CBER’s Office of Therapeutic Products (OTP) and CDER’s Office of New Drugs have announced in a Federal Register notice the opportunity for a limited number of development programs to participate in the START pilot program, which aims to accelerate the pace of development of novel CBER- and CDER-regulated products that are intended to treat rare diseases. The pilot will augment the currently available formal meetings between FDA and sponsors, by providing sponsors selected for START with enhanced communications with FDA review staff, which will include, at a minimum, an initial meeting to review features of the pilot, to discuss a pathway intended to support a marketing application, and to discuss specific issues for which a sponsor requests enhanced communication with FDA. Additional communications will also include ongoing interactions via email or teleconference that take place on a scheduled and/or as needed basis as agreed upon by the sponsor and FDA.

Who is eligible for the START program?

In this first iteration of the program, FDA will accept requests to participate in the START Pilot Program and select up to three participants from each Center (CBER and CDER). To be considered for the START Pilot Program, participants must meet the following eligibility criteria:

1. For an application to CBER, there must be an OTP-regulated Investigational New Drug Application (IND) for a cellular or gene therapy product that is being developed for eventual marketing approval, that is intended to address an unmet medical need as a treatment for a rare disease or serious condition, which is likely to lead to significant disability or death within the first decade of life.

2. For an application to CDER, the product must be intended to treat rare neurodegenerative conditions (including those of rare genetic metabolic etiology).

3. An IND must have been submitted in or converted to Electronic Common Technical Document (eCTD) format, unless a waiver has been granted and remains in active status.

4. The sponsor must have demonstrated substantial effort to ensure that that Chemistry, Manufacturing, and Controls (CMC) development aligns with clinical development.

In addition, applicants must state whether there is a breakthrough therapy (BT) designation for the product; if it is a CBER-regulated product, the applicant must note whether there is a BT designation and/or regenerative medicine advanced therapy (RMAT) designation. In selecting the program participants, FDA said it intends to consider factors including:

• potential clinical benefits of the product,

• whether resolution of the specific issues noted by the sponsor in their request to participate in the pilot could be facilitated through enhanced communication to improve efficiency of program development,

• whether there is a BT or RMAT designation for the product (although it’s not clear whether these designations would be beneficial (or not) to an applicant), and

• whether the CMC development timeline aligns with clinical development plans.

While INDs for combination products may be eligible, “products that require significant cross-Center interactions may be less likely to be selected for the pilot.” FDA further notes that application readiness will be critical in its selection determination.

What should be submitted in a START program application?

The request should include the initial specific development issue(s) that will be the subject of enhanced communication, and a proposed communication plan between the sponsor and review staff. In addition, an applicant should provide the following:

1. Program development plan. The plan should describe the current state of program development, including any ongoing activities not already detailed in the IND.

2. Issue list. Any specific issues (grouped by review disciplines) for which the prospective applicant is seeking enhanced communications with FDA review staff to facilitate program development.

3. Timeline. The planned timeline for initiation of the clinical study or studies intended to provide the primary evidence of effectiveness to support a marketing application or for a pre-BLA/pre-NDA meeting request.

4. Communication plan. The proposed communication plan for interactions between FDA review staff and the sponsor, including the proposed timing and format (e.g., email or teleconference).

Other FDA efforts to promote rare disease drugs

In addition to the START pilot program, FDA is conducting other efforts to advance the development of new drugs to treat rare diseases. FDA has opened a docket for stakeholder feedback as part of the Learning and Education to Advance and Empower Rare Disease Drug Developers (LEADER 3D) program under the CDER Accelerating Rare disease Cures (ARC) program. FDA said it will use feedback from the program for the identification of knowledge gaps in rare disease drug development and the development of publicly available resources to inform stakeholders who design and conduct rare disease drug development programs on regulatory considerations surrounding clinical trial design. 

FDA also recently published a Request for Information for stakeholders to provide feedback regarding critical scientific challenges and opportunities to advance the development of cellular and gene therapies designed for an individual or very small number of patients diagnosed with a rare disease. FDA said it plans to use this information to inform the planning of possible future meetings, workshops, educational programs, and/or discussion papers that will facilitate the development of additional regulatory tools and/or frameworks.

If you may be interested in responding to FDA’s cell and gene therapy RFI or ARC docket, or in applying to the START pilot program, or if you have questions on planning clinical trials for rare diseases more generally, feel free to contact the Hogan Lovells with whom you generally work or one of the authors of this alert.