Rare disease drug development is a challenging endeavor, but a worthy one. And despite the hurdles, there are numerous promising therapies underway to address the more than 10,000 rare diseases impacting over 400 million people globally. As these therapies make their way to market, the question remains:
Are the current pathways sufficient for supporting manufacturers with development and approval?
As recently as late January, FDA commissioner Robert Califf noted that “we’re about to see a tsunami of therapies for rare and ultra rare disease, and I don’t think any of us think the current pathways are optimal.” So it is no surprise that the FDA is attempting to provide new forums to support manufacturers through multiple avenues.
“We’re about to see a tsunami of therapies for a rare and ultra rare disease, and I don’t think any of us think the current pathways are optimal.” – Robert Califf M.D., Commissioner, FDA
Three efforts that have recently received attention include the following:
- The start of the Rare Disease Endpoint Advancement (RDEA) Pilot Program
- The announcement of the new Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program
- The finalization of noteworthy rare disease industry guidance
Rare Disease Endpoint Advancement (RDEA) Pilot Program
Announced in October 2022and kicking off in 2024, the FDA’s Rare Disease Endpoint Advancement (RDEA) Pilot Program aims to support the development of novel efficacy endpoints for drugs treating rare diseases. The program encourages collaboration between sponsors and the FDA throughout the endpoint development process. The hope is that innovation will be fostered and knowledge will be shared through presentations, guidance documents, workshops, and a public-facing website.
Preference is given to proposals with broader impacts on drug development, diverse endpoint types, and innovative approaches for surrogate endpoints, but novel endpoints are a must. It is important to note that the advice provided during the RDEA Program doesn’t equate to an approval, but the hope is that the additional guidance will enhance a manufacturer’s chances.
The initiative allows sponsors to submit RDEA proposals, with a maximum of three per year accepted from 2024 to 2027. Eligibility criteria include having either an active pre-Investigational New Drug Application (IND) or IND for a rare disease, though exceptions are made for sponsors initiating natural history studies.
“RDEA is a step in the right direction bring the FDA into the fold earlier and providing the guidance and confidence the clinical trial investigators need.” – James Long, PharmD, Director of Clinical Services, DKP
Rare Diseases: Considerations for the Development of Drugs and Biologics Products
Late last year, the FDA announced finalization of industry guidance on rare disease in Rare Diseases: Considerations for the Development of Drugs and Biologics Products. This document intends to assist sponsors of rare disease drugs and biologics with optimizing their drug development programs. The guidance touches on several challenges in drug development like clinical investigation design, use of biomarkers, and evidence of effectiveness and efficacy endpoints.
Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program
The FDA Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program is an initiative designed to accelerate the development and regulatory review of therapies for rare diseases.
The initiative addresses the unique challenges of drug development in rare diseases, such as limited understanding of the disease, small patient populations, and a lack of existing studies. The START Program was established in response to the critical need for more effective treatments for rare diseases, aligning with the Orphan Drug Act of 1983. The Act was a pivotal moment in rare disease drug development, providing incentives to stimulate the development of treatments for conditions affecting small populations.
Through START, the FDA aims to bridge the gap between the demand for effective rare disease treatments and the development challenges, enhancing the efficiency of clinical trials and ultimately improving patient outcomes in this underserved area. The program will enhance support to pharmaceutical companies and researchers by providing methodologies appropriate for rare disease research as well as guidance on clinical trial design, and regulatory challenges. .
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DKP’s Director of Clinical Services, James Long PharmD commented that “95% of rare diseases do not have a single treatment. Market exclusivity designations and the controversial accelerated approval cannot be the only safe haven for significant risks taken by novel science to address the needs of patients with rare disease.”
Clearly the FDA is aiming to help bridge the gap for rare disease patients and to prepare for the large number of treatments in development. As of 2022, over 50% (20 of 37) of novel drug approvals were for patients with rare diseases, which has continued to grow annually but still represents a small number of rare diseases and patients impacted. RDEA, START, and the rare disease industry guidance are just a few of the encouraging endeavors underway with the same common goal of bolstering the rare disease pipeline and likelihood of future successful approvals. The sooner these therapies can make it to market with as few hiccups as possible, the better the outcomes for the millions of impacted patients around the world.