By: Jill Hartzler Warner, J.D.
The U.S. Congress and the Food and Drug Administration have long focused on bringing new therapies to patients with rare diseases, including children.
Two years ago this week, Congress made another contribution to this effort by enacting the Food and Drug Administration Safety and Innovation Act (FDASIA). The law directs our agency to take two actions to further the development of new therapies for children affected by rare diseases: (1) to hold a meeting with stakeholders and discuss ways to encourage and accelerate the development of new therapies for pediatric rare diseases, and (2) issue a report that includes a strategic plan for achieving this goal.
There are unique challenges when developing drugs, biological products and medical devices for the pediatric population. Not only is there the potential for children to respond differently to products as they grow but there are also additional ethical concerns for this patient population.
But these challenges are further compounded when developing therapies for pediatric rare diseases. For example, rare disease product development, by definition, means there is only a small potential group of patients available to participate in clinical studies that can help determine whether a product is safe and effective.
In our FDASIA meeting in January, we heard a variety of suggestions on clinical trial design and data collection from hundreds of the participating stakeholders from academia; clinical and treating communities; patient and advocacy groups; industry and governmental agencies.
These discussions helped inform our Strategic Plan for Accelerating the Development of Therapies for Pediatric Rare Diseases, which we posted on our website today. It outlines how we plan to meet the following four objectives:
Enhance foundational and translational science. Our strategy is to fill essential information gaps through such measures as fostering the conduct of natural history studies for pediatric rare diseases and by identifying unmet pediatric needs in medical device development. We also plan to issue guidance for sponsors on common issues in rare disease drug development and to refine and expand the use of computational modeling for medical devices.
Strengthen communication, collaboration, and partnering. Robust cooperation within FDA, among agencies, governments and private entities is necessary to enable the exchange of information on the issues of developing treatments for pediatric rare diseases. Single entities by themselves usually don’t have sufficient resources or expertise to overcome the product development challenges posed by pediatric rare diseases.
Advance the use of regulatory science to aid clinical trial design and performance. Regulatory science helps develop new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all FDA-regulated products. Of note, we plan to facilitate better understanding of biomarkers and clinical outcome assessments that are useful for the development of treatments for pediatric rare diseases. We also plan to further develop the expedited approval pathway for medical devices intended to treat unmet medical needs; and use FDA’s web-based resources to update and expand awareness of issues involving the development of medical products for pediatric rare diseases.
Enhance FDA’s review process. Our strategies include fostering efforts to learn patients’ and caregivers’ perspectives and incorporating this information into medical product development. We also plan to further develop and implement a structured approach to benefit-risk assessment in the drug review process and establish a patient engagement panel as part of the medical device advisory committee process.
The report notes our use of expedited programs to speed rare disease medical product development. But it’s important to note that our own regulatory flexibility is reducing the number of approvals under one of these procedures: the accelerated approval program for drugs that treat serious conditions and that fill an unmet medical need based on a surrogate or intermediate endpoint (that is, a measure such as blood test or urine marker that is believed to be indicative of a disease state and treatment effect, but not demonstrative of a direct health gain to the patient).
Most of the recent new drug approvals for rare diseases that would otherwise qualify for accelerated approval were given regular or “traditional” approval instead. As a result, they weren’t required to do confirmatory trials to verify clinical benefit, as required under accelerated approval, because we decided that the evidence was already strong enough.
The strategies outlined in this plan will help us achieve a major goal of FDASIA and for our agency, which is to speed the development of therapies for children with rare diseases.
Jill Hartzler Warner, J.D., is FDA’s Associate Commissioner for Special Medical Programs