Contributor: How Patients and Caregivers Can Be a Catalyst for Rare Disease Innovation

Philip Cyr, MPH

Many years ago, a very wise physician said at least half of all diagnoses come from the patient's medical history and physical examination. Clearly, what the patient tells you is vitally important, and nowhere is this truer than in the rare disease space.

In the United States, the Orphan Drug Act defines a rare disease as a condition that impacts fewer than 200,000 people. It is estimated there are approximately 7000 rare diseases affecting 30 million individuals in the United States and up to 250 million individuals worldwide.^2,3

When considered as a whole, all rare diseases affect a tremendous amount of individuals, and the unmet medical need for individuals living with these conditions has made this a very active area for research and development.⁴ For example, the Center for Drug Evaluation and Research reports that 51% of the drugs approved over the last 4 years were for rare diseases.⁵

As more rare disease therapies enter the clinic, patients, caregivers, and the advocacy community have a unique opportunity to be a catalyst for innovation.

What patients tell their physician can aid in their diagnosis, and can be seen and heard by pharmaceutical manufacturers, researchers, payers, and regulators which can optimize development and access to new therapies. Two of the most impactful ways to catalyze innovation in rare diseases are helping to define the disease and meaningful outcomes, and being a voice to regulators and payers.

Helping to Define the Disease for Stakeholders

With many rare diseases, there may be limited knowledge to guide researchers, regulators, and payer decisions regarding questions that are important to developing and evaluating a therapy. For example, what is the natural course of the condition? Are there more or less severe forms? How does the condition impact an individual’s functional status and health-related quality of life? What is the impact on family members/caregivers?

The answers to these questions are central to understanding where to focus research and clinical trial design. The questions will also be important further down the line as companies look to communicate value to regulators and payers to facilitate access to these potentially life-altering therapies.

Patients with rare disease and their caregivers are essential catalysts in getting the above answers by sharing their experiences and data. This can take many forms:

Natural History Studies

A good example of a rare disease where patients and caregivers are making an impact is the RECENSUS study, an international, multicenter, cross-sectional medical record review of males diagnosed with X-linked myotubular myopathy (XLMTM). Symptoms include severe hypotonia, weakness, respiratory distress, and early mortality, resulting in significant disease burden and healthcare utilization for impacted individuals.^{6, 7}

The study examined the standard of care, diagnostic pathway, and clinical outcomes for all individuals with XLMTM and within certain severity, such as ventilator status.⁷ This type of evidence is crucial to choosing appropriate clinical trial endpoints, sample size, and inclusion and exclusion criteria. It can also be used to inform health economic models that can be used to advocate with health insurance organizations and health technology appraisal organizations.

Family and Caregiver Survey

A survey was conducted to quantify parent and caregiver costs, including direct medical and non-medical, out-of-pocket expenses, health resource use, and quality of life due to the impact of XLMTM. This type of evidence can be impactful to payers, health technology assessments, and regulators when making decisions.⁸

Patient Registries

Many patient advocacy organizations have developed patient registries to help further understand the disease and all that surrounds it. Registries are powerful tools to connect affected patients, families, and clinicians; learn the natural history, evolution, risk, and outcomes; support research on genetic, molecular, and physiological basis; and establish a patient base for evaluating therapies.⁶

Historically, from a research perspective, one of the issues with patient registries has been that they have been siloed, often sequestered within the community of researchers with that specific disease. However, new tools and platforms like Rare-X are enabling researchers to query disparate datasets within and across rare disease, often speeding time to discovery, development, and approval.

Specifically, Rare-X contains diagnostic decision support with tested algorithms and data spanning 8000+ rare diseases; data collection platform capacity to build and host thousands of registries; and a federated data analysis platform that enables researchers to query dataset.⁹

Being a Voice to Regulators and Payers

When it comes to rare disease, patient advocacy can be impactful when determining access to therapy. A recent survey of US payers found that 71% of payers rate patient advocacy as a key consideration in their decision-making process.

When discussing treatments with payers, they will weigh efficacy/safety and cost-effectiveness higher than quality of life.^10,11 That said, putting a face to a disease can be a highly effective tactic for increasing the likelihood of optimal coverage.

Parting Thoughts

As Kyle Bryant, a patient with rare disease, and the wise physician pointed out, patients and caregivers hold one of the most important keys to the drug development process and overcoming barriers to access their own experience. Yes, it is highly personal, but by sharing them, they can truly be a catalyst for therapy innovation.

References

1. Kyle Bryant, “Meet Kyle Bryant”. YouTube. September 29, 2022. Accessed September 28, 2023. https://www.youtube.com/watch?v=82x1m-NWODM.

2. US Food and Drug Administration. Rare diseases: Natural history studies for drug development: Draft guidance for industry. 2019. Accessed December 28, 2022. https://www.fda.gov/media/122425/download.

3. Nguengang Wakap S, Lambert DM, Olry A, et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2020;28(2):165-173.

4. U.S. Food and Drug Administration. CDER continues to make rare diseases a priority with drug approvals and programming to speed therapeutic development. Accessed December 28, 2022. https://www.fda.gov/news-events/fda-voices/cder-continues-make-rare-diseases-priority-drug-approvals-and-programming-speed-therapeutic.

5. Larkindale J, Betourne A, Borens A, et al. Innovations in therapy development for rare diseases through the rare disease cures accelerator-data and analytics platform. Ther Innov Regul Sci. 2022;56(5):768-776.

6. Beggs AH, Byrne BJ, De Chastonay S, et al. A multicenter, retrospective medical record review of X-linked myotubular myopathy: The recensus study. Muscle Nerve. 2018;57(4):550-560. doi:10.1002/mus.26018

7. Miller B, Jensen IS, Dean R, et al. Health resource use in patients with x-linked myotubular myopathy (XLMTM): Data from the RECENSUS Study. ISPOR 25th Annual International Meeting. Orlando FL. 2020.

8. Miller B, Yao W, Dean R, et al. Understanding the impact of XLMTM on parents and caregivers in the US: an analysis of survey results. ISPOR 18th Annual European Meeting, Milan IT. 2020.

9. Rare-X Global Genes. Accessed September 28, 2023. https://rare-x.org/.

10. Gliklich RE, Dreyer NA, Leavy MB, editors. Registries for Evaluating Patient Outcomes: A User's Guide [Internet]. 3rd edition. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Apr. 20, Rare Disease Registries. https://www.ncbi.nlm.nih.gov/books/NBK208609/.

11. Narayanan S. Payer–patient engagement framework to strengthen ethical formulary decision-making in rare disease arena in the USA. Future Rare Disease. 2023;3(1). doi:10.2217/frd-2022-0016.