The development of new therapies to treat orphan diseases is particularly perilous, due to limited patient populations, high costs, and difficulty in measuring clinical effectiveness. FDA officials are addressing these issues through the Rare Disease Cures Accelerator (RDCA) initiative in the Center for Drug Evaluation and Research (CDER). The goal is to shift away from a system of fragmentary research methods plagued by poor quality evidence to a more coordinated research approach and methods that can expedite development of drugs to treat some of the 7,000 rare diseases affecting 25,000-30,000 people. 

Main strategies involve establishing common platforms and standardized tools and infrastructure to improve the quality of clinical trial data, explained Theresa Mullin, CDER acting director for strategic initiatives, at the “rare summit” sponsored by the National Organization for Rare Disorders (NORD) in Washington, D.C. last week. Mullin described how a more cooperative and collaborative approach can improve the quality of study endpoints, promote trial designs that accelerate learning, reduce mis-steps that cause failures and delays, and generate evidence needed for regulatory approval.

The RDCA provides the infrastructure for a cooperative approach to designing and conducting clinical trials in rare diseases to improve testing, protocols, and patient enrollment in clinical trials, Mullin noted. FDA is collaborating with the Critical Path Institute, NORD, patient groups, industry and other stakeholders on a framework for conducting more standardized rare disease natural history studies to help target treatment and design appropriate clinical trials. This involves examining the underlying causes of a disease, how it changes over time, variables in symptoms and experiences, and how the disease differs across patient populations. Patient perspectives remain key to providing insight into the most important impacts and what constitutes “meaningful change” in symptoms. 

Similarly, the RDCA Data Analytics Platform (DAP) aims to house integrated patient-level data from diverse sources, including clinical trials, observational studies, patient registries and real-world data from electronic health records, noted FDA acting commissioner Ned Sharpless at the NORD conference. A goal of the initiative, he pointed out, is to facilitate sharing of existing patient-level data to inform disease characterization and clinical trial design to accelerate development of new rare disease therapies. 

Another key RDCA component involves devising core sets of clinical outcomes assessments (COAs) to measure treatment impacts that matter most to patients and ideally are applicable to more than one rare disease. A new CDER grant program supports the development of core COAs and related endpoints, including those impacts that matter most to patients and are likely to demonstrate change. 

A more long-term RDCA goal is to establish a global clinical trials network able to facilitate the launch and conduct of studies involving rare diseases, Mullins added. Investigators and sites in the network would provide more uniformity and expertise in planning and conducting studies for rare disease therapies and ensure the collection of high quality data.

Broader investment

The RDCA initiative is supported by some of the $10 million in last year’s FDA budget provided by Congress to support innovation in advancing treatments for rare diseases. FDA’s Office of Orphan Products Development (OOPD) recently awarded two grants for natural history studies at academic research centers, one measuring acute pain in infants and young children, and the other assessing physical function across a range of chronic conditions. And 12 new grants to fund clinical trials involving rare disease therapies, building on FDA’s long-standing program to support researchers conducting clinical trials in this area, particularly to advance treatments for pediatric rare diseases. 

On a broader level, RDCA initiatives aim to advance common approaches and more sharing of research goals and methods to build on commonalties for developing new orphan drug therapies, Sharpless observed. He noted that FDA will continue to provide expedited review pathways for promising rare disease treatments and will issue more guidance documents to spur development of new pediatric medicines and gene therapies for rare diseases. And researchers receiving orphan products grants from FDA will contribute to discussions of common considerations for successful completion of rare disease studies.