Rich Moscicki, M.D., Deputy Center Director for Science Operations, FDA spoke to an audience of 75 senior physician executives from the Boston CMO Network on April 7, 2014. The event was hosted by Sarepta Therapeutics at the company’s new headquarters in Cambridge, MA.
Dr. Moscicki focused his prepared remarks on current CDER priorities, with particular emphasis on:
Rare Diseases continue to be a major focus for FDA. More than one-third of novel drugs approved in 2013 were for rare diseases. This continues a trend in recent years. From 2008-2013, one-third of NMEs and original biologics product approvals have been for rare diseases. This trend is expected to increase.
A therapy is considered a targeted therapy if the inclusion/exclusion criteria in pivotal trials or the label indications are based on a genetic test, biomarker or susceptibility test. An increasing percentage of new approvals are for targeted therapies, particularly with rare diseases. In 2013, 80% of rare disease approvals were for targeted therapies.
The growth in targeted therapies is creating orphan subsets within more common diseases, such as BRAF V600 mutation subsets of melanoma. Drugs developed for these smaller subsets of populations will have smaller clinical development programs and are expected to have improved risk-benefit profiles. They create a need for flexibility, novel trial designs, translational science development.
Dr. Moscicki noted that every FDA reviewer goes through rare disease training and senior leadership meets frequently to share views. The Rare Disease Program in CDER is a small group that provides education, training, input and advice to divisions and reviewers. This group tends to be more involved with smaller companies, helping them do the right thing.
Paths for Expedited Review
FDA has a number of paths for expedited programs including priority review, Fast Track, Breakthrough designation and Accelerated Approval. Rare Disease drugs are the majority in each category. Of the 14 Accelerated Approvals in 2013, 13 were for rare diseases.
Breakthrough Therapy is a new designation, established by FDASIA for expediting development and review for serious and life threatening diseases. Breakthrough Therapies receive more attention, with senior leadership updated and involved on a regular basis.
The industry has responded enthusiastically to this new program:
Dr. Moscicki outlined some of the lessons that have been learned to date:
When breakthrough therapy designation is denied, the most common reasons have been:
FDA has been devoting a lot of effort to improving drug shortages. Dr. Moscicki noted that 66% of drug shortages were due to quality issues. FDA’s plan has focused extensively on early notification as the key to resolving drug shortages. The agency is conducting risk-based analyses to determine ways of addressing shortages, including:
These measures are beginning to prevent and reduce the number of shortages. However, the industry needs to devote more effort and focus to improving manufacturing quality. There is a proposal to initiate a new Office of Pharmaceutical Quality with the following principles:
Patient-Focused Drug Development
Patient-focused drug development is part of FDA commitments under PDUFA V. The agency is particularly interested in hearing from patients to help understand severity of condition, degree of unmet need and risk tolerance.
The agency is convening at least 20 meetings on specific disease areas to gain patient perspectives. The 2013 meetings included narcolepsy and muscular dystrophy.
The agencies focus for meetings in FY 2014-2015 will be:
Summary Q&A Session
Dr. Moscicki summarized his prepared remarks noting that CDER initiatives in drug shortages, pharmaceutical quality, expedited reviews, pediatric rare disease vouchers, and patient informed decision making should have a significant impact on rare disease drug development. Rare Diseases have always been a leader in innovation and will continue to do so.
During a lively Q&A session, Dr. Moscicki touched on some additional topics:
The Boston CMO Network includes senior physician executives in the greater Boston area who are active in the biotech and pharmaceutical industry. The Network sponsors events for Boston-area physician executives to meet, interact and learn from each other.