Blood Biomarkers in Alzheimer’s Disease


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 Tests2,3

  • 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 tests1,2,4

  • 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.

BBM Tests Icon

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 scans2,5

Amyloid beta (Aβ)6

Doctor Icon

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

Chart Down Icon

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

P-tau

Doctor Icon

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

Chart Down Icon

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

Doctor Icon

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

People Icon

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

Hourglass Icon

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 Icon

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

TestManufacturerAvailabilityTargetAccuracy Data
AD-Detect18QuestAvailable for useAmyloid beta, p-tau181, p-tau 217Sensitivity: 71
Specificity: 89%
PrecivityAD19C2NAvailable for useAmyloid beta 42/40 ratioSensitivity: 88%
Specificity: 89%
Accuracy: 86%
PrecivityAD220C2NAvailable for useAmyloid beta 42/40 and p-tau 217/np-tau 217 ratioSensitivity 88%
Specificity 89%
ALZpathDx21ALZpathAvailable for useAmyloid beta and p-tau 217Accuracy: 92%
P-Tau 21722,23Mayo ClinicAvailable for useP-tau 217Accuracy: 94%
ALZmetrix TM24PharmaKureCompleted clinical trialAmyloid beta, α-synuclein, p-tau 181, and p-tau 217Accuracy: 97%
Elecsys25,26Roche/LillyOngoing clinical trialsAmyloid beta or p-tau 217Data not yet released
LucentAD27QuanterixResearch use onlyP-tau 217Accuracy: >90%
AB42 and TTAU28Siemens HealthineersN/AAmyloid beta and tauData not yet released
ALZpath p-tau 21729,30AlamarN/AResearch onlyAccuracy: >90%
Equipment dependent test31FujirebioResearch use onlyAmyloid 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

TestManufacturerCLIA certifiedAvailabilityTargetAccuracy Data
AD-Detect18QuestYesAvailable for useAmyloid beta, p-tau 181, p-tau 217Sensitivity: 71%, Specificity: 89%
PrecivityAD19C2NYesAvailable for useAmyloid betaSensitivity: 88%, Specificity: 89%, Accuracy: 86%
PrecivityAD220C2NYesAvailable for useAmyloid beta 42/40 and p-tau 217/np-tau 217 ratioSensitivity 88%, Specificity 89%
Simoa® ALZpath21ALZpath, QuanterixYesAvailable for useP-tau 217Accuracy: 95%
ALZmetrix TM22PharmaKureN/ACompleted clinical trialAmyloid beta, α-synuclein, p-tau 181 and p-tau 217Accuracy: 97%
Phospho-Tau 21722,23Mayo ClinicYesAvailable for useP-tau 217Accuracy: 94%
Elecsys23,24Roche/LillyN/AOngoing clinical trialsAmyloid beta or p-tau 217Data 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 Designation23-26,33.

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 CodeDescription
0206UNeurology (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
0207UNeurology (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
0289UNeurology (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
0346UBeta 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
0358UNeurology (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
0361UNeurofilament light chain, digital immunoassay, plasma, quantitative Neurofilament Light Chain (NfL), Mayo Clinic, Mayo Clinic
0393UNeurology (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
0412UBeta 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
0443UNeurofilament light chain (NfL), ultra-sensitive immunoassay, serum or cerebrospinal fluid (Effective 04/01/2024)
0445Uβ-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)
83520Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative; not otherwise specified
84999Unlisted 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 codes35,36

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 $1,20037-39
  • 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.


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:

Patient Identification Icon

Allowing for patient identification at the PCP level

Early Detection Icon

Detecting patients in the earliest stages of AD

PET Scan Icon

Limiting the need for a confirmatory PET scan

Early Intervention Icon

Leading to early intervention, maximizing the effectiveness of approved therapies

Caregiver Burden Icon

Reducing the burden on caregivers

BBM tests have the potential to shape the AD neurodiagnostic landscape46

Diagnosis Icon

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.

Research Icon

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.

Screening Icon

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

  1. Yu M. Presented at the American Academy of Neurology. April 2024. Session C5
  2. Hampel et al. Neuron. 2023;111(18):2781-2799.
  3. Masdeu JC. Presented at the American Academy of Neurology. April 2024. Session C5
  4. Mielke et al. Nature Medicine. 2022;28(7):1398-1405.
  5. Jack CR Jr. Lancet Neurol. 2010;9(1):119-28.
  6. Hansson O et al. Alzheimers Dement. 2022;18(12):2669-2686.
  7. Janelidze S et al. JAMA Neurol. 2021;78(11):1375-1382.
  8. Mayo Clinic. 2023. Accessed May 13, 2024. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-stages/art-20048448.
  9. Alzheimer’s Association. Alzheimers Dement. 2024. doi:10.1002/alz.13809.
  10. LEQEMBI (lecanemab-irmb) [Prescribing Information]. Nutley, NJ: Eisai Inc.
  11. Alzheimer’s Association. 2022. Accessed May 13, 2024. https://www.alz.org/alzheimers-dementia/diagnosis/medical_tests.
  12. O’Caoimh R et al. J Alzheimers Dis. 2016;51(2):619-629.
  13. Tariq SH et al. Am J Geriatr Psychiatry. 2006;14(11):900-910.
  14. Usarel C et al. Int Psychogeriatr. 2019;31(2):223-229.
  15. Liu JL, et al. RAND Corporation; 2017. https://www.rand.org/pubs/research_reports/RR2272.html.
  16. Angioni D, et al. J Prev Alzheimers Dis. 2022;9(4):569-579.
  17. Dubois B, et al. Alzheimers Res Ther. 2023 Oct 13;15(1):175.
  18. MedPageToday. 2024. Accessed May 13, 2024. https://www.medpagetoday.com/neurology/alzheimersdisease/109142
  19. 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/
  20. Meyer MR et al. Alzheimers Dement. 2024. doi: 10.1002/alz.13764.
  21. Ashton Nj et al. medRxiv. 2023:2023.07.11.23292493.
  22. Mayo Clinic. 2023. Accessed May 23, 2024. www.mayocliniclabs.com/test-catalog/Overview/621635#Overview
  23. 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
  24. Pharmakure. 2023. Accessed May 13, 2024. https://pharmakure.com/world-alzheimers-day-using-ai-to-diagnose-early-stages-of-the-disease-2/
  25. Roche. 2023. Accessed May 13, 2024. https://diagnostics.roche.com/us/en/news-listing/2023/roche-collaboration-lilly-enhance-early-diagnosis-alzheimers-dis.html
  26. FierceBiotech. 2024. Accessed May 13, 2024. https://www.fiercebiotech.com/medtech/alzheimers-blood-test-roche-eli-lilly-nabs-fda-breakthrough-tag
  27. 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/
  28. SIEMENS Healthineers. 2020. Accessed May 13, 2024. https://www.siemens-healthineers.com/en-us/press-room/press-releases/novartiscollaboration.html
  29. 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
  30. 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/
  31. FUJIREBIO. 2024. Accessed May 13, 2024. https://www.fujirebio.com/en-us/products-solutions/neurodegenerative
  32. 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
  33. 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
  34. Medical Device Academy. 2024. Accessed May 13, 2024. https://medicaldeviceacademy.com/breakthrough-device-designation/
  35. Blue Cross Blue Shield. 2023. Accessed May 13, 2024. https://mn-policies.exploremyplan.com/portal/web/medical-policies/-/mp-200
  36. Healthy Blue. 2024. Accessed May 13, 2024. https://provider.healthybluenc.com/dam/medpolicies/healthybluenc/active/policies/mp_pw_E001583.html
  37. EmblemHealth. 2023. Accessed May 13, 2024. https://www.emblemhealth.com/content/dam/global/pdfs/provider/reimbursement-policies/biochemical-markers-alzheimer.pdf
  38. 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
  39. Canestaro et al. Popul Health Manag. 2024. doi: 10.1089/pop.2023.0309
  40. SIEMENS Healthineers. 2020. Accessed May 13, 2024. https://www.siemens-healthineers.com/press/releases/ms-novartis.html
  41. 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/
  42. 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
  43. Quanterix. 2023. Accessed May 13, 2024. https://www.quanterix.com/press-releases/quanterix-announces-new-agreement-to-advance-blood-based-alzheimers-disease-detection/
  44. 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
  45. EISAI. 2024. Accessed May 13, 2024. https://www.eisai.com/news/2024/news202414.html
  46. 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

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
  1. 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.
  2. 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..
  3. 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
  4. 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.
  5. 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.
  6. 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

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

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 CategoryStrengthsDrawbacks
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 diagnosisLimited 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.10 One 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.11 Despite 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 9th. 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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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

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

  1. Mirin AA. Gender disparity in the funding of diseases by the U.S. National Institutes of Health. Journal of Women’s Health. 2021;30(7):956-963. doi:10.1089/jwh.2020.8682
  2. 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.
  3. Norris J, Bousleiman R, Scolamieri A, Atsavapranee B. Healthcare Investments and exits report annual 2022. Healthcare Investments and Exits. https://www.svb.com/trends-insights/reports/healthcare-investments-and-exits?utm_source=svb&utm_medium=pr&utm_campaign=gb-2023-01-aw-tl-ag-na-lh-na&utm_content=1pr_pct_oc_na_di_na_lp_pr. Published January 2023. Accessed February 21, 2023.
  4. Endometriosis. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/endometriosis#:~:text=Endometriosis%20is%20a%20disease%20where,and%20girls%20globally%20(2). Published March 31, 2021. Accessed February 21, 2023.
  5. Soliman AH, Surrey E, Bonafede M, Nelson JK, Castelli-Haley J. Real-World Evaluation of Direct and Indirect Economic Burden Among Endometriosis Patients in the United States. Advances in Therapy. http://doi.org/10.1007/s12325-018-0667-3. Published February 15, 2018. Accessed February 24, 2023
  6. International Foundation for Gastrointestinal Disorders. IBS Facts and Statistics. About IBS. https://aboutibs.org/what-is-ibs/facts-about-ibs/#:~:text=IBS%20affects%20between%2025%20and,3%20IBS%20sufferers%20are%20male. Published April 29, 2022. Accessed March 3, 2023.
  7. Worldometer. United States population (live). Worldometer. https://www.worldometers.info/world-population/us-population/. Published February 21, 2023. Accessed February 21, 2023.
  8. Wold Bank. Population, female (% of total population) – United States. https://data.worldbank.org/indicator/SP.POP.TOTL.FE.ZS?locations=US. Published January 1, 2021. Accessed February 21, 2023.
  9. World Bank. Population ages 15-64 (% of total population). https://data.worldbank.org/indicator/SP.POP.1564.TO.ZS. Published January 1, 2021. Accessed February 21, 2023.
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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.
  16. 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
  17. 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
  18. 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
  19. Alzheimer’s Therapeutics Market Size Report, 2022-2030. https://www.grandviewresearch.com/industry-analysis/alzheimers-therapeutics-market. Published July 2022. Accessed March 3, 2023.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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
  30. 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

Rare Disease Drug Development & Commercialization Learnings, Opportunities & Debates at World Orphan Drug Congress USA 2022

The Kx team attended the World Orphan Drug Congress (WODC) in Boston, MA last week and came away energized from three days of sharing ideas, inspirational stories, and panel discussions. This event brings together the full range of stakeholders who drive and support orphan drug development, regulatory approval, treatment delivery, and patient/caregiver support services. Here we discuss a few themes we heard across meetings and presentations:

Capturing the full market potential for a new orphan drug is a challenge; diagnosis and treatment gaps add to the unmet needs a new treatment needs to address

Repeatedly, newly approved treatments for rare diseases with a strong clinical profile (i.e., safe and effective) have not achieved the degree of adoption forecasted pre-launch. Why? With humility, drug developers acknowledged their own shortcomings in not building a comprehensive ecosystem of care for target patients, their caregivers, HCPs, and payers.

Unfortunately, there is no universal go-to-market (GTM) playbook for launching a treatment in an orphan indication; however, key questions to ask when GTM planning in rare diseases in have become clear:

  • What is the daily reality and emotional state of patients and caregivers?
  • What breakpoints exist in the patient journey, and how can we address those?
  • How can barriers to delivery be mitigated through just-in-time delivery infrastructure and treatment sites creation for gene therapies?
  • How should value be measured (to ensure access and coverage continuation)?

The term “beyond the pill” is still a popular idea, but there is a need to define what that means for meeting the needs of different patient, HCP, and payer populations. By establishing trusting, longitudinal relationships with the patients, caregivers, and HCPs they strive to serve, drug developers are successfully building tailored, comprehensive GTM strategies today for the next wave of orphan drug launches, building the foundation for “beyond the pill” to be more than a catchphrase. 

Value differentiation is best achieved through focus on simple, straightforward clinical endpoints

For over a decade, rare disease treatments have seen greater flexibility from regulators on primary endpoint designations than treatments for more prevalent indications; however, we consistently heard that leniency in clinical trial design may fade. Until now, drug developers could drive endpoints selection based on early trial results and carry these through to regulatory approval reviews. As noted by Simone Boselli, Public Affairs Director, EURODIS, during one of the panel discussions, too often today these endpoints are abandoned post-approval given challenges with continued tracking in real-world settings.

Going forward, drug developers should pursue greater prospective consideration and engagement to ascertain how regulatory bodies (FDA, EMA, health technology assessment (HTA) bodies) expect data packages to be constructed. Emphasis will be placed on using clinical endpoints that are simple to compare across studies by competing developers and straightforward to extrapolate to functional benefits for patients, as well as feasible to continue to measure in the real world as drug developers aim to build a real-world evidence base. In the future, drug developers presenting unique (rather than universally accepted) clinical endpoints may run into delays or rejections, costing time, revenue, and patient access to novel treatments.

Rare disease patients desire true partnership, including greater influence over the risk tolerance decisions and transparency on drug development setbacks

Appropriately, keynote presentation sessions often included patient advocates such as Allyson Berent, COO, GeneTx*, who shared her experience from her daughter’s Angelman Syndrome (AS) diagnosis at 6 months old. When she realized there were no approved treatments for the condition, she dedicated her time and energy to pursuing an effective treatment, ultimately becoming the Chief Science Officer of Foundation for Angelman Syndrome and co-founder of GeneTx.

(*note: GeneTx was acquired by Ultragenyx on 7/19/22)

We at Kx Advisors applaud the dedication of individuals, such as Allyson Berent, who work relentlessly to bring innovative therapies to patients. Also, we are telling her story here because her asks to industry were echoed by others at WODC:

  • Further elevate patients’ voices and requests – creating an ecosystem of care requires early and frequent patient input 
  • Consider that the risk-reward tolerance when patients are desperate for a lifeline may be different than industry’s view; many felt patients should have more influence on the calculus 
  • Increase transparency of critical feedback from the FDA to drug developers when reviewing clinical results, as patients are central to progress and deserve transparency on both advancements and setbacks; this sharing rarely occurs today, and collectively holds back innovation for the sake of competitive advantage

 

How Kx Can Help

Do you want to discuss further our takeaways from the World Orphan Drug Conference? Does your organization need to address specific challenges in rare disease asset planning and launch strategy? If so, please contact Brett Larson brett.larson@kxadvisors.com or Jenna Riffell at jenna.riffell@kxadvisors.com.

Contact Our Team Today

Cell and Gene Therapy: The Next Frontier in Healthcare

Cell and Gene Therapy: The Next Frontier in Healthcare 

Executive Summary

  • Cell and gene therapies (CGTs) have become one of the most promising technology categories in biopharma with the global market expected to grow from ~$7B in 2021 to ~$58B in 2026
  • CGT treatments are broad and can be categorized into three technology approaches: 1) Cell & gene-modified cell therapies, 2) Gene therapy & genome editing, and 3) DNA & RNA therapeutics
  • The main drivers of anticipated growth of the sector are CAR-T and cell therapies in oncology as well as gene therapies targeting rare diseases
  • CGT development has accelerated with M&A and licensing deals, which have been strong over the last 5 years, in particular after FDA approvals of Luxturna and Kymriah in 2017
  • Despite significant optimism, CGT has faced a number of commercial, clinical, and regulatory hurdles that have dampened expectations in the last year

Introduction

Cell and Gene Therapy (CGT) is one of the most promising new frontiers in advanced therapies with the potential for transformational disease-modifying outcomes. As an example, Luxturna, approved by the FDA in 2017, can restore vision in children and young adults with a rare disease that would otherwise lead to blindness. The promise of CGT is potentially very broad, holding hope for treating or even reversing many currently uncurable and more common genetic diseases like hemophilia A or Parkinson’s.

Current State of Cell & Gene Therapy

Although the space is constantly expanding in breadth and application, CGTs can be grouped into three broad types of technologies: cell and gene-modified cell therapies, gene therapy and genome editing, and DNA and RNA therapeutics.

The first CGT was approved by the FDA in 2017 (Kymriah ‒ developed by Novartis and indicated for acute lymphoblastic leukemia and diffuse large B-cell lymphoma). Since then, only 17 CGTs have launched in the US through 2021.

 

Despite a relatively low market size of $7B in 2021, CGT is forecast to grow to a market size of $58B by 2026 at a 52% CAGR, compared to only 5% for small molecules and 1% for non-CGT biologics (incl. vaccines) markets. This forecast is underpinned by a growing interest in CGT with total financing in regenerative medicine doubling from ~$10 billion in 2019 to ~$20 billion in 2020, according to the Alliance for Regenerative Medicine.[i] Interest stems from Big Pharma as well as from private equity and venture capital. In 2020, 16 out of 20 largest biopharma manufacturers had CGT products in their portfolio, although CGT account for more than 20% of pipeline assets for 2 of the 16 manufacturers.[ii] Out of all private investment made in life sciences, roughly a third is directed toward CGT ($68 billion in 2021).[iii]

Approximately 46% of the cumulative worldwide sales in CGT ($70.5 billion) is expected to come from assets currently in clinical trials. Significant growth in this segment is expected to be driven by gene therapies, which account for half of the top 10 assets with the highest projected sales. These include Valoctocogene Roxaparvovec (valrox) by BioMarin and Etranacogene Dezaparvovec by uniQure, targeting Hemophilia A and B, respectively.

Overall, CGTs have accounted for just over 14% of the 63 biologics approved and marketed in the US in 2020 and 2021. In 2021, out of 130 conventional drugs and biologics approved by the FDA, only 6 were CGTs. However, the clinical-stage pipeline is very strong with 1,183 assets across all three clinical phases. Cell therapies and gene-modified cell therapies (incl. CAR-T) account for almost two thirds of the pipeline.

In evaluating CGT assets in the pipeline, there are clear patterns that emerge with respect to therapeutic areas with more substantial investment within each technology category. Cell and gene-modified cell therapy assets predominantly focus on oncology (62% of all clinical stage programs), while assets from gene therapy and genome editing, in addition to oncology, concentrate on central nervous system (CNS) and ophthalmology applications. Over a quarter of DNA and RNA therapeutics in the pipeline focus on oncology and ~10% each target CNS and GI indications.

Rare diseases make up a significant portion of clinical stage programs, in particular for gene therapy and genome editing. Almost half of gene therapy and genome editing assets in the pipeline are targeting rare diseases, while cell and gene-modified therapies focus on non-rare diseases, many of which are in oncology.

Pipeline Category Spotlight: Gene Therapy & Genome Editing

Within CGT, gene therapy and genome editing is highly diverse, as biopharma companies are pursuing a range of therapeutic area applications. The goal of gene therapy is to treat a disease by either replacing, inactivating or including new genes into cells, either inside (in vivo) or outside patient’s body (ex vivo). This process is conducted using vectors, of which viruses are the most popular form (e.g., adenovirus, adeno-associated virus, lentivirus and retrovirus). Currently, there are only two FDA-approved gene therapies (Zolgensma and Luxturna). These two gene therapies target rare diseases, but as popularity of the technology grows, it is expected that gene therapy will be used to address more common conditions such as hemophilia A or stubbornly high LDL cholesterol.

Recent Challenges

Despite significant optimism and investment, CGTs have faced substantial hurdles to approval and access, in particular for treatments with long-term or potentially lifetime efficacy. While the effects of RNA interference are transient, gene therapy treatments and gene editing therapies like CRISPR-Cas9 are intended be permanent solutions. This raises the bar for long-term data – both for regulators seeking extended safety data for approvals and payers seeking validation of long-term efficacy to justify $1-2M+ single treatment pricing.

Bluebird bio received EMA approval for two gene therapies—Zynteglo (severe beta thalassemia) and Skysona (cerebral adrenoleukodystrophy)—but subsequently exited EU operations in 2021 due to difficulties gaining payer reimbursement. Bluebird has also encountered several clinical holds and extended FDA reviews. With these hurdles, bluebird’s future is in doubt as it faces the possibility of running out of cash with its stock trading 98% below its March 2018 peak despite the potential for three gene therapy approvals in the next two years, signaling a more challenging environment than anticipated for the sector moving forward.

Cell and Gene Therapy Deals Landscape

Only a small portion of launched CGTs originated or were owned by large biopharma companies. Licensing agreements are understandably more common than acquisitions. However, the promise of CGT has led to significant large consolidator interest and investment in pipeline assets.

 

When looking at deals >$1B in value in the last two years, licensing agreements are about as frequent as M&A.

The deals landscape around CGT has been very active in the last five years as large biopharma companies look to expand capabilities in rare diseases, hematology, immunology, and oncology. Notable deals post-pandemic include Bayer acquisition of Asklepios Biopharmaceuticals (Askbio) in December 2020 for $4B ($2B upfront) to strengthen its emerging gene therapy business through its adeno-associated virus (AAV)-based technology platform and Eli Lilly adding its first gene therapy to its portfolio through the purchase of Prevail Therapeutics in January 2021 for $1B.

When looking for partners, large biopharma often evaluates particular cell and gene therapy technology potential and strategic fit of a target. Companies are often either looking to expand existing CGT capabilities (e.g., Sanofi-Translate Bio deal to strengthen Sanofi’s mRNA center of excellence), to build up a CGT portfolio (e.g., Astellas buying Audentes to develop expertise in AAV), or to access a specific technology platform (e.g. Sumitomo acquisition of Spirovant). Large biopharma is also spreading its bets and investing in early-stage biopharma companies that are looking for ways to make cell and gene therapies address a wider range of diseases, to reduce potential side effects, or to streamline the manufacturing process. One example is Takeda’s collaboration with Code Bio to develop liver-directed gene therapy using lipid nanoparticles (LNP). LNPs are an alternative to virus-based vectors that should not trigger immune response and can carry a larger load than AAV, thus enabling gene therapy to tackle disorders where a larger gene is affected.[1]

Conclusion

These are exciting times for cell and gene therapies. “These concepts are no longer the stuff of science fiction,” noted the former FDA Commissioner Scott Gottlieb. The technologies have potential for breakthrough innovations across a wide range of therapeutic areas and conditions. Some companies choose to engage by developing capabilities in-house, while many others have chosen M&A, licensing agreements, or partnership deals with smaller companies and startups. Given the plethora of investment opportunities and multiple directions in which the CGT space is currently growing, it is even more important for the overall commercial success to choose the right deal partner and the right format for collaboration.

How Kx Can Help

Our experts evaluate business opportunities, deliver top-notch expertise, and make data-driven recommendations to our healthcare clients. Kx can support your growth strategy from opportunity assessments for pipeline investment through commercialization. Contact Sean Vander Linde at sean.vanderlinde@kxadvisors.com to learn more. 

Contact Our Team Today

References

[i] Alliance for Regenerative Medicine, Annual Report 2020
[ii] Toby AuWerter, Jeff Smith and Lydia The, “Biopharma portfolio strategy in the era of cell and gene therapy,” McKinsey & Company, April 2020
[iii] Steve Kemler, Adam Lohr, “Cell & Gene Therapy Investment Outlook in 2022 & Beyond,” Feb. 21, 2022, https://www.cellandgene.com/doc/cell-gene-therapies-investment-outlook-in-beyond-0001
[1] Madeleine Armstrong, “Genetic Medicine: The Next Generation,” Evaluate Vantage, April 2022

Strategizing for Your First Drug Launch

Strategizing for Your First Drug Launch

Part 1 of Kx’s 3-part series

Introduction

“We have 12 months to either make it or break it post-launch”. This sentiment has echoed from one pharmaceutical board room to the next for years. And though it may be overused, for pre-revenue pharmaceutical companies planning to directly launch their first product, the idiom couldn’t be truer.

With increasing payer scrutiny, heightened competition in specialty drug markets, and more restrictive in-person access to HCPs due to COVID-19, achieving commercial success out of the gate is crucial for pharmaceuticals. In an analysis of 149 new drug launches, roughly 64% of drugs met or beat expectations in their launch years. Of those, 86% continued to meet or beat analyst expectations in year 2. For the drugs that missed expectations in year 1, 70% went on to miss again in year 2. Only about 30% managed to reverse course by year 3. (Deloitte, 2020). In other words, winning in Year 1 is paramount to a drug’s long-term success and ROI.

Unfortunately, drug research and development costs are on the rise (an estimated 8.5% YoY over general price inflation) (Joseph A DiMasi 1, 2016), and pre-revenue drug companies rarely have the resources and cash flow to mimic the commercial strategies of Big Pharma and legacy incumbents. Further, these “cookie-cutter” commercial strategies applied to the wrong market or product can kill a launch before it even begins. Still, there are unique competitive advantages held by commercial leaders at smaller pharmaceutical companies that cannot be matched by larger peers and incumbents:

  • The full might of your commercial team is able to focus on one product
  • Leaner organization size and operations enable nimbler post-launch commercial tactics

Kx’s blog series on Strategizing for your First Drug Launch is intended to support late-stage, pre-revenue pharmaceutical companies who are planning to directly commercialize their first product capitalize on these competitive advantages. Kx’s 3-step approach draws on concepts from academic experts such as James Collins and Jerry Porras and on our direct, real-world expertise consulting clients through launch planning. It is designed to help your company build a dynamic commercial strategy tailored to your drug:

  1. Cast a launch vision
  2. Build a brand plan and supporting operating plan around your drug
  3. Utilize a dynamic launch P&L model to refine your launch strategy to meet internal constraints

This first post in our 3-part blog series will focus on Step 1: the launch vision.

Cast a holistic launch vision with a guiding ‘north star’ and quantifiable goals before you start commercial planning

In a 1996 publication of the Harvard Business Review, James Collins and Jerry Porras asserted that “a well-conceived vision consists of two major components: core ideology and envisioned future. Core ideology, the yin in our scheme, defines what we stand for and why we exist. Yin is unchanging and complements yang, the envisioned future. The envisioned future is what we aspire to become, to achieve, to create – something that will require significant change and progress to attain” (James C. Collins, 1996). Kx agrees that the exercise of determining the core ideology of a company (i.e., its core values combined with its core purpose) should take place at a company’s inception, well before commercialization. However, because of the outsize impact a first drug launch can have on a pharmaceutical company’s holistic success, we recommend that executives revisit and repurpose three modified components of Collins’ and Porras’ framework to cast a “Launch Vision” specific to your leading asset:

1. Launch Purpose

The launch purpose should be distinct from the core purpose of a company. For instance, Pfizer’s corporate core purpose is to “deliver breakthroughs that change patients’ lives” (Pfizer, 2022). Yet, for their SARS-CoV2 vaccine launch in 2020, Pfizer consistently messaged a more focused launch purpose to “move with the same level of [timely] urgency to safely supply a high-quality vaccine around the world” (Pfizer, 2020). This launch purpose is both more specific, and also directly linked to the unique characteristics and launch environment of the drug itself. Because Pfizer launched a first-to-market vaccine, swift distribution and broad market access were necessary cornerstones of the launch to combat the pandemic.

To align on principles for the launch purpose, executives should consider a number of questions:

  • What did we set out to achieve with this drug during R&D?
  • What makes my drug unique as a product? What is my drug solving that is different?
  • What are the characteristics of the market environment into which our drug is launching?

2. Lofty Launch Goal (LLG)

It is imperative for executives to define what launch success means before fleshing out the commercial strategy. Far too often, leaders across the healthcare industry communicate that their #1 goal in launch is to “maximize revenues” or “maximize profits” when communicating to their commercial organizations and investors. But these goals are fundamentally flawed in that they are not measurable. A commercial team should have the ability to know when it has achieved its goals.

Collins and Porras specifically state that companies should define a “Big, Hairy, Audacious Goal” or BHAG that serves as the 10-year or even 30-year measurable goal for the company. They classify BHAGs into four broad categories: target, common-enemy, role-model, and internal-transformation (James C. Collins, 1996). For drug launch planning, Kx recommends developing a goal or set of goals similar to a BHAG, and typically segments these lofty launch goals (LLGs) into three buckets:

  • Financial:
    • E.g., reach $200M of US revenue by end of Year 2
    • E.g., achieve simple payback before 2025
  • Competitive
    • E.g., become the #2 drug in our indication by Year 3 of launch
    • E.g., knock off Competitor X as the #1 drug company in our target indication
  • Brand
    • E.g., become brand with highest unaided awareness among our target HCPs
    • E.g., become the Apple of our target therapeutic category
    • E.g., introduce the first premium drug to cash-pay market

3. The Vivid Description of Launch Success

The vivid description of launch success should answer the question, “what would the environment around our drug look like if we achieve our goal and fulfill our purpose”? The answer to this question could include anything related to your first drug, but typical elements may include:

  • Market & competitive position
  • Paradigm shifts in provider practices
  • Quality of relationships with prescribers
  • Brand awareness
  • Prescriber reach and conversion
  • Patient quality of life
  • Patient access to your drug

The primary utility of the vivid description is to motivate and inspire the commercial team with something tangible to which they can aspire during the strategic planning phases ahead of launch. Often even more than the LLG, it has the ability to ground the commercial organization in a common, tangible envisioned future of success.

The Launch Purpose (your “north star”) combined with the Lofty Launch Goal and Vivid Description of Success (your “finish line”) together form the holistic Launch Vision to support your commercial and executive teams throughout the pre-launch planning process. With the Launch Vision in place, commercial leadership can pivot to building out the backbone of the first drug launch strategy: the brand plan and ideal operating plan. Read more about our end-to-end launch strategy capabilities in Steps 2 and 3 of this blog series!

How Kx Advisors can support you in building your first drug’s “Launch Vision”

The “Launch Vision” stage of first drug launch planning is typically executed internally by commercial and executive leadership. However, Kx Advisors’ pharmaceutical launch excellence team supports clients during this initial phase by facilitating workshops and discussions with senior leadership, providing relevant in-market and out-of-market insights from decades of launch strategy experience, and much more. To learn more about Kx’s launch planning capabilities, contact Chris at chris.waybill@kxadvisors.com.

Contact Our Team Today

References

Deloitte. (2020, March 26). Key factors to improve drug launches. Retrieved from Deloitte Insights: https://www2.deloitte.com/us/en/insights/industry/life-sciences/successful-drug-launch-strategy.html

James C. Collins, J. I. (1996). INNOVATING TO BRING IMPORTANT NEW THERAPIES TO PATIENTS. Harvard Business Review, 65-77.

Joseph A DiMasi 1, H. G. (2016, March 21). Innovation in the pharmaceutical industry: New estimates of R&D costs. Journal of Health Economics, 1. Retrieved from Policy & Medicine: https://www.policymed.com/2014/12/a-tough-road-cost-to-develop-one-new-drug-is-26-billion-approval-rate-for-drugs-entering-clinical-de.html#:~:text=Developing%20a%20new%20prescription%20medicine,the%20Journal%20of%20Health%20Economics.

Pfizer. (2020, December 02). Pfizer and BioNTech Achieve First Authorization in the World for a Vaccine to Combat COVID-19. Retrieved from Pfizer: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-achieve-first-authorization-world

Pfizer. (2022). INNOVATING TO BRING IMPORTANT NEW THERAPIES TO PATIENTS. Retrieved from Pfizer: https://www.pfizer.com/science/research-development/breakthroughs

Using Your Product Launch Forecast as a Strategic Tool

Using Your Product Launch Forecast as a Strategic Tool 

Forecasting as a Decision-Making Tool

Too often, commercial planning teams approach revenue forecasting as a required financial exercise rather than a strategic planning activity. The highest performing teams, however, develop revenue models to drive decision-making and reinforce strategy. The forecasting process – designing the model, understanding the demand funnel, gathering insights, aligning on assumptions, and analyzing results – can drive decisions and deliver more value than the output itself. Elevating a revenue forecast to a powerful decision-making tool requires careful planning and thoughtful design considerations.

Crafting Your Product Launch Forecast to Inform Strategy

While revenue models are commonly designed to inform resource allocation, investor communications, or inventory planning, the most robust and accurate models are also designed to inform commercial strategy.  With the correct design considerations, your commercial planning team can learn more about the patient segments driving forecast value, identify opportunities in the patient journey to drive product adoption, and pinpoint the investments needed to drive share. Further, the most effective models consider multiple scenarios to plan for key unknowns.

Unfortunately, many project teams jump into forecasting with unclear objectives, insufficient data sources, or too many scenarios, and ultimately fail to develop a useful decision-making tool. Your team can avoid common modeling pitfalls by following best practices in three critical planning steps:

  1. Create the decision-making framework  
  2. Find the applicable data for the model   
  3. Define the scenarios    

Create the Decision-making Framework

The first step of any model should be aligning on the end goals (i.e., defining the decisions model will inform).  An end goal could be, for example, determining the focus and magnitude of commercial investments, evaluating strategic options in the face of a new market force, or determining supply need for a quarterly production plan. After identifying the overarching question(s), your team can determine how to approach the model.  

Your team can use the end goal to decide on the type of model. The type of model, from market share model to launch planning to production demand, determines the model’s specificity. Analyzing the structure before gathering data to ensure the model aligns with the end goal will save your team time and effort.  For example, is an annual model sufficient to calculate net revenue, or does the organization need monthly/weekly sales granularity to inform production planning? Is there a need (and reliable data) to support international country-level forecasts, or would a regional forecast be more accurate and equally actionable? Once you understand the key questions the model is answering, the desired output, and the aligned model type, your team will have the clarity to move to the next step: finding the data.     

Find the Applicable Data for the Model    

First, your team should identify and classify relevant data sources about your product and market, such as epidemiology studies, claims data sets, qualitative interviews, quantitative surveys, historical product sales, and competitor sales, among others, for input. Forecasting teams should take a “best source” approach –evaluating every assumption individually for the highest confidence source. Without pinpointing potential knowledge gaps, models can provide incorrect or incomplete information, impacting the outputs of the model, and ultimately, the launch’s success.  

If the data does not exist in the public domain or within research resources, it can often be collected. Kx specializes in designing and executing market research with key stakeholders (e.g., providers, patients, and payers) to inform quantitative forecasts.   When designing primary market research, it is important to start with the model structure and work backward to design the research to fit the model. Designing for the model’s purpose will lead to a more accurate forecast. Finally, research should be designed to enable a “living, breathing” forecast. Research approaches such as choice-based conjoint surveys can allow forecasters to simulate new market conditions as they arise and update key assumptions without conducting additional market research. 

Define the Scenarios  

After outlining the criteria for the data, the next step is to determine which scenarios need to be analyzed. Often teams will initially attempt to investigate and list all possible options, but if the model becomes too complex, it will lose its effectiveness. Instead, the best practice is to define a base case or most likely scenario. A base case typically uses a consensus estimate or confidence-based weighting along key assumptions to drive forecast outputs. Once your team identifies the most likely scenario, define the parameters you want to test. Identifying priorities and areas of uncertainty will help determine which scenarios to test. For example, breadth of market access or coverage, varying price points, the impact of future clinical study outcomes on adoption, and changes to competitor mix are some of the most frequently explored scenarios.  

How Kx Can Help With Your Product Launch Forecast

Over the last four decades, our team has developed proven modeling and forecasting approaches that produce accurate, insightful outputs and drive strategic decision making. Our team acts as strategic partners to help guide you through the entire process, including developing the product launch forecast, gathering the underlying data and insights, aligning internal stakeholders, and ultimately preparing the model for you to run.  

 

Contact Our Team Today

How Understanding Cognitive Bias Can Drive Patient Volumes

How Understanding Cognitive Bias Can Drive Patient Volumes

Understanding Patient and Healthcare Provider Behavior 

We all strive to make rational choices. But as humans, we are prone to bias and misjudgment. In the medical field, cognitive biases can have a profound impact on both patients and healthcare providers. Kx frequently conducts studies to uncover cognitive biases in referral pathways, including specialist referrals for more advanced therapies or interventions.

By pinpointing these biases, our team helps specialty drug and medical device clients focus their marketing and education efforts and increase market penetration within their eligible patient population. 

Common Dilemmas

Often specialists do not refer patients for treatment quickly enough or at all. These delays in or lack of treatment not only allow the patient’s condition to deteriorate, but also prevent the drug and device companies from fully reaching their addressable patient population. In our recent studies, Kx found that cognitive biases exist at each stage of the referral process.

Cognitive bias map of specialist referral pathway
Click to expand

 

The Kx Solution

When guiding healthcare organizations by improving their specialist referral pathway, the Kx team runs an in-depth qualitative analysis speaking with specialists to understand critical attitudes, behaviors, and beliefs across the population of relevant doctors. Key differences within demographic segments (e.g., age, specialty, practice type) and behavioral segments (e.g., willingness to refer, referral choice) help identify drivers of attitudes and potential solutions for changing these behaviors. 

Uncovering Cognitive Bias to Reach the Addressable Patient Population  

Kx developed the following key findings to drive the patients through the specialist referral pathway:

  1. Awareness that symptom recognition is often the most significant barrier in the referral process and education to combat the issue. Early in the referral process, during the diagnosis phase, cognitive biases result in the specialist not probing consistently, missing symptoms by not asking the right questions, or simply not asking enough clarifying questions. Incorrectly identifying patients’ health status based on outward appearance or insufficiently probing symptoms can result in critical underdiagnoses or undertreatment.
  2. A clear path to referral, particularly one with a singular point of contact, can help referring physicians feel more at ease. Successful drug and device companies reduce friction in referral pathways by helping referring physicians establish clear points of contact across hospitals, specialists, and surgical teams. Elucidating a single point of contact cuts down on ambiguity and removes an obstacle for referring providers.
  3. Direct relationships between the referring specialists and the treatment teams (surgery team) build comfort and encourage referrals.
  4. When creating tools for doctors, simplicity and ease of use are key factors. Biases exist among doctors to simplify complex thought processes. Though tools, like decision guides for complex cases, can be extremely beneficial, they must be simple and easy to understand and use to overcome biases and help physicians better identify which patients need further treatment.

How Kx Can Help

Our healthcare experts can guide you by adjusting various aspects of our corporate strategy, including your referral pathway, with insights from market research. Cognitive bias is built into our research methodology, enabling your team to overcome any we find and fulfill more referrals. As data-driven decision-makers, we design research using both traditional factors and behavioral science to pinpoint process improvement and qualitative analysis opportunities. 

 

Contact Our Team Today