Opportunities for Rare Disease Drug Manufacturers

  • This page as PDF


Rare disease drug manufacturers can advance clinical development through FDA programs aimed at facilitating pipeline innovation.

Drug approvals by the Food and Drug Administration (FDA) have increased in the past decade. Of the approximately 30 million people in the US living with a rare disease, however, most do not have FDA-approved treatments. Manufacturers with clinical programs for rare and ultra-rare diseases face multiple challenges in development, especially in diseases with heterogeneous presentations. Manufacturers and the FDA have noted in particular that the resource investment required to test, validate, and implement endpoint assessment tools for these diseases can be a barrier to efficient and effective drug development.

Additionally, policy changes such as the Inflation Reduction Act (IRA) may create new market pressures for product lifecycles and certain therapeutic areas, driving companies to revise their R&D pipeline decisions. Some stakeholders expect these pressures to impede overall R&D pipeline innovation, with particular impacts on rare and ultra-rare disease drug development.

To support continued investment in rare disease treatments, the FDA, advocates, industry, and lawmakers have identified novel approaches that aim to enhance the success rate of rare disease clinical development programs.

Rare Disease Endpoint Advancement Program

The FDA launched the Rare Disease Endpoint Advancement (RDEA) Pilot Program at the beginning of 2023 to support novel endpoint efficacy development for drugs that treat rare diseases. The FDA will select up to three manufacturers per year between 2023 and 2027 to participate in the program. Manufacturers must submit a proposal with the type of data they intend to collect, the novelty of the endpoint, and its ability to establish evidence of effectiveness. Sponsors benefit from up to four focused meetings with the FDA to discuss endpoint development, in addition to regular investigational new drug-related milestone meetings.

The agency held an RDEA workshop in June 2023 to discuss novel endpoints in rare disease drug development. The workshop offered a glimpse into successful cases for endpoint collaboration between the FDA and the industry, highlighted challenges to endpoint selection and validation for rare diseases, and provided examples of innovative ways to determine clinically meaningful effects. Several types of endpoints were discussed, including surrogate endpoints, clinical outcome assessments, and multicomponent endpoints, along with an overview of the strategic rationale for leveraging one type over another (Table 1).

Table 1. Types of Novel Efficacy Endpoints Discussed for Rare Disease Development
Endpoint Type Brief Description When to Use Existing Challenges
Surrogate Endpoint Selected as it is “reasonably likely to predict clinical benefit” When full clinical endpoint is not available or appropriate; only available for assets pursuing the accelerated approval pathway Inconsistency in data standardization creates barriers for quick development; interpreting what is “reasonably likely” remains case-by-case at the FDA
Clinical Outcome Assessment Assessed to reflect how a patient feels, functions, performs, or survives from the perspective of a clinician, patient, non-clinician observer For conditions with heterogeneous clinical presentation across patients Limited disease natural history knowledge makes it difficult to accurately observe treatment effects
Multi-Component Endpoint Combines several clinical outcome measures that reflect multiple effects within a patient to culminate in a composite scoring When clinically meaningful improvement requires patients to improve on multiple disease outcomes Endpoints must be synergistic or cumulative to allow for appropriate weighting and observations

Other FDA Activity to Promote Rare Disease Treatments

In the past 5 years, the FDA has released three draft guidance documents focused on common issues in rare disease drug development. In September 2023, FDA announced availability of the Support for Clinical Trials Advancing Rare Disease Therapeutics pilot program, focused on offering an even greater level of communication between the FDA and the sponsor on related issues including study design, patient populations, controls, and endpoint selection.

Looking forward, the FDA is required to hold two more public RDEA workshops prior to September 30, 2026, and to provide a final report of its findings. Additionally, the FDA must issue draft guidance on best practices for development of efficacy endpoints by September 2026.

While these activities indicate the agency’s prioritization of rare disease drug development, areas of uncertainty remain regarding future clinical development and product approvals in this space.

Dive Deeper

Avalere applies our expertise in FDA regulatory strategy and evidence generation planning, access strategies for rare disease treatments, and strategizing impacts of IRA implementation to help healthcare stakeholders meet their strategic business objectives for approval and lifecycle management. To learn more about how Avalere can help you with clinical development planning, value, and access strategies for rare and ultra-rare disease assets, connect with us.

Webinar | A Closer Look at Patient Support On June 6 at 2 PM ET, Avalere experts will explore how potential implications of the Inflation Reduction Act (IRA)’s out-of-pocket cap, in addition to other key regulatory and policy activities shaping benefit design and patient cost-share (e.g., EHB), could impact patient commercial and foundation assistance. Learn More
From beginning to end, our team synergy
produces measurable results. Let's work together.

Sign up to receive more insights about Regulatory Strategy and FDA Policy
Please enter your email address to be notified when new Regulatory Strategy and FDA Policy insights are published.

Back To Top