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

Why Your Orphan Drug Needs A Global Market Access Strategy

Why Your Orphan Drug Needs A Global Market Access Strategy

Key Takeaways

  • An effective global market access strategy for rare diseases requires a higher degree of regional customization compared to other launch prep activities
  • While regulatory approval in first-tier US and EU markets can often translate on a global scale, as many local regulatory bodies look to FDA or EMA approval as the gold standard, local market access requirements vary significantly
  • This variation includes, among other factors:
    • Price referencing
    • Health technology assessments
    • Public vs. private payer dynamics
    • Rebates and discounts
    • Reimbursement restrictions (e.g., step-through requirements)
    • Real-world-evidence-based payment models
  • Companies must be ready to develop individual market strategies to address these country-specific challenges

Why You Need A Global Market Access Strategy

Each country poses unique challenges in developing a rare disease market access strategy. While some areas face a scattered patient population, others may face challenges such as immature physician and patient advocacy networks. Additionally, the high cost of certain drugs, like gene therapies, are handled differently by different countries. These nuances in market behaviors and structure underlie the importance of looking across the global landscape when developing a market access strategy. For US-based pharma companies, developing a comprehensive market access plan, rather than simply pivoting off a US-focused market access strategy, will ensure the long-term launch plan meets global needs and is positioned for success.

World Map Showing Why Companies Need Global Strategy

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How To Develop A Global Market Strategy

Rare disease companies need to answer complex key questions:

  1. Which markets will be targeted for launch?
  2. How much compromise in pricing is possible to gain access in global markets, particularly given reference pricing?
  3. What evidence is available or will be developed to support global market access?­

The first step in entering a market is to identify which markets offer a path to reimbursement with sufficient pricing potential. The next step is assessing your pricing flexibility, as offering a lower price than in the US or even the EU5 can increase the likelihood of reimbursement in key OUS markets. When making these assessments, identifying patient access schemes, such as named patient supply (NPS), can validate and drive demand. Once an orphan drug gains regulatory approval, companies must be prepared to work with stakeholders, such as patient advocacy groups and KOLs, to demonstrate need for the orphan drug, clinical and cost effectiveness, and drive favorable reimbursement decisions. These stakeholders are pivotal in some markets, ensuring that patients can get treatments at affordable costs throughout the duration of their treatment. As an example, in Brazil, patient advocacy groups work closely with patients to navigate court systems that enable patients to make a legislative case for drug access and coverage before national approval, including for orphan drugs (see more below). 

Rare Disease Brazil Case Study

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External Reference Pricing

External reference pricing adds significant complexity to global market access strategy as the application of referencing varies greatly among countries, including:

  • Product Applicability: categories of products for which referencing is applied, including referencing only for drugs in a specific care setting (e.g., inpatient hospital), innovative medicines for which there is no alternative available on the market, or high-cost medicines
  • Basket Composition: both the total number and specific countries selected to include in the reference basket (typically selected based on comparable GDP per capita)
  • Calculation Method: use of either an average price or selection of the lowest price of basket countries
  • Decision Process: whether used as the main systematic criterion (most common) or as supportive information only when setting a drug price
  • Re-evaluation: pricing must be re-evaluated frequently after initial price is set

In Europe, the vast majority of countries use some form of reference pricing. With reference pricing, there is increased pricing interdependence between countries. Given the high prices of orphan drugs, it is critical for rare disease companies to develop a launch sequencing strategy that factors in price referencing. This could include strategically launching first in high-priced countries without reference pricing, then focusing on lower-priced countries.

Real-World Evidence

RWE is gaining momentum globally as real-world data (RWD) sources become available—specifically electronic health records and claims data that provide a basis for evaluating outcomes. New treatment costs remain high for rare diseases, putting pressure on pharma and biotech companies to demonstrate results for premium pricing with payers. Gene therapies are especially costly due to their complexity, making RWE an ideal tool. A prime example is the AveXis-Novartis approach to payer contracting with Zolgensma, a one-time gene therapy treatment that replaces lifetime chronic therapy for patients with spinal muscular atrophy Type 1, and which launched in the US in June 2019. Gene therapies are breaking pricing norms since manufacturers are only able to generate revenue from “one-shot” treatment for each patient, and Zolgensma made waves with a US price point of $2.1M per patient—the most expensive treatment on the market as of this writing. Novartis worked with payers to establish efficacy-based reimbursement and a 5-year installment payment option to spread payment for treatment over time. With these arrangements, risk is lower for payers, who can pay $425K annually for five years and better justify a patient switch from Biogen’s Spinraza, a chronic treatment estimated to cost $4M+ over a 10-year period. Zolgensma won coverage for 90% of US commercial patients within its first full quarter on the market, with all payers taking advantage of value-based contracting; however, initial uptake of the installment-based payment system was limited.  

Similarly, in May of this year, Zolgensma received conditional approval in Europe with the “Day One” access program, which ensures the cost of patients treated before national pricing and reimbursement agreements are in place aligns with the value-based prices negotiated following clinical and economic assessments. Working within the existing pricing and local reimbursement frameworks, the “Day One” access program for EU governments and reimbursement agencies allows the company to tackle entry into markets faster and with more flexibility. This system sets up a win for each stakeholder: the patient, the health and reimbursement bodies, and AveXis-Novartis. With the Temporary Authorization for Use (ATU) program, it became immediately accessible in France and should be available in Germany shortly. 

Coverage for therapies like Zolgensma remains dependent on demonstrating values, so companies must leverage proof of value when looking to capture new patient markets. RWE and patient-reported outcomes (PROs) provide stakeholders with concrete data to inform formulary addition and clinical trial outcome endpoints.

Case Study USA

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Moving Forward

An effective global market access strategy for orphan drugs must be adaptable to different regions and their unique challenges to be effective. As companies work through the key questions outlined above to create a successful global market access strategy, tools like RWE and external reference pricing can support tackling a large range of location-specific issues.

How Kx Can Help

Our experts evaluate business opportunities, deliver top-notch expertise, and make data-driven recommendations to our healthcare clients. Kx Advisors can guide your organization through the process of developing and implementing a global market access strategy for your rare disease drug.

Contact Our Team Today

Sources

https://www.pacificbridgemedical.com/wp-content/uploads/2014/03/Orphan-Drugs-in-Asia-2017.pdf

http://info.evaluategroup.com/rs/evaluatepharmaltd/images/2014OD.pdf

https://www.europeanpharmaceuticalreview.com/article/62846/orphan-drugs-regulation-eu/

https://ec.europa.eu/health/sites/health/files/files/committee/stamp/2015-05_stamp2/5.pdf

https://www.eurordis.org/training-health-technology-assessment

https://www.rtihs.org/sites/default/files/Rare%20Disease%20Webinar%20Slides_Final%20Feb%2027.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802694/

https://www.biospace.com/article/releases/avexis-announces-innovative-zolgensma-gene-therapy-access-programs-for-us-payers-and-families/

https://www.fiercepharma.com/pharma/novartis-zolgensma-beats-data-woe-payer-resistance-strong-and-high-interest-ceo

https://www.globenewswire.com/news-release/2020/05/19/2035354/0/en/AveXis-receives-EC-approval-and-activates-Day-One-access-program-for-Zolgensma-the-only-gene-therapy-for-spinal-muscular-atrophy-SMA.html

https://mapbiopharma.com/home/2020/04/landmark-pay-for-performance-contract-agreed-in-germany/

Should You Do Market Research During COVID-19?

Should You Do Market Research During COVID-19?

Uncertainty Sparked By COVID-19

As COVID-19 upends daily life and wreaks havoc on the global economy, companies throughout the healthcare industry are adjusting their strategic plans and putting various activities on hold. Healthcare strategy, marketing, and business development leaders are wondering – is now a good time to do market research given the crisis? Should we move forward with market research studies when customers and other stakeholders are preoccupied with their circumstances? With the environment around the world changing so rapidly, will the findings of today be valuable tomorrow?

In most cases, the answer is yes; now is a good time to do market research. Actionable insights backed by research are more critical now than ever before. However, some barriers present challenges and may make certain types of research unfeasible or less attractive. To better understand how COVID-19 may impact your market research efforts, we recommend evaluating three research dimensions:

  • Who: Target Stakeholders
  • What: Insights
  • How: Methodologies

COVID-19’s Impact on Market Research

Who: Target Stakeholders

While many healthcare providers are on the frontlines of COVID-19, some specialists are experiencing procedure cancellations, office closures, or a shift to only treating essential patients. An overall decline in patient volume for many healthcare providers (HCP), especially in outpatient settings, solves a significant challenge that organizations typically face when conducting research – the accessibility of experts. Finding and recruiting quality stakeholders with relevant expertise can be challenging and time-consuming. For HCP studies, those specialists focused on outpatient treatment or inpatient specialists less involved in COVID-19 treatment like surgeons, are ideal candidates for market research due to potential increased availability with declining patient volume. Other stakeholders, including patients, payers, and industry experts, remain ideal stakeholders for upcoming studies as a result of increased availability with stay-at-home mandates. Inpatient providers and administrators treating the virus likely have limited availability to partake in market research, making studies focused on those stakeholders not ideal.

  Target Stakeholders For COVID-19 Market Research

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What: Insights

The goal of your market research is crucial in determining whether it will be successful during this pandemic. Any research focused on understanding and adapting to the epidemic can support your organization in acclimating to the evolving environment and outperforming competitors. Upstream research for products still in development can continue without significant impact, as can research to understand the general market or competitive dynamics. However, insights gleaned from research that is especially sensitive to the pandemic, like financial benchmarking or willingness to pay analysis, may not be applicable beyond this short-term timeframe and should be delayed until the global healthcare landscape settles.  

 COVID-19 Market Research Insights

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How: Methodologies

With stay-at-home orders and other social distancing mandates in place across the globe, organizations should avoid face-to-face methodologies in most instances. Due to these restrictions, virtual-friendly methods are ideal for any market research during this crisis. This could include phone interviews, online surveys, and online focus groups, which specialists are still eager to participate in. These methods tap into the rise of online engagement we are seeing during the pandemic, making recruitment easier for interviews and surveys.

COVID-19 Market Research Methods

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Moving Forward With Market Research

Although COVID-19 has derailed many aspects of our society, your organization can continue with a critical activity: market research. Modifying your strategies to the conditions of the pandemic can allow you to move forward and even collect qualitative and quantitative information more easily.

Kx Advisors, Your Partner in Strategy

Our healthcare experts can guide you through adjusting your strategy with insights gathered from market research. As data-driven decision-makers, we’re experts at designing research to inform quantitative models, developing forecasts in emerging and innovative markets, and quantifying what is challenging to quantify. We can support your organization with market research and turn the results into actionable insights.

 

Contact Our Team Today

Adapting In COVID-19: A Product Forecasting Framework

Adapting In COVID-19: A Product Forecasting Framework

Kx’s Key Takeaways For Product and Finance Teams   

  • Separate The Trough And Rebound: Modeling both the duration of the trough and the slope of the rebound, from peak COVID-19 infections to recovery, is critical to developing an accurate product forecast    
  • Layer In Regional Segmentation: Accurate forecasting requires more regional segmentation than most models demand due to the local variation in COVID-19 cases and varied government restrictions responding to the virus  
  • Expand Data Sources: Although COVID-19 is unprecedented in many respects, historical data can be used to model its impact. Utilizing a variety of data sources—analog regions that roll back restrictions earlier, patient and provider research, and prior economic downturns —can provide a valuable frame of reference to develop a more informed forecast  
  • Make It A Living, Breathing Model: With new restrictions and the medical community’s fast-paced response, it’s critical for companies to regularly monitor and update forecasting assumptions as the pandemic evolves   

COVID-19 Impacts Product Forecasting For Pharmaceutical and Medical Device Companies  

Dealing with significant evolving obstacles associated with COVID-19, businesses worldwide are adjusting their 2020 strategic plans. Pharmaceutical and medical device companies face particularly complicated hurdles, including procedure delays, office closures, and more that prevent patient access to their products. In this time of uncertainty, it’s critical to develop an informed view of future sales to establish a strategic plan and mitigate future risks to the business.  

Your Adaptable Product Forecasting Framework  

Kx Advisors created this framework to assist organizations in accurately forecasting sales during a time of high uncertainty with COVID-19. We recommend approaching the problem in two stages: the trough and the rebound. While organizations around the globe are currently in midst of the trough, understanding both stages is crucial for full-scale recovery. The questions we’ve identified for this framework can be split into three categories of barriers that COVID-19 presents: policy barriers, behavioral barriers, and economic barriers. Policy barriers are directly related to the pandemic management decisions of governments and medical associations, while behavioral barriers are driven by changes in industry competitor, physician, and patient behavior, and economic barriers are those created by changing economic conditions affecting willingness to pay.

 

COVID-19 Product Forecasting Framework Graphic Depicting Trough and Rebound

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Planning During COVID-19  

While no one can predict the future, this framework should help you gain critical insights to better project and respond to these challenges. Leveraging this tool to strategize is only step one; your product team must continually monitor the quickly evolving factors impacting the framework’s components and adjust your strategy as needed to stay ahead of the economic effect of this pandemic.  

Kx Is Here To Help  

Struggling with product forecasting during this crisis? With extensive forecasting experience, we’re experts at quantifying what is hard to quantify.  Our healthcare experts will rapidly analyze the changing field and build strategies with your team around the opportunities we identify. 

 

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Rare Diseases – Patient Advocacy

Patient Advocacy Groups (PAGs)

1 in 2 rare diseases do not have a dedicated foundation or research support group. In the US, that number translates to close to 15 million patients navigating a complex journey without a dedicated team supporting them and ultimately seeking out a life-changing treatment. As the rare disease market continues to grow and evolve, so will the focus on patient engagement and advocacy, led in part by patient advocate leaders and community patient advocacy groups (PAGs).

PAGs engage with three primary rare disease stakeholders

Caption: Patient Advocacy Groups work with stakeholders across the rare disease patient journey and can be a valuable partner to biotech companies.

Patient advocacy groups (PAGs) are at the crux of a highly complex healthcare landscape. They play a central role in connecting several stakeholders and work as liaisons between patients, physicians, biotech companies, and community leaders. Companies frequently team up with PAGs to engage patient populations and offer support – such as treatment access and care – to both patients and caregivers. Patient Advocacy Groups also work with community leaders and far-reaching KOL networks to raise disease awareness and influence legislation and / or local policy. Other valuable activities, such as patient identification, clinical trial recruitment, and R&D collaboration, also support the indispensable role of PAGs in the rare disease market.

PAGs come in different shapes and sizes

Caption: Rare disease patient advocacy groups come in all shapes and sizes, supporting patients of many rare diseases at various levels – national or global.

The patient-focused nature of the rare disease space makes working with patient advocacy groups a necessity, not an option. While many companies may know the value that comes from PAG collaboration, they may not know how to go about having these conversations and develop a successful strategy. Companies should first thoroughly understand the various roles PAGs play in crafting an effective strategy and engage with these communities. Companies can take the knowledge they gain from these conversations to raise awareness, improve quality of life, and positively transform the treatment landscape for rare diseases. PAGs can support rare disease companies…

  • …as Patient Advocates

It’s in the name: Patient Advocacy Groups, or PAGs, are there first and foremost to be advocates for patients. PAGs are very close to the patient journey and have a unique perspective on it, including unmet needs and ongoing challenges. These organizations support patients and caregivers in seeking out treatment centers, navigating complicated access pathways, and obtaining financial assistance. PAGs are direct advocates, often lobbying in the public domain and influencing regulators to improve patient access. Biotech companies should invest in long term collaborations with PAGs to create an open dialogue about how to successfully engage with patients, such as marketing tactics or educational tools. These conversations may unearth existing challenges or unmet needs for patients that companies can capitalize on and use to differentiate themselves. Insight into patient unmet needs also provides perspective on what types of services and support patients require, and new product or support offerings can be directly informed by these conversations and custom-designed to meet patient needs. Feedback on existing support services and disease challenges can help companies also refine their customer-facing strategies. 

  • …as Educational Partners

With many rare diseases lacking educational resources, PAGs are crucial to minimize gaps in disease awareness. Besides providing patient and care education, they also work closely with COEs and KOLs to disseminate information about ongoing trials and new treatments, while encouraging patients to explore their options. The ongoing campaigns and awareness efforts often culminate in policy appeals and can even shift the treatment paradigm in the long term. Companies should consider this an opportunity to educate not only patients, but physicians as well, who are navigating a complicated diagnosis landscape with many unknowns. Diagnosis remains a large gap and could bring a big payoff to companies if they are able to develop new tools or tests to increase the diagnosis rate. Companies should strategically align themselves with PAGs to demonstrate a commitment to educating and supporting the patient population – a commitment that will reap impressive benefits later down the road.

  • …as Research Partners

PAG proximity to the patient journey makes them a valuable resource in not only selecting treatments, but in developing them. Like KOLs, PAGs support clinical trials by identifying patient populations and referring patients for recruitment. Furthermore, as the voice of the patient, PAGs are pivotal in pushing novel or first-in-class therapies through the pipeline. Their firsthand experiences with patients can inform clinical trial design, from determining best-fit patient profiles to establishing trial endpoints. As mentioned earlier in this series, an early-stage collaboration can set companies up for success as they think through treatment protocols and, eventually, product commercialization. Questions around clinical trial endpoints, treatment administration, and existing treatment protocols can be very valuable when preparing for drug development and design. Working directly with patients and physicians gives companies a first-hand understanding of their customer profile and can better inform the product and its strategy.

What questions should rare disease players be asking PAGs?

Caption: How should companies guide conversations with PAGS? Companies can look for gaps in the current landscape and identify opportunities to add value to stakeholders across the care continuum.

Patient advocacy groups will always be front and center in the rare disease space, focusing on their patients and advocating for new and effective treatments. Engaging in conversations around the treatment landscape, disease challenges, and unmet needs can present companies with an opportunity to establish a trusted presence in the market. Companies should be excited to partner with these groups and do so early; loyalty within the rare disease landscape benefits all stakeholders – not just the patients.

Rare Diseases – Market Access

AN ORPHAN DRUGS JOURNEY: COMMERCIALIZING RARE DISEASE DRUGS

In this series, Kaiser will explore how rare disease drug companies can develop commercial growth strategies to succeed against the challenges of a high cost and highly specialized market.

2018 saw 91 orphan drug approvals by the FDA – nearly 3 times greater than in 2013 and the highest number of approvals yet – along with over 400 designations for the candidates in development. 2019 is expected to bring even more orphan drug approvals as more companies begin to realize R&D investments in rare diseases. Driven by high pricing potential, significant unmet needs, and favorable regulatory policy, orphan drug sales are expected to balloon to reach $262B in the next 5 years. The market continues to grow more competitive and new technologies are emerging, such as Spark Therapeutics’ Luxturna, which marks the first FDA approval in a new class of one-time gene therapy treatments targeting inherited diseases. In this environment, companies will need to shift their focus to how they can play strategically and optimize the value of their orphan therapies.

 

Caption: Orphan drug approvals are expected to reach a similar level as 2018, with new tissue agnostic cancer therapies poised for approval and increasing market opportunities for emerging gene therapies, especially those enabled by advances in CRIPSR gene-editing. Source: FDA Orphan Drugs Data

 

Caption: Orphan drug sales are expected to grow at an ~11 % CAGR over the next five (5) years and continue to gain share of the overall drug market as sales growth outpaces non-orphan drugs, despite expected introduction of newer generics and biosimilars for non-rare conditions. Source: EvaluatePharma

 

Launching an orphan drug is very different from launching a standard, non-rare disease drug. For companies to successfully commercialize rare disease drugs, they need to understand the critical differences between traditional and non-traditional (orphan) commercial models and rely on a new playbook to capture and maintain market share.

Caption: Rare disease companies face different challenges in effectively deploying their commercial budget, namely in developing the market by identifying patients, targeting leading treatment centers of excellence, and establishing KOL partnerships. 

What makes commercializing rare disease drugs different? Rare disease drug companies need to consider launch from a patient-focused mindset rather than a traditionally physician-focused one. While traditional drugs depend on physician adoption and assume widely educated and diagnosed patient populations, the opposite is true for orphan drugs. Rare disease companies will have to manage their commercial budgets very differently, focusing on patient needs and setting the stage for:

  • Targeted sales force development: In the rare disease drug space, quantity does not mean quality. Sales teams need to address patient populations specifically, ensuring they are reaching the right customers with the right messaging. Small, agile, and cross-functional commercial teams will contrast with the larger, specialized sales teams used for traditional big-name therapies.
  • Stakeholder education: Identifying the right physicians, patients, and care settings is a challenge unique to the orphan drug market. Companies should expect to develop a market where limited educational resources, physician training, and diagnostics tools regularly inhibit accurate diagnoses of patients with rare conditions. Rare disease companies must be ready to develop their markets through targeted educational efforts and be armed with a thorough understanding of the addressable space. Many rare disease companies have established one-on-one nurse case management services to provide “personalized product support” to patients with treatment information, coverage options and authorizations, financial assistance, and care navigation. Examples of these services include Alexion’s OneSource Treatment Support and Shire’s OnePath program.
  • Patient advocacy: Physicians and patient advocacy groups (PAGs) are often an essential part of care management for many patients. By sharing educational resources, helping to address financial issues, and creating awareness for patients to enroll in clinical trials, PAGs present themselves as a necessary resource not only to patients but to orphan drug companies as well.  Drug companies should strategically align themselves with these types of groups to locate and engage patients throughout the drug approval process.
  • Effective KOL partnerships: In orphan diseases, it is common for a small group of specialized physician researchers and Key Opinion Leaders (KOLs) to manage and determine treatment for a significant portion of an orphan disease population through reference centers of excellence. Companies should consider involving KOLs with late stage clinical studies to engage patients early and potentially jumpstart early access initiatives, such as compassionate use. KOLs are also valuable assets during drug development; a collaborative approach, for example via advisory boards, fosters trust and confidence in the product all the way through launch.
  • Pricing and market access: For US companies, outcomes-based pricing and value-based contracting will become a primary focus for rare disease companies moving forward. Last year, Alnylam announced a value-based selling strategy for Patisiran, an increasingly popular approach to make the high cost of these drugs more palatable. In contrast, companies launching in Europe will face challenges as the market prepares for continued high cost drug launches and a higher bar is set for outcomes in rare diseases with one or more marketed therapies.                                                 

 

Rare disease drug companies must be ready to actively engage in market development and support targeted efforts within this fragmented arena. In the next part of this series, we will understand why stakeholder education plays a critical role in market development for rare disease drug companies and how they can successfully capitalize on the opportunity despite the unique challenges it presents.