diagnosis

PCPs are not set up for success to provide adequate workup.
Current cognitive and functional tests have limitations and require repeat testing to detect decline over time.
Blood biomarkers (BBMs) can address some of these limitations but have had a slow uptake.

Infrastructure

Hiring and training required personnel needed to carry out all required steps for diagnosis and medication administration (e.g., staff at infusion and MRI centers).

Support/Access

Patients’ access to HCPs is limited (e.g., geographic location, HCP limited time).
Caregiver support is essential and is often overlooked when setting up patient appointments.

Cost

High cost of approved therapies is a barrier to access for patients even though they are most effective and offer cost savings when introduced early.
Other factors should be considered, such as care partners’ ability to continue working while the patient remains in the earlier stages longer.

On this page, we will provide an overview on diagnosis with a specific focus on BBMs, including the landscape, available tests, accessibility, accuracy of data, and upcoming pipeline and industry trends.

EXECUTIVE SUMMARY – THE BBM SPACE TODAY

Despite rapid expansion in BBM development, significant hurdles remain to reach broad adoption in AD¹

Challenges with Current AD Biomarker Tests^2,3

The gold standard for Aβ and tau measurements involves costly and invasive PET and CSF tests.
There is a need for less invasive and cost-effective alternatives.

BBM tests^1,2,4

Have the potential to address unmet needs because they:
- Limit the number of patients that require a confirmatory PET scan.
- Help with earlier diagnosis of AD.
Current limitations include:
- Age-dependent accuracy.
- Results influenced by comorbidities such as hypertension or CKD.

Did you know?

Because of the multiple steps in the diagnosis of AD, the average predicted wait time between clinical diagnosis and treatment is 18.6 months4
⁴.

EXECUTIVE SUMMARY – THE FUTURE BBM LANDSCAPE

Slow adoption of BBM tests is poised to shift, driven by outcomes of combination targets, greater coverage and reimbursement, and increased investments, reflecting growing confidence in BBMs in AD diagnosis.

Testing for multiple targets yields the most promising outcomes

Previous BBM tests examined individual targets. Recent approvals in the market show a shift toward a stronger emphasis on simultaneously assessing various targets (i.e., Aβ and p-tau 217).

Wider insurance coverage and improved reimbursement will enhance BBM accessibility for AD diagnosis

With the emergence of DMTs, we anticipate that more BBM tests will secure CPT codes, insurance coverage, and reimbursement protocols, accelerating their adoption.

Increasing investments and strategic partnerships underscore a high level of confidence in the potential of BBM testing

These collaborations not only demonstrate a commitment to advancing BBM technologies, but also indicate a growing belief in their ability to make a meaningful impact on AD diagnosis.

Despite an initial sluggish adoption, emerging trends point toward the anticipated expansion of BBMs in clinical practice.

Detailed Findings

Amyloid beta and tau are the primary biomarkers of Alzheimer’s disease, which are currently measured via CSF or PET scans^2,5

Amyloid beta (Aβ)⁶

Plasma Aβ42/40 levels are abnormal during the presymptomatic disease stages making earlier screening and diagnosis possible.

A lower Aβ42/40 ratio corresponds to Aβ presence in the brain.

P-tau

Plasma p-tau levels are related to both the density of Aβ plaques and tau tangles.

P-tau levels increase across the AD continuum, including the asymptomatic phase in sporadic and genetic forms of AD⁷

Given the multistep nature of AD diagnosis, more accessible testing methods are needed to help with timely and accurate AD diagnosis and intervention

AD often isn’t diagnosed until a patient has progressed to the mild dementia stage of the disease⁸

About one-third of people with MCI due to AD develop AD dementia within 5 years, and each day >2000 adults may transition to moderate AD⁹

Progression past the MCI stage can lead to ineligibility for certain AD treatments¹⁰

Patient presents with suspected cognitive changes | Assess cognition with diagnostic tools sensitive to MCI and mild AD dementia (eg, MoCA, MMSE, Mini-Cog) | Use structural imaging to rule out other conditions that may cause symptoms similar to AD (eg, MRI and CT scans)

Routine screening of adults >65 or individuals with risk factors for AD could identify more patients before they progress to mild dementia.

More affordable and accessible testing could reduce time from initial cognitive changes to formal diagnosis.

Did you know? Because of the multiple steps in the diagnosis of AD, the average predicted wait time between clinical diagnosis and treatment is 18.6 months¹⁵.

Assessment via BBMs have the potential to be an important part of the path to treatment and are a growing focus area

Overview of BBMs

Drivers:

Enable earlier diagnosis for patients over 65, particularly in mild cognitive impairment (MCI) and early Alzheimer’s disease (AD)¹
Reduce misdiagnosis
Provide greater access to biomarker-based measures compared to expensive and invasive PET/CSF tests

Barriers:

Lack of regulatory approval for BBMs
BBMs should complement, not replace, clinical assessments¹⁶
High variability in disease progression among individuals with positive biomarkers¹⁷
BBMs are not yet established in clinical practice, requiring physician education

As the field’s understanding of BBM use and limitations in the AD space increases, so does the number of in-development and commercially available tests

Test	Manufacturer	Availability	Target	Accuracy Data
AD-Detect¹⁸	Quest	Available for use	Amyloid beta, p-tau181, p-tau 217	Sensitivity: 71 Specificity: 89%
PrecivityAD¹⁹	C2N	Available for use	Amyloid beta 42/40 ratio	Sensitivity: 88% Specificity: 89% Accuracy: 86%
PrecivityAD2²⁰	C2N	Available for use	Amyloid beta 42/40 and p-tau 217/np-tau 217 ratio	Sensitivity 88% Specificity 89%
ALZpathDx²¹	ALZpath	Available for use	Amyloid beta and p-tau 217	Accuracy: 92%
P-Tau 217^22,23	Mayo Clinic	Available for use	P-tau 217	Accuracy: 94%
ALZmetrix TM²⁴	PharmaKure	Completed clinical trial	Amyloid beta, α-synuclein, p-tau 181, and p-tau 217	Accuracy: 97%
Elecsys^25,26	Roche/Lilly	Ongoing clinical trials	Amyloid beta or p-tau 217	Data not yet released
LucentAD²⁷	Quanterix	Research use only	P-tau 217	Accuracy: >90%
AB42 and TTAU²⁸	Siemens Healthineers	N/A	Amyloid beta and tau	Data not yet released
ALZpath p-tau 217^29,30	Alamar	N/A	Research only	Accuracy: >90%
Equipment dependent test³¹	Fujirebio	Research use only	Amyloid beta (1-40,1-42) and tau (p-181, p-217)	N/A

Did you know?

A breakthrough device must file for FDA 510(k) clearance when there is low to moderate risk for the device and there is a legally marketed predicated device³².

Scientific evidence has driven companies to offer tests that measure both Aβ and p-tau to obtain a more accurate assessment of AD

Test	Manufacturer	CLIA certified	Availability	Target	Accuracy Data
AD-Detect¹⁸	Quest	Yes	Available for use	Amyloid beta, p-tau 181, p-tau 217	Sensitivity: 71%, Specificity: 89%
PrecivityAD¹⁹	C2N	Yes	Available for use	Amyloid beta	Sensitivity: 88%, Specificity: 89%, Accuracy: 86%
PrecivityAD2²⁰	C2N	Yes	Available for use	Amyloid beta 42/40 and p-tau 217/np-tau 217 ratio	Sensitivity 88%, Specificity 89%
Simoa^® ALZpath²¹	ALZpath, Quanterix	Yes	Available for use	P-tau 217	Accuracy: 95%
ALZmetrix TM²²	PharmaKure	N/A	Completed clinical trial	Amyloid beta, α-synuclein, p-tau 181 and p-tau 217	Accuracy: 97%
Phospho-Tau 217^22,23	Mayo Clinic	Yes	Available for use	P-tau 217	Accuracy: 94%
Elecsys^23,24	Roche/Lilly	N/A	Ongoing clinical trials	Amyloid beta or p-tau 217	Data not yet released

Earlier developed tests were primarily designed to screen for Aβ.

There has been a shift toward the development of tests screening for p-tau 217 and others that simultaneously screen for multiple markers.

C2N, ALZpath, and Quanterix, and Roche and Eli Lilly’s plasma tests for Aβ and p-tau 217 have received the FDA Breakthrough Device Designation^23-26,33.

Did you know?

The average review time for breakthrough devices with 510(k) clearance is 152 days³⁴.

Lack of insurance coverage hinders the adoption of BBMs, but the promise of expanded coverage and reimbursement in the future can spur their acceptance and use

CPT Code	Description
0206U	Neurology (Alzheimer’s disease); cell aggregation using morphometric imaging and protein kinase C-epsilon (PKCε) concentration in response to amylospheroid treatment by ELISA, cultured skin fibroblasts, each reported as positive or negative for Alzheimer’s disease DISCERN™, NeuroDiagnostics, NeuroDiagnostics
0207U	Neurology (Alzheimer’s disease); quantitative imaging of phosphorylated ERK1 and ERK2 in response to bradykinin treatment by in situ immunofluorescence, using cultured skin fibroblasts, reported as a probability index for Alzheimer’s disease DISCERN™, NeuroDiagnostics, NeuroDiagnostics
0289U	Neurology (Alzheimer’s disease); mRNA, gene expression profiling by RNA sequencing of 24 genes, whole blood, algorithm reported as predictive risk score MindX Blood Test™, MindX Sciences™ Laboratory
0346U	Beta amyloid, Aβ40 and Aβ42 by liquid chromatography with tandem mass spectrometry (LC-MS/MS), ratio, plasma QUEST AD-Detect™ Beta Amyloid 42/40 Ratio, Plasma, Quest Diagnostics
0358U	Neurology (mild cognitive impairment); analysis of β-amyloid 1-42 and 1-40, chemiluminescence enzyme immunoassay, cerebral spinal fluid, reported as positive, likely positive, or negative Lumipulse^® G βAmyloid Ratio (1-42/1-40) Test, Fujirebio Diagnostics, Inc, Fujirebio Diagnostics, Inc
0361U	Neurofilament light chain, digital immunoassay, plasma, quantitative Neurofilament Light Chain (NfL), Mayo Clinic, Mayo Clinic
0393U	Neurology (e.g., Parkinson’s disease, dementia with Lewy bodies); cerebrospinal fluid (CSF), detection of misfolded α-synuclein protein by seed amplification assay, qualitative SYNTap^® Biomarker Test, Amprion Clinical Laboratory
0412U	Beta amyloid, Aβ42/40 ratio, immunoprecipitation with quantitation by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and qualitative ApoE isoform-specific proteotyping, plasma combined with age, algorithm reported as presence or absence of brain amyloid pathology PrecivityAD^® blood test, C2N Diagnostics LLC, C2N Diagnostics LLC
0443U	Neurofilament light chain (NfL), ultra-sensitive immunoassay, serum or cerebrospinal fluid (Effective 04/01/2024)
0445U	β-amyloid (Abeta42) and p-tau (181P) (pTau181), electrochemiluminescent immunoassay (ECLIA), cerebral spinal fluid, ratio reported as positive or negative for amyloid pathology Elecsys^® PhosphoTau (181P) CSF (p-tau 181) and βAmyloid (1-42) CSF II (Abeta 42) Ratio, Roche Diagnostics Operations Inc (US owner/operator)
83520	Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative; not otherwise specified
84999	Unlisted chemistry procedure [when specified as tau protein, amyloid beta peptide testing other than long form Aβ, Aβ1-42, Beta-amyloid (1-42), and Abeta42 in CSF specimen or neural thread protein biochemical testing]

Coverage & reimbursement is restricted

BBMs currently lack medical necessity status and require stronger evidence for clinical use
Due to their novelty, private insurance payers, Medicare, and Medicaid do not currently provide coverage for BBMs
BBM test manufacturers are actively pursuing reimbursement for their products

BBM CPT codes are limited

Only 2 BBM tests currently have corresponding CPT codes^35,36

High OOP Costs for tests

Patients need to pay out-of-pocket for biomarker tests since they are not covered by insurance
The cost per test varies by manufacturer; the QUEST-AD Detect test is priced at $399 plus a physician service fee, while the PrecivityAD test costs approximately $1,200^37-39
C2N Diagnostics emphasizes potential cost savings of $643 per identified case of Alzheimer’s disease

The use of BBMs to detect and diagnose Alzheimer’s disease early could lead to an increase in the number of patients receiving potentially life-changing treatment.

BBMs can have a significant impact on the diagnosis and monitoring of Alzheimer’s disease, benefiting both patients and physicians, if current challenges are overcome by:

Allowing for patient identification at the PCP level

Detecting patients in the earliest stages of AD

Limiting the need for a confirmatory PET scan

Leading to early intervention, maximizing the effectiveness of approved therapies

Reducing the burden on caregivers

BBM tests have the potential to shape the AD neurodiagnostic landscape⁴⁶

When used in combination with clinical and cognitive evaluation, the role of BBM in clinical practice may assist in diagnosis/prognosis and in monitoring changes related to the disease-modifying treatment, supporting the safe and effective use of treatment in the future, while PET/MRI is expected to only be necessary for borderline BBM measures.

While BBM tests are not ready to be a stand-alone diagnostic in any clinical setting, more research and clinical trials may improve these tests to the point where they can be widely used to screen for AD risk.

BBM tests, along with diagnosis dynamics and advances in screening, could change the way AD is detected, resulting in earlier detection and improved patient outcomes.

References

Yu M. Presented at the American Academy of Neurology. April 2024. Session C5
Hampel et al. Neuron. 2023;111(18):2781-2799.
Masdeu JC. Presented at the American Academy of Neurology. April 2024. Session C5
Mielke et al. Nature Medicine. 2022;28(7):1398-1405.
Jack CR Jr. Lancet Neurol. 2010;9(1):119-28.
Hansson O et al. Alzheimers Dement. 2022;18(12):2669-2686.
Janelidze S et al. JAMA Neurol. 2021;78(11):1375-1382.
Mayo Clinic. 2023. Accessed May 13, 2024. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-stages/art-20048448.
Alzheimer’s Association. Alzheimers Dement. 2024. doi:10.1002/alz.13809.
LEQEMBI (lecanemab-irmb) [Prescribing Information]. Nutley, NJ: Eisai Inc.
Alzheimer’s Association. 2022. Accessed May 13, 2024. https://www.alz.org/alzheimers-dementia/diagnosis/medical_tests.
O’Caoimh R et al. J Alzheimers Dis. 2016;51(2):619-629.
Tariq SH et al. Am J Geriatr Psychiatry. 2006;14(11):900-910.
Usarel C et al. Int Psychogeriatr. 2019;31(2):223-229.
Liu JL, et al. RAND Corporation; 2017. https://www.rand.org/pubs/research_reports/RR2272.html.
Angioni D, et al. J Prev Alzheimers Dis. 2022;9(4):569-579.
Dubois B, et al. Alzheimers Res Ther. 2023 Oct 13;15(1):175.
MedPageToday. 2024. Accessed May 13, 2024. https://www.medpagetoday.com/neurology/alzheimersdisease/109142
C2N. 2023. Accessed May 13, 2024. https://c2n.com/news-releases/cns-precivityad-blood-test-which-identifies-amyloid-pathology-as-an-aid-to-alzheimers-disease-diagnosis-further-demonstrates-its-high-accuracy-in-newly-published-research/
Meyer MR et al. Alzheimers Dement. 2024. doi: 10.1002/alz.13764.
Ashton Nj et al. medRxiv. 2023:2023.07.11.23292493.
Mayo Clinic. 2023. Accessed May 23, 2024. www.mayocliniclabs.com/test-catalog/Overview/621635#Overview
Arranz J, et al. Diagnostic performance of plasma pTau 217, pTau 181, Ab 1-42 and Ab 1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease. Preprint. Res Sq. 2023;rs.3.rs-3725688. doi:10.21203/rs.3.rs-3725688/v1
Pharmakure. 2023. Accessed May 13, 2024. https://pharmakure.com/world-alzheimers-day-using-ai-to-diagnose-early-stages-of-the-disease-2/
Roche. 2023. Accessed May 13, 2024. https://diagnostics.roche.com/us/en/news-listing/2023/roche-collaboration-lilly-enhance-early-diagnosis-alzheimers-dis.html
FierceBiotech. 2024. Accessed May 13, 2024. https://www.fiercebiotech.com/medtech/alzheimers-blood-test-roche-eli-lilly-nabs-fda-breakthrough-tag
Quanterix. 2023. Accessed May 13, 2024. https://www.quanterix.com/press-releases/quanterix-launches-high-accuracy-p-tau-217-blood-biomarker-test-to-aid-physician-diagnosis-of-alzheimers-disease/
SIEMENS Healthineers. 2020. Accessed May 13, 2024. https://www.siemens-healthineers.com/en-us/press-room/press-releases/novartiscollaboration.html
PR Newswire. 2024. Accessed May 13, 2024. https://www.prnewswire.com/news-releases/new-study-published-in-jama-neurology-affirms-high-diagnostic-accuracy-of-alzpaths-ptau217-test-in-identifying-amyloid-and-tau-in-the-brain-302040568.html
ALAMAR Biosciences. 2024. Accessed May 13, 2024. https://alamarbio.com/alamar-biosciences-and-alzpath-inc-announce-strategic-supply-agreement-for-ptau217-antibody-to-advance-alzheimers-disease-research/
FUJIREBIO. 2024. Accessed May 13, 2024. https://www.fujirebio.com/en-us/products-solutions/neurodegenerative
Medical Device Safety and the 510(k) Clearance Process. Accessed June 6, 2024. https://www.fda.gov/medical-devices/510k-clearances/medical-device-safety-and-510k-clearance-process
C2N Diagnostics. 2024. Accessed May 13, 2024. https://c2n.com/news-releases/2019/01/29/2019-1-24-c2n-diagnostics-receives-breakthrough-device-designation-from-us-fda-for-blood-test-to-screen-for-alzheimers-disease-risk
Medical Device Academy. 2024. Accessed May 13, 2024. https://medicaldeviceacademy.com/breakthrough-device-designation/
Blue Cross Blue Shield. 2023. Accessed May 13, 2024. https://mn-policies.exploremyplan.com/portal/web/medical-policies/-/mp-200
Healthy Blue. 2024. Accessed May 13, 2024. https://provider.healthybluenc.com/dam/medpolicies/healthybluenc/active/policies/mp_pw_E001583.html
EmblemHealth. 2023. Accessed May 13, 2024. https://www.emblemhealth.com/content/dam/global/pdfs/provider/reimbursement-policies/biochemical-markers-alzheimer.pdf
Precivity. 2024. Accessed May 13, 2024. https://precivityad.com/news/study-finds-cn-diagnostics-precivityad-blood-test-provides-opportunities-for-robust-cost-savings-in-the-evaluation-of-patients-with-cognitive-impairment
Canestaro et al. Popul Health Manag. 2024. doi: 10.1089/pop.2023.0309
SIEMENS Healthineers. 2020. Accessed May 13, 2024. https://www.siemens-healthineers.com/press/releases/ms-novartis.html
Quanterix. 2022. Accessed May 13, 2024. https://www.quanterix.com/press-releases/quanterix-announces-new-agreements-with-lilly-to-advance-alzheimers-disease-diagnosis-and-treatment/
Beckman Coulter. 2023. Accessed May 13, 2024. https://www.beckmancoulter.com/about-beckman-coulter/newsroom/press-releases/2023/q3/2023-jul-17-beckman-coulter-and-fujirebio-partner-to-bolster-access-to-alzheimers-disease
Quanterix. 2023. Accessed May 13, 2024. https://www.quanterix.com/press-releases/quanterix-announces-new-agreement-to-advance-blood-based-alzheimers-disease-detection/
PR Newswire. 2024. Accessed May 13, 2024. https://www.prnewswire.com/news-releases/alamar-biosciences-and-alzpath-inc-announce-strategic-supply-agreement-for-ptau217-antibody-to-advance-alzheimers-disease-research-302075376.html
EISAI. 2024. Accessed May 13, 2024. https://www.eisai.com/news/2024/news202414.html
Schindler SE, et al. Nat Rev Neurol. 2024. doi: 10.1038/s41582-024-00977-5. Epub ahead of print.

Health Equity: The Kx Research Approach and Case Study

Posted on April 27, 2023June 13, 2023 by Evelyn Tee

Health Equity:

The Kx Research Approach and Case Study

Health Equity in Advanced Treatments

How does health equity impact advanced treatments?

Advanced healthcare treatments require patients to pass through multiple specialists or undergo significant surgical procedures. As a result, health inequities are especially salient for patients to receive adequate and timely care. Specifically, in multi-step referral processes, patients move from one specialist to another, and receive a plethora of tests at each step. With the added inequities tied to determinants of health, like access, race, socio-economic status, education, and environment, the patient journey for advanced treatments can go from complicated to unnavigable.

Research on understanding the patient journey is the first step in identifying solutions for such inequities and is a necessary element of any health equity initiative.

How do you begin health equity research and initiatives?

For companies looking to kick off health equity initiatives, start with defining a patient pathway. Doing so will help identify where general points of friction occur and set a “baseline” from which underserved peoples’ experiences may vary.

A typical patient journey goes from initial detection of disease to referrals to specialists to discussions of treatment options to the ultimate treatment a patient receives. At each point of the patient journey, patients may experience multiple inequities, layering on top of each other creating significant friction. For most diseases requiring advanced treatment (e.g., surgery, infusion treatments), patients go through four key stages, from initial identification and education to confirmation and treatment.

Even in the most efficient and straightforward cases, going through the standard care pathway to reach a specialist may take months and involve at least three different diagnostic assessments.

In the following case study, Kx explores how to conduct health equity research in advanced treatments, like surgery or biologic usage, specifically focusing on challenges faced by Black patients.

Kx Case Study: Health Equity Research Identifying Barriers to Care for Black Patients Receiving Advanced Treatments

Define the Patient Journey

In disease management, a condition may first be detected by a general practitioner (GP), who then refers the patient to a specialist. Depending on the diagnostic testing and treatment types, patients may then go through multiple other specialists before receiving an advanced treatment. These patient journeys are often complex, and serve as a baseline for understanding patient challenges in obtaining treatment.

To start, Kx defined the process that all patients typically go through, regardless of race, when receiving advanced treatments, starting with initial ID and education.

Pinpoint Provider-Identified Challenges

After exploring the patient journey in advanced treatments, Kx identified four categories of stakeholders who interact with patients:

For the highest and most immediate impact, Kx focused research on specialists (core specialists, treatment administrators, and physician extenders & staff). To tease out unconscious biases, the Kx team designed interview questions to ask not only about a practitioner’s self-identified habits, but also trends they noticed among their peers. Furthermore, with the inclusion of relevant physician extenders, Kx was able to understand challenges from multiple perspectives.

Kx found physicians are highly aware of logistical challenges related to race. Physicians noted in their practice, Black patients have been disproportionately impacted by these barriers. For example, physicians noted the work-up and test requirements prior to surgery, such as dental examinations, can cause unnecessary delay for patients needing treatment. Also, lifestyle factors like poor diet and lack of exercise may lead to comorbidities, like diabetes, that further complicate results.

Additionally, diagnostic testing is often needed for the diagnosis and long-term follow up of patients on the pathway to advanced treatment. However, comorbidities (e.g., diabetes and hypertension), which are more prevalent among Black patients, can skew diagnostic measuring and symptom identification. In the case of advanced cardiological treatments, such comorbidities have specific and direct impacts on diagnostic echocardiograms, which are used to identify disease and assess severity.

Physicians struggled to self-identify challenges in recognizing patients’ disease understanding and prioritization of their healthcare. Specialists and relevant extenders acknowledge the process-oriented limitations of short patient interactions and long wait times but advocated for their own techniques and bedside manner. Many physicians also acknowledged generalized trends in their patient populations. Specifically, 1 out of 4 physicians interviewed mentioned observations related to Black patients and lower socioeconomic status that drive initial preconceived notions.

Understand the Patient Perspective

The next step of Kx’s research process focuses on gathering perspectives from patients. In the case of non-emergent cardiac surgeries, Black patients highlighted a number of challenges centering around social determinants of health which disproportionately impact Black patients in the US.

Through conversations with patients at different points of the advanced treatment pathway, it is evident these social determinants of health not only serve as predictors for individual challenges frequently faced by Black patients, but also impact the entirety of the experience. During patient interviews, Kx was able to identify, pinpoint, and aggregate the most frequent occurrence of challenges, whether during initial detection, follow-up, referral, or treatment.

Combining it with Epidemiological Evidence

Ultimately, after understanding patient and provider perspectives, Kx was able to combine findings with epidemiological evidence about patient flow-through by race and identify where patients were facing the most significant burdens.

Moving Forward

As more advanced treatments enter the US market, healthcare access and equity for Black patients become increasingly significant. The administrative requirements and time leading up to life-changing treatments can create obstacles and delay treatment for underserved or marginalized populations. However, healthcare providers and medical manufacturers that focus on the patient pathway to lower barriers to treatment can increase penetration of novel treatments and grow their eligible patient populations.

How Kx Can Help

With our expertise, Kx Advisors can guide your team in addressing health equities and targeting underpenetrated patient populations. Our experts will analyze the patient pathway to treatment, identify obstacles, and create a strategy to operationalize a health equity initiative. To learn more about how Kx can support your Health Equity initiatives, contact Evelyn Tee at evelyn.tee@kxadvisors.com.

Contact Our Team Today

References

Ostchega Y, Fryar CD, Nwankwo T, Nguyen DT. Hypertension prevalence among adults aged 18 and over: United States, 2017–2018. NCHS Data Brief, no 364. Hyattsville, MD: National Center for Health Statistics. 2020.
Stierman B, Afful J, Carroll MD, Chen TC, Davy O, Fink S, et al. National Health and Nutrition Examination Survey 2017–March 2020 prepandemic data files— Development of files and prevalence estimates for selected health outcomes. National Health Statistics Reports; no 158. Hyattsville, MD: National Center for Health Statistics. 2021. DOI: https://dx.doi.org/10.15620/cdc:106273..
Garg S, de Lemos JA, Matulevicius SA, et al. Association of concentric left ventricular hypertrophy with subsequent change in left ventricular end-diastolic volume. Circulation: Heart Failure. 2017;10(8). doi:10.1161/circheartfailure.117.003959
Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2021. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2021.
Poverty rate by race/ethnicity. KFF. https://www.kff.org/other/state-indicator/poverty-rate-by-raceethnicity/currentTimeframe=0&sortModel=%7B%22colId%22%3A%22Location%22%2C%22sort%22%3A%22asc%22%7D. Published October 28, 2022. Accessed April 10, 2023.
Lopez C, Kim B, Sacks K. Milken Institute; 2022. https://milkeninstitute.org/sites/default/files/2022-05/Health_Literacy_United_States_Final_Report.pdf. Accessed April 10, 2023.

Evolving Considerations for Segmenting Aesthetic Practices

Posted on April 20, 2023June 13, 2023 by Bob Serrano

Evolving Considerations for Segmenting Aesthetic Practices

The global aesthetics market for product sales has more than doubled in the past 10 years, from $6B[1] to $12.5B[2]. Simultaneously, the number of US aesthetics practices has exploded to exceed 40,000[3] today. Kx Advisors has worked across many of the drivers behind this growth, including novel treatment & service offerings (e.g., non-invasive fat reduction, RF microneedling), broader consumer activation & demand (e.g., millennials, beautification in a virtual age), and strong consumer pricing power.

As US aesthetic practices grow, so does their diversity in service offerings and business models. Manufacturers’ ‘old school’ segmentation approaches for their customers included core vs. non-core, practice type & size, and location. But these elements no longer tell the full story, as competition between practices increases and their mix of treatments & consumer engagement tactics continue to evolve.

How Kx Can Help

Kx Advisors has identified four additional ‘new school’ considerations for segmenting & targeting practices based on our extensive research and expertise. Contact our aesthetics team Bob Serrano bob.serrano@kxadvisors.com, Sean Vander Linde sean.vanderlinde@kxadvisors.com & Chris Waybill chris.waybill@kxadvisors.com to explore the changing industry landscape and discover how Kx Advisors can assist in achieving your Aesthetic Medicine expansion goals.

Contact Our Team Today

References

[1] The Aesthetic Academy Sets New Standards for Medical Aesthetic Training. Business Wire. Published February 10, 2014. Accessed April 18, 2023. https://www.businesswire.com/news/home/20140210005308/en/THE-Aesthetic-Academy-Sets-New-Standards-for-Medical-Aesthetic-Training

[2] Medical Insight. miinews.com. Accessed April 18, 2023. https://miinews.com/about

[3] Revance. Investor Presentation. https://investors.revance.com/static-files/3d765f7c-1d06-49ae-bac4-0fa4cf46a092. Published March 2023.

Alzheimer’s Disease Therapeutics and Diagnostics – Parallel Advancements for Patient Care

Posted on April 20, 2023June 13, 2023 by Bob Serrano

Alzheimer’s Disease Therapeutics and Diagnostics – Parallel Advancements for Patient Care

2023 has already been a landmark year in Alzheimer’s disease (AD) therapeutics: lecanemab (Leqembi), co-developed by Biogen and Eisai, received FDA accelerated approval in January, and Phase 3 results for donanemab (Eli Lilly) are expected in 2Q23, with submission for FDA full approval shortly thereafter (accelerated approval was rejected in January). With the potential for widespread availability of novel treatments in the coming years, enabling timely, accurate diagnosis of Alzheimer’s disease should be front of mind for commercial strategy teams. Alzheimer’s complexity can make early diagnosis difficult, and misdiagnosis is common¹. Fortunately, there is a burgeoning neurodiagnostics field aiming to offer clinicians and patients more certainty in their condition through a variety of CLIA-certified or FDA-approved diagnostic tests. The thoughtful selection and use of neurodiagnostics in clinical trials and the larger marketplace will be critical in the coming years to enable expanded access for Alzheimer’s Disease therapeutics.

Novel AD Treatments Necessitate Improved Diagnostics

Looking at the Alzheimer’s Disease (AD) therapeutic pipeline, there are over 30 disease-modifying therapies in late-stage clinical development² with Eisai’s lecanemab (Leqembi) and Eli Lilly’s donanemab garnering the most attention. In their confirmatory phase 3 trials, both treatments included patients suffering from early symptomatic disease or mild cognitive impairment (MCI) due to AD and aim to measure an improvement from baseline in cognitive function tests using different metrics and brain amyloid plaque deposition using PET scans. Summarized in the table below, lecanemab relies on Clinical Dementia Rating scale Sum of Boxes (CDR-SB) as the primary outcome measure while donanemab utilizes the Integrated Alzheimer’s Disease Rating Scale (iADRS):

Testing Approaches for Diagnosing Alzheimer’s Disease

Test Category	Strengths	Drawbacks
Cognitive, Functional, and Behavioral Tests: Evaluate an individual’s mental abilities to identify changes in cognitive function Notable examples: Clinical Dementia Rating scale Sum of Boxes (CDR-SB); Integrated Alzheimer’s Disease Rating Scale (iADRS)	Familiar and good track record Low cost and quick administration Able to detect disease progression	Relies on HCP consistency in application and interpretation; errors are common among PCPs Relies on heterogenous clinical symptoms; CFB tests alone lead to misdiagnosis and cannot detect pre-clinical AD
Structural Brain Imaging: Segments and measures volumes of key brain structures; used for the detection of AD biomarkers Notable examples: Volumetric Magnetic Resonance Imaging (vMRI); PET scan; CT scan	Well-established for AD diagnosis, particularly PET scans Provides an objective measure Differentiates AD from other forms of dementia (such as vascular dementia and frontotemporal)	High cost and large footprint scanning machines required Not suited/accessible to primary care settings False positives; brain changes may not be indicative of AD Patient experience; potential sedation risk to achieve needed stillness
Cerebrospinal Fluid (CSF) Tests: Detection of AD biomarkers in CSF samples, such as β-amyloid, t-tau, and p-tau Notable examples: Lumipulse® Aβ42/40 assay (Fujirebio); Elecsys CSF phospho-tau181/Aβ42 assay (Roche)	Accuracy improvements (when used alongside other tests) Routine use in specialist healthcare settings Differentiates from other forms of dementia (such as Lewy body and frontotemporal)	Invasive procedure required (lumbar puncture); risk of side effects and some patients are contraindicated (e.g., anticoagulants use) Limited accessibility in primary care settings Not validated in diverse populations
Blood Tests: Detection of AD biomarkers in blood samples, such as levels of β-amyloid, tau protein and neurofilament light (NfL) protein Notable examples: PrecivityAD® (C2N Diagnostics); Quest AD-Detect (Quest Diagnostics)	Low cost Easy to administer/minimally invasive Routine across relevant healthcare settings	Currently less accurate /definitive than brain imaging or CSF analysis Requires more sensitive measurement due to low biomarker concentrations Lower specificity in later stages of AD when biomarkers are more indicative of general neurodegeneration
Genetic Testing: Detection of genetic variants associated with an increased risk of developing AD Notable examples: APOE ε4 variant (for early- and late-onset AD); PSEN1, PSEN2 and amyloid precursor protein (APP)	Identifies risk of developing AD, supporting earlier diagnosis	Limited predictive power Limited use for diagnosis of late-onset AD; no strongly associated mutations Ethical considerations; potential for psychosocial impact of test results

Both primary endpoints, CDR-SB and iADRS, diagnose behavioral symptoms rather than biomarker measurement in their scoring. CDR-SB is frequently chosen as an endpoint as it detects disease progression by assessing cognition and function in personal care, problem-solving, memory, and other functions; however, it has been criticized for its inconsistent reproducibility in detecting treatment differences.⁵ On the other hand, iADRS is argued to reliably detect disease progression and treatment effects in participants across the spectrum of disease by measuring similar cognition and function categories through a composite score of ADAS-Cog-13 and ADCS-iADL.⁵ A point of concern is that payers may require biomarker data to supplement these cognitive tests to approve access to costly AD therapy and restrict access when inconsistencies arise. Forward-thinking therapeutic developers should consider now which sources of biomarker data will remove barriers to access to therapeutics and how best to validate this ability.

Breadth of Innovation in Diagnostics Development

Recently, diagnostics companies have collaborated with key players in AD therapeutics trials by measuring inclusion criteria and endpoint biomarkers. In November, C2N Diagnostics announced the PrecivityAD test’s use in the AHEAD trial, a lecanemab extension study, as part of the inclusion criteria of quantifying elevated brain amyloid.⁶ Specifically, PrecivityAD, a blood test, satisfies the requirement to show a plasma, cerebrospinal fluid (CSF), or positive PET result predictive of intermediate or elevated amyloid before screening. Neurodiagnostics contribute to endpoint measurements as well. When Eisai presented their ClarityAD results, all the target engagement and drug activity data from a panel of fluid biomarkers- including plasma pTau-181, GFAP and NfL – were from Quanterix Corporation’s ultrasensitive Simoa assay kits.⁷ Overall, diagnostics are already useful at the clinical trial stage and may supplant less accessible and expensive gold-standard testing like amyloid PET in the future.

Outside clinical trials, the emerging neurodiagnostics landscape is rife with innovation, using various modalities testing for different biomarkers. Fujirebio’s Lumipulse Aβ42/40 and Roche’s Elecsys CSF phospho-tau181/Aβ42 assay both offer FDA approved Aβ42/40 measuring tests using cerebrospinal fluid (CSF) to assist clinicians in making diagnoses beyond clinical examination.^8,9 This advance comes at the cost of the patient’s comfort due to the invasiveness of CSF collection. Quest Diagnostics and C2N Diagnostics address this through their CLIA-certified plasma blood tests, Quest-AD and PrecivityAD respectively, whose results approximate that of amyloid PET scan findings. Will we soon see a “Test and Treat” future in AD? Not so fast. Considerable work remains before widespread clinical adoption of plasma tests can occur.¹⁰One major barrier is the lack of plasma test performance data in diverse patient populations with comorbidities like chronic kidney disease or a history of stroke that may boost AD biomarkers in the blood. Researchers also stress that CSF and plasma tests shouldn’t be used in cognitively healthy individuals since the disease has a long preclinical phase and may not manifest in the patient’s lifetime, causing undue distress and financial ramifications. All these companies face the current headwinds of defining and achieving their reimbursement strategy in an environment where therapeutic clinical utility is still evolving. The definition of coverage policies and diagnostic criteria by CMS and major commercial payers will drive the adoption and utilization of tests moving forward.

Future Challenges Facing AD Patients

It is unclear how many patients will receive the benefit of Leqembi and other anti-amyloid therapies. In April 2022, CMS effectively denied Medicare coverage of any anti-amyloid therapies, a decision they recently re-iterated after denying petitioning from the Alzheimer’s Association.¹¹Despite this, the Veteran’s Health Administration has determined it will cover access to Leqembi to veterans who fit the VHA’s criteria and the FDA label indication. In response to Aduhelm’s accelerated approval, CMS’s Chief Medical Officer left the door open to broad access if a therapeutic shows evidence of clinical benefit through the traditional full FDA approval process.¹² A decision on full approval for Leqembi is expected in July, preceded by an FDA Advisory Committee meeting scheduled for June 9^th. Once a therapeutic overcomes this hurdle, questions about clinical utility for both a therapeutic and a diagnostic will be more settled and replaced with a simple one: what diagnostic tests can help accelerate access for an AD disease-modifying therapy?

In the near future, partnerships between diagnostics companies and drug developers can make a big difference for the millions of people grappling with the impact of dementia on their health and families. Early collaborations like the one between Eisai and C2N Diagnostics in the AHEAD study may mark the beginning of new and deeper partnerships between these two fields. New therapeutics will benefit from a robust diagnostics industry helping patients get an earlier diagnosis and diagnostics manufacturers will receive wider adoption and uptake. Future joint commercial partnerships can allow caregivers and physicians to test an individual and match them to the most appropriate treatment available.

How Kx can help

We at Kx are monitoring the Alzheimer’s Disease space evolution closely and see opportunities for commercial planning teams to meet the technology of the future through concrete, forward-looking steps today. To join us and discuss further, contact Brett at brett.larson@kxadvisors.com.

Contact Our Team Today

Thank you to Jean Santos for his contributions in the development of this piece.

References

Gaugler JE, Ascher-Svanum H, Roth DL, Fafowora T, Siderowf A, Beach TG. Characteristics of patients misdiagnosed with alzheimer’s disease and their medication use: An analysis of the NACC-UDS database – BMC geriatrics. Characteristics of patients misdiagnosed with Alzheimer’s disease and their medication use: an analysis of the NACC-UDS database. https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-13-137. Published December 19, 2013. Accessed February 2, 2023.
Alzheimer’s Disease Therapeutics. https://www.alzforum.org/therapeutics/search?fda_statuses%5B%5D=851&target_types=&therapy_types=&conditions%5B%5D=145&keywords-entry=&keywords=. Accessed January 29, 2023.
Commissioner Oof the. FDA grants accelerated approval for Alzheimer’s disease treatment. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment. Accessed January 29, 2023.
Rogers MB. No accelerated approval for Donanemab. No Accelerated Approval for Donanemab. https://www.alzforum.org/news/research-news/no-accelerated-approval-donanemab. Accessed January 29, 2023.
Wessels AM, Rentz DM, Case M, Lauzon S, Sims JR. Integrated alzheimer’s disease rating scale: Clinically meaningful change estimates. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. 2022;8(1):197-210. doi:https://doi.org/10.1002/trc2.12312.
Consortium ACT. New blood test to identify people at risk of developing Alzheimer’s symptoms will be used in clinical trial aiming to prevent memory loss. New Blood Test To Identify People At Risk Of Developing Alzheimer’s Symptoms Will Be Used In Clinical Trial Aiming To Prevent Memory Loss. https://www.prnewswire.com/news-releases/new-blood-test-to-identify-people-at-risk-of-developing-alzheimers-symptoms-will-be-used-in-clinical-trial-aiming-to-prevent-memory-loss-301422214.html. Published November 11, 2021. Accessed January 29, 2023.
Quanterix’s Simoa® technology drives advances in Alzheimer’s disease research presented at 2022 clinical trials on Alzheimer’s disease (CTAD) conference. Quanterix’s Simoa Technology Drives Advances In Alzheimer’s Disease Research Presented At 2022 Clinical Trials On Alzheimer’s Disease (CTAD) Conference. https://www.quanterix.com/press-releases/quanterixs-simoa-technology-drives-advances-in-alzheimers-disease-research-presented-at-2022-clinical-trials-on-alzheimers-disease-ctad-conference/. Published December 6, 2022. Accessed January 29, 2023.
FDA permits marketing for new test to improve diagnosis of alzheimer’s disease. FDA Permits Marketing for New Test to Improve Diagnosis of Alzheimer’s Disease. https://content.govdelivery.com/accounts/USFDA/bulletins/3165b47. Published May 4, 2022. Accessed January 29, 2023.
Zinkovich C. Roche alzheimer’s Disease Cerebrospinal Fluid (CSF) assays receive FDA clearance, supporting more accurate and timely diagnosis. Roche Alzheimer’s disease Cerebrospinal Fluid (CSF) assays receive FDA clearance, supporting more accurate and timely diagnosis. https://diagnostics.roche.com/us/en/news-listing/2022/roche-alzheimers-disease-cerebrospinal-fluid-assays-receive-fda-clearance.html. Published December 8, 2022. Accessed January 29, 2023.
Rogers MB. FDA approves Fujirebio’s CSF test for ad-quest diagnostic offers plasma test. FDA Approves Fujirebio’s CSF Test for AD—Quest Diagnostic Offers Plasma Test. https://www.alzforum.org/news/community-news/fda-approves-fujirebios-csf-test-ad-quest-diagnostic-offers-plasma-test. Published May 21, 2022. Accessed January 29, 2023.
Fact sheet Medicare coverage policy for monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease. Medicare Coverage Policy for Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer’s Disease. https://www.cms.gov/newsroom/fact-sheets/medicare-coverage-policy-monoclonal-antibodies-directed-against-amyloid-treatment-alzheimers-disease. Published April 7, 2022. Accessed January 29, 2023.
Press release CMS finalizes Medicare coverage policy for monoclonal antibodies directed against amyloid for the treatment of alzheimer’s disease. CMS Finalizes Medicare Coverage Policy for Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer’s Disease. https://www.cms.gov/newsroom/press-releases/cms-finalizes-medicare-coverage-policy-monoclonal-antibodies-directed-against-amyloid-treatment. Published April 7, 2022. Accessed February 7, 2023.

Women’s Health: The Opportunity in Gynecology and Beyond

Posted on March 8, 2023June 13, 2023 by Jenna Riffell, PhD

Women’s Health: The Opportunity in Gynecology and Beyond

Women’s healthcare and FemTech are garnering increasing attention, yet unmet need remains high, leaving opportunity for investment in an area with significant white space for growth. In this article, we highlight why investment in women’s health is important, where funding gaps lie, and demonstrate the potential for growth if these markets receive sufficient research and development (R&D).

An Underfunded Area in Healthcare

Women comprise half of the population worldwide, yet the women’s health space, which Kx defines as diseases only or disproportionately affecting women, has been consistently underfunded and often disregarded.

In 2021, excluding oncology, only 2% of treatments in the development pipeline were for women’s health conditions. In the US, a recent study analyzing National Institutes of Health (NIH) funding found that 93% of diseases underfunded by the NIH disproportionately affect women, while 58% of overfunded diseases are male-dominant.¹ Lack of scientific knowledge of women’s health conditions can then make companies reluctant to develop treatments, a risky venture even when knowledge of the disease is advanced.^2,3

Case Study: Endometriosis

Endometriosis occurs in 10% of women between the ages of 15-45,4 typified by tissue similar to the uterine lining growing outside of the uterus. The resulting pain significantly decreases patients’ quality of life, negatively impacting their performance at work, personal relationships, and mental health. Diagnosis is challenging, due to low awareness of the disease and the need for a laparoscopy to make a definitive diagnosis, leaving many patients without appropriate treatment. On average, a patient with endometriosis incurs $10,000 more direct healthcare costs annually than those without, from inpatient, outpatient, and surgical treatment alongside prescription costs. Over-the-counter (OTC) pain relief medications costs are added to these fees. Furthermore, endometriosis costs the US economy over $2,000 more than the average worker in annual absence and short-term disability costs.5 Current treatment options remain limited to painkillers, laparoscopic removal of lesions, and hormonal therapies. For those contraindicated or unresponsive to these treatments, a hysterectomy remains the only option.

Currently, the most effective pharmacotherapies are Gonadotropin Releasing Hormone (GnRH) analogs, such as elagolix (Orilissa) and relugolix (Myfembree, in combination with estradiol and norethindrone acetate), which work by inducing quasi-menopause. However, side effects including bone mineral density loss, depression, and severe nausea can be detrimental to a woman’s long-term health, and have led the FDA to restrict the duration an individual can stay on the treatment to just two years.

The current pipeline looks similarly bleak. Kissie’s Linzagolix, the only treatment in Phase III, has the same GnHR mechanism of action but with greater levels of bone mineral loss compared to approved medications. Although Phase II therapies show more promise, the market remains wide open and given the high prevalence and unmet need in endometriosis, the successful development of a safe drug would likely garner high reward.

It is not just gynecological women’s health conditions that have failed to garner sufficient R&D investment to develop effective treatments. For example, Irritable Bowel Syndrome (IBS) is a chronic disease with significant patient burden with a high prevalence in women (14%), who comprise two-thirds of all IBS patients.⁶ Symptoms, which include diarrhea, constipation, and bloating, can substantially impact everyday life. Inadequate treatments only targeting symptoms and low market development have left unmet need high.

There are multiple women’s health conditions ripe for development; collectively, the opportunity is vast. In endometriosis alone, a safe treatment displacing GnRHs could see peak sales of up to $3.9bn in the US.^7-13

The Case for Investment

Some women’s health diseases that have already seen major market development offer an insight into the high potential patient value that can be unlocked with R&D and commercial investment.

Chronic migraine is one such example. Affecting 1 in 5 women vs 1 in 16 men, it is the leading cause of disability amongst young women.¹⁴ In 2009, the market was small, with US sales totaling $1.1bn.¹⁵ Treatment options were predominantly limited to triptans, an abortive class of medication that treats individual migraine episodes as and when they occur.¹⁶ Though effective, they are not preventative and are not suitable for those who suffer from more frequent episodes due to the risk of medication-overuse headaches (MOH), also known as analgesic rebound headaches.¹⁷

However, the market has since experienced explosive growth propelled by two treatment developments: the approval of AbbVie’s Botox in 2010 and, in 2018, the arrival of three calcitonin gene-related peptide (CGRP) antagonist mAbs; Aimovig (erenumab), Ajovy (freanezumab), and Emgality (galcanezumab). Both novel classes of treatment gave prescribers the tools to move away from treating the symptoms of chronic migraine, and towards preventing future episodes.

These landmark changes in the treatment paradigm resulted in a 200% increase in annual US sales in the last four years, from 2018 to 2022.¹⁵ Since 2020, newer oral CGRPs have been approved, further reducing patient burden in migraine. With these and further developments, the market is expected to continue to grow exponentially, with total annual US sales predicted to reach >$9bn by 2028.¹⁵

The high ROI within chronic migraine shows how a shift from reactively treating symptoms, as in endometriosis and IBS, to developing well-tolerated treatments targeting the underlying cause of women’s health diseases is both desperately needed and a significant upside opportunity. Multiple relatively untapped markets offer just such opportunity on this scale.

^19-30

Polycystic ovary syndrome (PCOS), a largely understudied disease that causes metabolic issues, is one example. There are no approved treatment options despite its high prevalence, significant impact on quality of life due to hirsutism, sub-fertility, and increased risk of comorbidities such as type 2 diabetes. The generics used such as combined oral contraceptives and metformin, although effective at inducing ovulation, have little impact on metabolic issues and have tolerability concerns. The development pipeline is also particularly bleak and offers limited potential to address the high unmet need.

In irritable bowel syndrome (IBS), as discussed earlier, unmet need is high with over half of patients dissatisfied with their treatment due to side effects and inadequate efficacy,¹⁸ though there are seven marketed treatments. Pipeline development is sluggish with only two drugs currently in Phase III and nine in Phase II. This slow development can largely be attributed to poor knowledge of disease pathogenesis, linked to chronic underfunding.

Conclusion

It is evident there is extensive opportunity and necessity for development in multiple women’s health conditions. Not only are these diseases often chronic and highly prevalent, but they can significantly impact patients’ long-term health outcomes and quality of life, both key for pricing potential and market access.

Unlocking the opportunity in women’s health will require development beyond R&D. To truly address high unmet need and maximize the market opportunity, pharma companies and investors should adopt a three-pronged approach:

Increasing awareness of women’s health diseases is vital. In endometriosis, for example, the average delay from symptom onset to diagnosis is 8 years, while 70% of patients with PCOS remain undiagnosed in primary care. Poor PCP awareness leads to misdiagnosis, slow referrals, and a prolonged impact on quality of life.
Improving diagnostic tools is crucial to unlocking the full patient population. Endometriosis can only be confirmed with a laparoscopy, which is both invasive and expensive to healthcare systems, and for PCOS there is no single diagnostic test, making diagnosis challenging given the wide range of presenting symptoms. Developing diagnostic biomarkers in IBS could enable treatments to target the cause rather than symptoms, drastically improving patient outcomes.
Targeting investment towards effective, safe therapies that go beyond treating symptoms is key to changing outcomes. Painkillers such as non-steroidal anti-inflammatory drugs (NSAIDs) or hormonal contraceptives are heavily relied upon, particularly in gynecological women’s conditions. However, not only are women trying to conceive unable to use hormonal contraceptives, but side effects such as headaches or nausea can be unpleasant or even life-threatening in the rare case of blood clots, leading to poor compliance rates.

How Kx can help harness the opportunity in Women’s Health

The experts at Kx Advisors help evaluate opportunities, develop strategy, prioritize pipelines, and bring new treatments in Women’s Health to market. Our unique approach combines real-world experience with qualitative and quantitative data to provide unique solutions supporting our clients’ strategic growth initiatives. To learn more about how Kx Advisors can support your goals in Women’s Health, contact Jenna Riffell at jenna.riffell@kxadvisors.com.

Contact Our Team Today

References

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Stengel G. Female Founders Are Energizing Investment in Women’s Healthcare: Expect More In 2023. Forbes. January 2023. https://www.forbes.com/sites/geristengel/2023/01/04/female-founders-are-energizing-investment-in-womens-healthcare-expect-more-in-2023. Accessed February 20, 2023.
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Shafrir AL, Farland LV, Shah DK, et al. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Practice & Research Clinical Obstetrics & Gynaecology. 2018;51:1-15. doi:10.1016/j.bpobgyn.2018.06.001
Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. Journal of Assisted Reproduction and Genetics. 2010;27(8):441-447. doi:10.1007/s10815-010-9436-1
Bontempo AC, Mikesell L. Patient perceptions of misdiagnosis of endometriosis: Results from an online national survey. Diagnosis. 2020;7(2):97-106. doi:10.1515/dx-2019-0020
Becker CM, Gattrell WT, Gude K, Singh SS. Reevaluating response and failure of medical treatment of endometriosis: A systematic review. Fertility and Sterility. 2017;108(1):125-136. doi:10.1016/j.fertnstert.2017.05.004 ages 15-64 (% of total population). https://data.worldbank.org/indicator/SP.POP.1564.TO.ZS. Published January 1, 2021. Accessed February 21, 2023
Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z. Migraine remains second among the world’s causes of disability, and first among young women: Findings from GBD2019. The Journal of Headache and Pain. 2020;21(1). doi:10.1186/s10194-020-01208-0
Evaluate Pharma. Migraine: Indication Overview. Evaluate Pharma. https://app.evaluate.com/ux/WebReport/tabbedsummarypage.aspx?itemId=631&lType=modData&compId=1019&tabId=. Published February 15, 2023. Accessed February 21, 2023.
Cameron C, Kelly S, Hsieh SC, et al. Triptans in the Acute Treatment of Migraine: A Systematic Review and Network Meta-Analysis. Headache. 2015;55 Suppl 4:221-235. doi:10.1111/head.12601
De Felice M, Ossipov MH, Wang R, et al. Triptan-induced latent sensitization: a possible basis for medication overuse headache. Ann Neurol. 2010;67(3):325-337. doi:10.1002/ana.21897
The Lancet Gastroenterology & Hepatology. Unmet needs of patients with irritable bowel syndrome. The Lancet Gastroenterology & Hepatology. 2018;3(9):587. doi:10.1016/s2468-1253(18)30236-x
Alzheimer’s Therapeutics Market Size Report, 2022-2030. https://www.grandviewresearch.com/industry-analysis/alzheimers-therapeutics-market. Published July 2022. Accessed March 3, 2023.
Acumen Research and Consulting. Irritable bowel syndrome treatment market size. https://www.globenewswire.com/en/news-release/2022/10/03/2526998/0/en/Irritable-Bowel-Syndrome-Treatment-Market-Size-is-expected-to-reach-at-USD-4-7-Billion-by-2030-registering-a-CAGR-of-9-5-Owing-to-Increasing-Incidences-of-Gastrointestinal-Disorder.html. Published October 3, 2022. Accessed March 3, 2023.
DataM Intelligence. Uterine Fibroids Treatment Market. DataMIntelligence. https://www.datamintelligence.com/research-report/uterine-fibroids-treatment-market. Published June 6, 2022. Accessed March 3, 2023.
Facts & Factors. Global demand of rheumatoid arthritis drugs market size & share to grow at a CAGR of 1.75%, expected to hit USD 70.1 billion mark by 2030 | rheumatoid arthritis drugs industry trends, Analysis & Forecast Report by FNF. Yahoo! Finance. https://finance.yahoo.com/news/global-demand-rheumatoid-arthritis-drugs-160000928.html#:~:text=In%20terms%20of%20revenue%2C%20the,growing%20cases%20of%20rheumatoid%20arthritis. Published February 2023. Accessed March 3, 2023.
Global Data. Migraine drug market size, share & trends analysis and forecast by strategic competitor assessment, market characterization, unmet needs, clinical trial mapping and implications 2020 – 2030. Market Research Reports & Consulting | GlobalData UK Ltd. https://www.globaldata.com/store/report/migraine-market-analysis/. Published February 8, 2022. Accessed March 3, 2023.
Grand View Research. Endometriosis treatment market size & trends report, 2030. Endometriosis Treatment Market Size & Trends Report, 2030. https://www.grandviewresearch.com/industry-analysis/endometriosis-treatment-market-report#:~:text=The%20global%20endometriosis%20treatment%20market%20size%20was%20estimated%20at%20USD,USD%201%2C328.89%20million%20in%202023. Published November 2022. Accessed March 3, 2023.
Mordor Intelligence. Urinary tract infection therapeutics market analysis – industry report – trends, Size & Share. Urinary Tract Infection Therapeutics Market Analysis – Industry Report – Trends, Size & Share. https://www.mordorintelligence.com/industry-reports/urinary-tract-infection-therapeutics-market#:~:text=The%20urinary%20tract%20infection%20therapeutics%20market%20was%20valued%20at%20USD,the%20forecast%20period%202022%2D2027. Accessed March 3, 2023.
Persistence Market Research. Polycystic ovary syndrome (PCOS) treatment market revenue to close value of US$ 6.31 bn with CAGR of 4.7% by 2032- persistence market research. GlobeNewswire News Room. https://www.globenewswire.com/en/news-release/2022/10/27/2542922/0/en/Polycystic-Ovary-Syndrome-PCOS-Treatment-Market-Revenue-to-close-Value-of-US-6-31-Bn-with-CAGR-of-4-7-by-2032-Persistence-Market-Research.html. Published October 27, 2022. Accessed March 3, 2023.
Alzheimer’s Association. Why does alzheimer’s disease affect more women than men? new alzheimer’s association grant will help. Alzheimer’s Disease and Dementia. https://www.alz.org/blog/alz/february_2016/why_does_alzheimer_s_disease_affect_more_women_tha. Accessed March 3, 2023.
American College of Rheumatology. Rheumatoid arthritis . https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis. Published December 2021. Accessed March 3, 2023.
Buck Louis GM, Hediger ML, Peterson CM, et al. Incidence of endometriosis by study population and Diagnostic Method: The endo study. Fertility and Sterility. 2011;96(2):360-365. doi:10.1016/j.fertnstert.2011.05.087
Butler CC, Hawking MKD, Quigley A, McNulty CAM. Incidence, severity, help seeking, and management of uncomplicated urinary tract infection: A population-based survey. British Journal of General Practice. 2015;65(639). doi:10.3399/bjgp15x686965

For Patient Engagement solutions looking for an exit, 2023 could be their year

Posted on February 15, 2023June 13, 2023 by Rachael England

For Patient Engagement solutions looking for an exit, 2023 could be their year

After a fraught 2022 that saw a significant slowdown in acquisitions from 2021’s volume and valuation highs, product companies view M&A as a potential strategy in 2023 to enhance their value proposition and achieve efficiencies of scale. Deal volume may rebound moderately from a slump in the latter half of 2022 while lower valuations are likely to result in reduced average deal size. Kx took the opportunity to validate industry signals at events in Q4 2022, gauging deal sentiment through conversations and a survey.

Amidst the record-setting number of attendees from across the healthcare ecosystem at HLTH Conference 2022, health tech leaders were abuzz with 2023 growth plans, key concerns, and areas for excitement. Kx’s Digital Health team met with dozens of solution company C-levels, corporate development, and strategy leaders who expressed one common sentiment with surprising frequency: “we are ready to do a deal, or two.”

To further gauge the Mergers & Acquisitions sentiment expressed by leaders on the show floor, in the networking lounges, and even at the puppy park, Kx surveyed over 350 HLTH attendees. The results confirmed Kx’s ingoing hypothesis: technology providers are cautiously optimistic on M&A for 2023 due to both sell- and buy-side dynamics. On the buy side, some vendors prefer inorganic growth while others view acquisition as a quicker route to enhanced offerings and improved efficiencies. On the sell side, cash constraints and the possibility of a down-round may motivate start-ups to consider an M&A exit.

Digital health leaders interpret M&A in 2023 as a potentially attractive option to augment their offerings and address the market forces that are top-of-mind concerns to their customers, including staffing shortages & provider budget shortfalls, inflation & the looming economic downturn, and increased emphasis on patient experience and engagement. Customer requirements continue to grow, demanding tangible proof of efficacy, demonstrable ROI soon after implementation, and options for meeting patient/member expectations for convenient consumer experiences. The market continues to prefer multifunctional platform options – ideally those that perform as well as individual point solutions. Vendors see the need to position themselves as an “enterprise, end-to-end” solution that reduces the burden on their customer to stitch together disparate systems & data sources and engage with their patients/members.

Vendors with aggressive product roadmaps may find that they prefer a buy-and-build approach vs. de novo build to bulk out their offerings. This is especially true for revenue-generating acquisitions with at least some penetration in the market and further expansion potential.

More specific Kx Survey findings include:

Over 83% of respondents anticipate their organization will complete at least one acquisition this year.
Of survey respondents whose organizations closed at least one deal in 2022, two-thirds anticipate no change in the size of deals while the remainder foresee a slight decrease in size
Regardless of their company’s size, respondents indicated three main acquisition drivers:
1. Nearly two-thirds indicated growth via acquisition is their organization’s preferred growth strategy;
2. 20% indicated that more favorable valuations enhance the attractiveness of pursuing an acquisition;
3. The increase in companies open to acquisition was the key motivator for the remaining 15% of respondents

Respondents view acquisitions in 2023 as a tactical opportunity to execute within their core markets or expand into a closely adjacent market rather than expanding into new markets
While many more organizations expressed intent to complete deals in 2023 vs. 2022, respondents expect the same amount of or a slight decrease in competition
One area where significant competition may arise is Patient Engagement/Digital Front Door solutions
- 80% of respondents that intend to complete an acquisition in 2023 indicate Patient Engagement and/or Digital Front Door companies as their top priority
- Solutions in Screening, Monitoring, and Diagnostics ranked first for the remaining respondents

The heightened appeal of patient engagement/digital front door capabilities can be attributed to the coalescence of several macro-environmental factors, including:

Labor shortages necessitating a shift to self-service workflows such as online scheduling;
Consumer demand for personalized digital interactions prompting the implementation of algorithm and “AI”- driven chatbots and automated messaging
CMS patient/member experience requirements encouraging streamlined intake, claims, and complaints processing tools like “digital front doors”
Reimbursement & cost savings opportunities from Remote Patient Monitoring & Hospital at Home programs impelling user-friendly mobile apps integrated with EHRs

When compared to H2 2022 deal volume, it appears the 2023 digital health market is poised for some M&A uplift. Companies intend to face the current headwinds by focusing on their core markets and driving tangible value via enhanced capabilities for end users. Time will tell whether anticipated M&A activity materializes in 2023 as digital solutions continue to evolve and their impacts drive positive clinical, financial, operational, and experiential outcomes. Either way, Kx is already looking forward to the discussions about it at the 2023 HLTH Conference puppy park.

How Kx Can Help

Is your organization considering M&A to enhance your value proposition to customers? Is the decision made and you’re ready to move forward with landscape mapping, target identification, and due diligence? Kx’s Digital Health team supports clients throughout the process with tailored solutions informed by dialogue and reinforced by data.

Want to learn more? Contact Rachael England via e-mail (rachael.england@kxadvisors.com) or LinkedIn.

Contact Our Team Today

5 Misconceptions for MedTech Market Access Strategy

Posted on October 19, 2022June 13, 2023 by Jenna Riffell, PhD

5 Misconceptions for MedTech Market Access Strategy

Market access in MedTech is a complex and rapidly evolving environment, with increasingly intense scrutiny on the costs and benefits of new technologies as the pressure on budgets increases globally. The ability to prepare for and navigate market access strategy is, now more than ever, crucial to the success of a new product, and is frequently assessed by potential partners and acquirers with the same priority as the scientific rationale or potential for favourable regulatory approval.

During the recent MedFit 2022 event in Grenoble, we discussed the most common pitfalls that may affect market access planning and strategy with leading European experts and start-up companies. Here are the top five misconceptions for market access strategy we identified.

“We want to get the approval first, then we will plan for market access”

Engagement with payers early in product development is essential. Companies should define a path to reimbursement, and understand how payers will assess their product, as early as the concept stage to use payers’ feedback to shape the technology into a marketable product and create patient and company value. Leaving engagement with payers until late in development, or after approval, can often lead companies to:

overlook crucial requirements
mistarget patient populations
fail to expectations to gain market access
fail to gain critical pricing insights to size the commercial potential

Missing the opportunity to treat payers as your sounding board can cause delays and significant restrictions in access, while timely and iterative payer engagement has the potential to speed up the development process.

“The evidence we are generating for regulators will be sufficient for our market access strategy”

Regulatory decisions are at the top of priority lists for MedTech entrepreneurs both in the US and Europe. Selection of the right pathway and preparation of required submission dossiers are time-consuming and costly and constitute a necessary condition for market access. Late-stage start-ups agree, nonetheless, that it is far from sufficient, and payers themselves corroborate this perspective. In a recent Kx Advisors study, 100% of interviewed executives for major US payers agreed going beyond the evidence required for regulatory approval is key for market access strategy. Payers increasingly require demonstration of patient value not only with differentiated clinical efficacy and safety but through increased compliance and improved patient outcomes and satisfaction. They are also seeking additional sources of data, such as real-world evidence, insurance claims, and adverse event reports. MedTech companies should plan and pre-empt these requirements by carefully designing their studies for a payer-targeted set of endpoints as early as possible and generating evidence with not only regulators but also payers in mind.

“There is an established price for devices like ours”

Existing pricing and reimbursement benchmarks provide valuable insights for market access strategy, as showing cost-effectiveness in comparison to the current standard of care is an important part of any MedTech company’s economic narrative. However, payers’ focus is shifting towards a more holistic view, with greater interest in:

improved patient outcomes
demonstrated longer-term value
ease of use
adherence to treatment
patient satisfaction

Four out of every five payers recently interviewed by Kx Advisors indicated a preference for increased value over purely lower cost of treatment and were ready to assess pricing based on a complete view of benefit for the patient and healthcare system. The approach MedTech companies take to frame, measure, and present this value becomes a tactical choice, and a key element of a broader commercialisation strategy, that should not be dismissed or made based on a simple competitive analysis.

“We will focus on a market we know and aim for broad market access”

Many MedTech companies decide to first target their home geographic market, building on their familiarity with it, knowledge of the local language and system, and network of contacts. This approach, while easier from a product development perspective, may not allow companies to fully capture their commercial potential. In conversations with Kx Advisors, start-ups with prior product launch experience highlighted the need for fast market deployment and the value of testing the product with first adopters (and getting the product paid for early on) typically outweighs the breadth of market access. The choice of the first markets in which to launch is a strategic decision, and market access becomes one of the key drivers that should be considered in careful prioritisation of the highest potential markets. Entrepreneurs should be aware of both regional (e.g., US vs EU) and intrinsic (e.g., openness to innovative technologies) differences among payers, as well as differing patient population structures and accessibility, and explore avenues that expedite first market access, such as targeting research institutions or venturing into new geographies.

“Payers are not willing to consider innovative reimbursement models”

Getting paid for innovative technologies is notoriously difficult, especially when there is no easy way to make them fit within the established market access pathways for medical devices. The emergence of digital therapies and connected health, as well as the ongoing shift towards at-home therapies accelerated by the COVID pandemic, have only made the landscape more complex. At the same time, the awareness and urgency to address these challenges is on the rise among payers. Approximately 60% of payers recently interviewed by Kx Advisors stated they are exploring value-based reimbursement options and new, alternative pricing models for medical technologies (e.g., subscriptions or device-as-a-service arrangements) will be an increasingly welcome element of future coverage decisions. Building a differentiated market access strategy that accounts for multiple possible business models and reimbursement scenarios and exploring those early with key stakeholders can allow MedTech companies to create and leverage these opportunities.

Has your commercialisation strategy ever been impacted by any of these common misconceptions? Or are you currently facing other strategic decisions that will be crucial for your MedTech company’s growth? Feel free to contact Kx Advisors for a follow-up discussion.

Contact Our Team Today

Jenna Riffell is a Managing Partner at Kx Advisors, based in London.

Przemek Czerklewicz is a Principal at Kx Advisors, based in London. During the recent MedFit Event 2022 he led an expert panel titled “Innovators’ checklist for market access”.

Using the Patient Journey to Understand Health Equity Challenges

Posted on September 29, 2022June 13, 2023 by Evelyn Tee

Health Equity: Overview of Health Systems and Patient Pathway

Unequal healthcare access among different groups leads to less preventative care, and more urgent and intensive procedures. Such disparities in access currently cost the US healthcare system approximately $320 B annually and is projected to grow to as much as $1 trillion annually in 2040[1]. In economically and socially disadvantaged communities, patients face barriers that impact their ability to receive necessary and equal care.

For life sciences companies, inequities lead to patients receiving inadequate or delayed care, and in its worst form, causes patients to miss treatment opportunities that utilize their products.

Life science companies can begin to tackle some of the drivers and determinants of health equity by using a patient-centric approach, as patients’ primary point of interaction with the healthcare system is through their providers. A closer examination of those interactions can reveal how manufacturers and medical technology companies can create initiatives to support greater equity. Examining the patient pathway can reveal specific moments when inequities “add-up” causing significant treatment drop out.

Solutions to equity barriers are not static – companies need to set themselves on a continuous path to improvement. The place to start is understanding what drives friction between patients and their own healthcare and focusing on the patient-provider interaction to identify solutions and expand their presence in underserved markets.

Barriers Arise During Patient-Provider Interactions

In order to maximize patient access and health outcomes for life science companies and manufacturers, the patient-provider interaction is key to understanding barriers to treatment. Acute analysis of these barriers is the first step to understanding where life science teams have the most influence on health equity and patient treatment access.

Barriers limiting patient-provider interaction Before a patient walks into a doctor’s office, they may already face structural and socio-economic challenges impacting their interaction with the physician and their ability to follow a treatment plan. Such barriers include a lack of insurance, lack of transportation resources, and lack of availability. For example, Black Americans were 3x more likely to report loss of health insurance during the pandemic compared to white respondents. Structural and socioeconomic challenges also drive additional comorbidities, such as obesity and hypertension[2], which may limit treatment options.
Patient perspectives and hesitancies during provider interaction When treating patients, providers interact with patient groups with differing attitudes towards the healthcare system, their diagnoses, and treatment options. For example, Black patients are more likely to mistrust the healthcare system due to long-standing racial inequalities. A nationwide poll by The Undefeated and the Kaiser Family Foundation found 7 out of 10 Black Americans say they’re treated unfairly by the healthcare system and 55% percent say they distrust it[3]. Lower trust among patients can lead to slower and less vigilant follow-up, and potentially patient drop-off from treatment. Patient groups also have varying awareness and understanding of their diagnosis due to education levels, and a patient’s perspective on the severity of a disease can be a major driver for urgency and vigilance with treatment follow-up
Provider biases and pre-conceived notions Finally, physicians can also be impacted by racial bias, impacting the delivery of healthcare to racial minorities. Studies testing implicit association among physicians have found low to moderate levels of bias against racial minorities[4], and a public health study found 32% of Black Americans have reported being discriminated against when receiving healthcare treatment[5]. Although this bias may be unintentional, implicit bias from physicians negatively impacts patient behavior. A Journal of Family Practice study found patients who felt racial discrimination in a healthcare setting were less likely to follow physician recommendations and more likely to delay care[6]. Although many healthcare curriculums have developed to increase understanding of race-based impacts, negative impacts of bias on patient outcomes remain.

How can Kx Support Your Health Equity initiatives?

Research in Health Equity can be challenging. Understanding how to create a more equitable environment, and how to support underserved populations requires a nuanced and detailed approach to research supporting such initiatives. Kx Advisors helps clients frame research challenges using the patient pathway to understand where and how health equity initiatives should be targeted. To learn more about how Kx can support your Health Equity initiatives, contact Evelyn Tee at evelyn.tee@kxadvisors.com to learn more.

Contact Our Team Today

[1] McKinsey COVID-19 Consumer Survey as of June 8, 2020
[2] Akil L, Ahmad HA. Effects of socioeconomic factors on obesity rates in four southern states and Colorado. Ethn Dis. 2011;21(1):58-62.
[3] Common Wealth Fund: Medical mistrusts among Black Americans
[4] Sabin J, Nosek BA, Greenwald A, Rivara FP. Physicians’ implicit and explicit attitudes about race by MD race, ethnicity, and gender. J Health Care Poor Underserved. 2009;20(3):896-913. doi:10.1353/hpu.0.0185
[5] NPR/Robert Wood Johnson Foundation/Harvard T.H. Chan School of Public Health, “Discrimination in America: Experiences and views of African Americans,” 2017, Figure 1.
[6] Blanchard J, Lurie N. R-E-S-P-E-C-T: patient reports of disrespect in the healthcare setting and its impact on care. J Fam Pract. 2004;53(9):721–30.

Read The 2020 Hot Indications List

The AD landscape is complex but evolving with the recent approval of amyloid-targeting therapies (ATTs), which have enabled an economy built around supporting the new unmet needs created by these therapies

Barriers to address for improving patient outcomes

Diagnosis

Integration

EXECUTIVE SUMMARY – THE AI LANDSCAPE SPACE TODAY

Current AI-powered software are designed for a broader usein neurology

Adding functionalities such as ARIA monitoring can help address some of the unmet needs created by ATTs

Did you know?

EXECUTIVE SUMMARY – THE FUTURE AI IMAGING LANDSCAPE

Detailed Report

AI imaging could be used alongside BBMs to reduce the need for CSF testing in AD; however, it is unlikely to replace CSF testing as a standalone modality in the near-term

Driver

Description

Stakeholder Benefit*

Driver

Description

Stakeholder Benefit*

Driver

Description

Stakeholder Benefit*

With an increase in AI-powered software, the ability to integrate with imaging devices, unique software features, and pricing models will help differentiate currently available options for AD

Integration

Software features

Pricing models

With an increase in AI-powered software, the ability to integrate with imaging devices, unique software features, and pricing models will help differentiate currently available options for AD

Product Capabilities

FDA Clearance and Pricing

Detection and Monitoring

ARIA Detection Capabilities

Key Benefits

The AD landscape is complex but evolving addressing diagnosis bottlenecks, infrastructure support/access issues, and cost considerations is crucial for improving patient outcomes.

Barriers to address for improving patient outcomes

Diagnosis

Infrastructure

Support/Access

Cost

EXECUTIVE SUMMARY – THE BBM SPACE TODAY

Challenges with Current AD Biomarker Tests2,3

BBM tests1,2,4

Did you know?

EXECUTIVE SUMMARY – THE FUTURE BBM LANDSCAPE

Detailed Findings

Amyloid beta and tau are the primary biomarkers of Alzheimer’s disease, which are currently measured via CSF or PET scans2,5

Amyloid beta (Aβ)6

P-tau

Given the multistep nature of AD diagnosis, more accessible testing methods are needed to help with timely and accurate AD diagnosis and intervention

Assessment via BBMs have the potential to be an important part of the path to treatment and are a growing focus area

Overview of BBMs

Drivers:

Barriers:

As the field’s understanding of BBM use and limitations in the AD space increases, so does the number of in-development and commercially available tests

Did you know?

Scientific evidence has driven companies to offer tests that measure both Aβ and p-tau to obtain a more accurate assessment of AD

Did you know?

Lack of insurance coverage hinders the adoption of BBMs, but the promise of expanded coverage and reimbursement in the future can spur their acceptance and use

Coverage & reimbursement is restricted

BBM CPT codes are limited

High OOP Costs for tests

The use of BBMs to detect and diagnose Alzheimer’s disease early could lead to an increase in the number of patients receiving potentially life-changing treatment.

The use of BBMs to detect and diagnose Alzheimer’s disease early could lead to an increase in the number of patients receiving potentially life-changing treatment.

BBMs can have a significant impact on the diagnosis and monitoring of Alzheimer’s disease, benefiting both patients and physicians, if current challenges are overcome by:

BBM tests have the potential to shape the AD neurodiagnostic landscape46

References

Health Equity:

The Kx Research Approach and Case Study

Health Equity in Advanced Treatments

How does health equity impact advanced treatments?

How do you begin health equity research and initiatives?

Kx Case Study: Health Equity Research Identifying Barriers to Care for Black Patients Receiving Advanced Treatments

Define the Patient Journey

Pinpoint Provider-Identified Challenges

Understand the Patient Perspective

Combining it with Epidemiological Evidence

Moving Forward

How Kx Can Help

References

Evolving Considerations for Segmenting Aesthetic Practices

How Kx Can Help

References

Challenges with Current AD Biomarker Tests^2,3

BBM tests^1,2,4

Amyloid beta and tau are the primary biomarkers of Alzheimer’s disease, which are currently measured via CSF or PET scans^2,5

Amyloid beta (Aβ)⁶

BBM tests have the potential to shape the AD neurodiagnostic landscape⁴⁶