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The agency is moving to smooth the pathways for orphan drugs, genetic therapies, and other scientific advances to yield more transformative medicines.
The main challenge in developing treatments for rare conditions is to identify, enroll, and retain sufficient numbers of patients in clinical trials to obtain meaningful information on product safety and efficacy. Since 1983, FDA has approved more than 450 orphan drugs, and new gene therapies and other scientific advances promise to yield more transformative medicines. FDA reports that some 40 companies are developing CAR-T technologies for multiple indications and that it is monitoring more than 600 active investigational new drug
applications (INDs) related to gene and cellular therapies. Yet, difficulties in devising and carrying out studies on small patient populations require new approaches to clinical research and product regulation.
FDA has moved to smooth the pathway for these important products, as seen in its orphan drug modernization plan. Issued last June, it aims to facilitate timely review of a soaring number of orphan drug designation requests, reported FDA Commissioner Scott Gottlieb at the annual meeting of the National Organization for Rare Disorders (NORD) in October. FDA officials described strategies for more efficient product testing, such as cross-over and randomized withdrawal studies suited to very small studies, and emphasized the importance of sponsors seeking early discussion of outcomes measures and target product profiles. And collaborative research platforms that share resources and data can help speed the path of effective treatments to patients, noted Petra Kaufmann of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH).
Gottlieb and others also emphasized the importance of developing natural history studies on how critical diseases arise and progress to help identify symptoms to treat and patients to test to obtain meaningful data on important endpoints. FDA recently awarded its first research grants to fund natural history studies, and NCATS is supporting research projects in this area. FDA’s orphan products grants program funded the new grants, along with 15 awards supporting early phase studies on rare diseases.
Additional assistance and accelerated reviews are available for important cellular and gene therapies under FDA’s new program for developing regenerative medicine advanced therapies (RMATs), which is overseen by the Office of Tissues and Advanced Therapies in the Center for Biologics Evaluation and Research (CBER). FDA recently unveiled a regenerative medicine regulatory framework, as specified by the 21st Century Cures Act.
FDA and sponsors acknowledge the increasingly important role of patient advocates in encouraging trial enrollment and design of studies that consider critical symptoms and hard-to-manage side effects. FDA has held dozens of patient-focused drug development meetings over the past five years to gain the views of patients and families on treating certain conditions and now is encouraging independent patient groups to organize their own R&D programs.
This approach is being formalized for medical devices, as seen at the first meeting of FDA’s Patient Engagement Advisory Committee (PEAC), which discussed effective methods for recruiting diverse patient populations and how requirements for informed consent, randomization, and study duration affect trial enrollment and retention. Established by the Center for Devices and Radiological Health (CDRH), the PEAC seeks to bring patient perspectives into the process of designing trials that incorporate real-world evidence and patient-reported outcomes. Patient representatives on the panel advised sponsors on outreach strategies for recruitment and on how reimbursement, transportation, and other support can reduce the burden of participation in trials.
Mobile health technologies may further encourage patient participation and retention in clinical trials. Wearables that measure temperature or detect falls can facilitate studies run at home, and monitors for blood pressure and levels of cholesterol or vitamin deficiencies in the blood may lower the bar for patient enrollment. Commissioner Gottlieb unveiled an R&D plan last June to encourage new mobile devices and software development, and last month FDA approved the first digital pill, a version of antipsychotic drug Abilify that contains a tiny chip able to send a signal to an adhesive patch that informs a smart phone when the pill is ingested.