Rare Diseases: Bridging the Gap between Drug Manufacturers and Payers

The concept of evaluating the value of pharmaceutical products is not new though the changing dynamics of the healthcare system have brought it to center stage. The days of simply determining the market demand as a function of price and choosing the revenue or profit optimizing point are gone.  An explicit rationale, also known as the “value-based price”, has become a prerequisite for enabling conversations with payers. In this context, the discipline of value demonstration becomes central to the ability to price, and the success of a new technology depends not just on clinical trial-based results and demand based pricing models, but on the explicit determination of value under expected real-world conditions. Payers, including pharmacy benefit managers (PBMs) and managed care entities, are increasingly relying on value-driven tactics to afford and manage therapy costs, especially in the rare disease space.

The EU and US define “rare diseases” differently. In the EU, a rare disease is one that effects fewer than 1 in 200 people. While in the US fewer than 200,000 people are impacted.1 According to the National Institutes of Health (NIH), there are approximately 7,000 rare diseases, and about 1 in 10 Americans will suffer from one.2  The Orphan Drug Act (ODA) of 1983 incentivized drug manufacturers to enter these difficult niche markets. Over the years, development activity in this segment has shown no sign of slowing down. In 2018 alone, the FDA approved 35 novel products with an orphan drug designation, the most since the enactment of the ODA.3 This area is estimated to continue growing and become a $242 billion global market by 2024.4

Source: Evaluate Pharma Orphan Drug Report 2019

In 2016, the median orphan drug cost per patient was $83,883.5 Today therapies can cost upwards of $400,000.6 Just recently, the most expensive therapy, Zolgensma, was launched at a record price of $2.1 million.7 As more costly orphan products come to market, payers face increasing pressures to manage these therapies. Rare diseases were once immune to management strategies due to the high unmet need, few, if any, treatment options, and small patient populations. That math, however, has changed. High prices have introduced more uncertainties from the payer perspective around the critical question: Does the medication’s value justify its price? These uncertainties have driven payers to utilize different cost containment strategies:

  • Utilization Management
    Utilization management has been the traditional go-to strategy of payers. Implementing step therapy to ensure initial use of lower cost alternatives, limiting days of medication supplied or prescriber type, and prior authorizations are standard in many different formularies and therapeutic areas. More aggressive management criteria for rare diseases are now being used. Prior authorizations, for example, may now restrict drug use to its clinical trial inclusion/exclusion criteria rather than the FDA-approved label. Renewal processes may require more disease documentation, and orphan products may experience step therapy restrictions in the event of generics or multiple options.
  • Exclusion Formularies and Value Frameworks
    Rare diseases used to be safe from formulary exclusion lists. However, that changed in 2017 with CVS Caremark’s exclusion of drugs for chronic myelogenous leukemia (CML).8 Since then, others have followed, such as Express Scripts excluding drugs for hemophilia and hereditary angioedema in 2019.9
    Payers are also increasingly considering cost-effectiveness models and value frameworks to aid in product coverage assessments. The Institute for Clinical and Economic Review (ICER) is one such organization with its Quality-Adjusted Life Year (QALY)-based cost-effectiveness framework to determine drug value. It has accessed various rare-disease therapies, recommending that US payers do not cover them since their therapeutic value does not justify their pricing within the organization’s cost-effectiveness threshold.10
  • Evidence Requirements
    In the rare disease space, manufacturers often rely on surrogate endpoints as a means of FDA-approval. Payers, however, are placing increasing emphasis on real world evidence and long-term outcomes of orphan products outside of submitted surrogate clinical endpoints to determine long-term product value.

The payer perspective is the critical component of optimizing patient access for orphan products. As manufacturers look for ways to succeed in the rare disease space, they must ask: How can we reduce payer uncertainties around the cost versus value of rare disease therapies?

From the developer’s perspective, key considerations for success in rare diseases with payers include:

  • Value Communication
    A clear and scalable demonstration of value across all payer archetypes is essential, as rare diseases may not be the top-of-mind indication for payers. Proactive and early engagement on clinical outcomes and health economic modeling can prove beneficial. This effective messaging around value is a key driver of commercial pull-through strategies.
  • Evidence Generation Strategies
    Rare diseases may see large evidence gaps due to a limited patient size and lack of available information. For similar reasons, evidence generation may also be challenging.  Manufacturers must assess evidence gaps and be innovative in generating additional evidence that will convey long-term therapeutic value. Tapping into patient registries, generating data through patient support programs, or collaborating with health systems for electronic medical record (EMR) chart studies are just a few options for real world data analyses. Predictive modeling and simulation may allow for the translation of clinical trial data to real world outcomes data. Conveying evidence plans to payers may provide further insight into what types of data may be best.
  • Innovative Contracting
    Manufacturers should consider payers a partner and seek innovative ways to mitigate payer concerns over high price orphan products. Innovative methods for contracting can help decrease payer cost burden while optimizing patient access and care. From risk-sharing to annuity models, it is critical to assess key factors such as clinical outcomes, target population, and payer archetype. This can help determine the best contracting strategy to pursue and ultimately reduce access-related challenges.


  1. https://www.who.int/medicines/areas/priority_medicines/Ch6_19Rare.pdf
  2. https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases
  3. https://www.fda.gov/news-events/fda-voices-perspectives-fda-leadership-and-experts/fda-working-bridge-gaps-and-meet-needs-rare-disease-product-development
  4. https://www.evaluate.com/sites/default/files/media/download-files/EvaluatePharma_Orphan_Drug_Report_2019.pdf
  5. http://info.evaluategroup.com/rs/607-YGS-364/images/EPOD17.pdf
  6. https://www.ajmc.com/newsroom/orphan-drugs-have-lower-drug-development-costs-compared-with-nonorphan-drugs
  7. https://www.npr.org/sections/health-shots/2019/05/24/725404168/at-2-125-million-new-gene-therapy-is-the-most-expensive-drug-ever
  8. https://www.precisionmedicinegrp.com/pfv/article/rare-diseases-are-losing-their-immunity-in-formulary-exclusion-lists/
  9. https://www.pm360online.com/the-impact-of-express-scripts-2019-formulary-exclusion-list/
  10. https://www.healthaffairs.org/do/10.1377/hblog20181105.38350/full/

As rare disease innovation intensifies, developers are turning to experts in scientific value assessment, such as Certara’s Evidence & Access team, to bridge the gap between innovator’ and payer’ perspectives, between value and price, and between profit and sustainable patient access. To learn more about what works and what doesn’t in our rapidly changing reimbursement world, please watch this webinar.