Convergence: FDA officials offer updates on START, STAR pilots

LONG BEACH, CA – US Food and Drug Administration (FDA) officials shared an update on the status and progress of two pilot programs that aim to promote the development of innovative medicines at RAPS Convergence 2024. One addresses the development of treatments for rare diseases, while the other is intended to speed the development of therapies that address an unmet medical need.

The two pilots are the Support for clinical Trials Advancing Rare disease Therapeutics (START) program and the Split Real Time Application Review (STAR); both of these programs were mandated by the seventh iteration of the Prescription Drug User Fee Act (PDUFA VII).

Wei Liang, a reviewer in FDA’s Office of Therapeutic Products within the Center for Biologics Evaluation and Research (CBER) said that FDA has selected seven companies to participate in the START pilot after it was announced last year. (RELATED: Convergence: CBER chief discusses priorities, touts gene therapy approvals, Regulatory Focus 5 October 2023)

The START pilot includes investigational products submitted to both CBER and the Center for Drug Evaluation and Research (CDER). The CBER pilot participants include Grace Science for its NGLY1 deficiency treatment; Myrtelle for its Canavan disease candidate; Neurogene for its Rett syndrome gene therapy; and Moderna its isolated methylmalonic acidemia treatment. The CDER participants include Larimar Therapeutics for its Friedreich's ataxia treatment, Calico Life Sciences for its vanishing white matter disease candidate; and Denali Therapeutics for tis treatment of Sanfilippo syndrome.

Liang noted that FDA has approved a handful of cell and gene therapies for rare diseases in recent years – four were approved in FY 2021, four in FY 2022, seven in FY 2023, and five in the first three quarters of FY 2024.

She noted that these are complex products that can take a long time to develop and move through the regulatory process. For example, CAR-T cell therapies can take anywhere from three to nine years from IND submission to BLA approval, and it can also take between five and ten years to review adeno-associated virus (AAV)-based gene therapies.

In an effort to accelerate the regulatory review phase, the START pilot aims to provide a “more rapid, ad hoc communication mechanism,” Liang said.

During an initial meeting, the sponsor requests meeting with FDA on specific issues on their applications and agree on the regulatory milestones for the development program. There are also subsequent communications through pre-scheduled standing meetings to identity emerging issues that crop up during the drug’s development.

STAR pilot

Cathryn Lee, of FDA’s Office of Program Operations (OPO) within the Office of New Drugs at CDER, explained some of the nuances of participating in the STAR pilot and discussed how the program differs from other programs for innovative drugs.

FDA’s STAR pilot aims to shorten the review time of supplements for existing drugs and biologics in cases where there is an unmet medical need. (RELATED: FDA offers details on PDUFA VII STAR review pilot, Regulatory Focus 4 October 2022)

Lee explained that the STAR pilot will apply to efficacy supplements across all therapeutic areas and review disciplines that meet specific criteria. Accepted STAR submissions will be submitted in a “split” fashion, specifically in two parts.

The first part of the application should contain all the elements of the supplemental application, except for the clinical study report (CSR), integrated summary of effectiveness (ISE), and integrated summary of safety (ISS).

The second part of the application can be submitted later and should contain the CSR, ISE, and ISS.

Lee explained that the program differs from other pilots such as the Real-Time Oncology Review (RTOR) pilot, as the STAR pilot is a PDUFA program open to development programs from any therapeutic area, while RTOR is not a PDUFA program and is only available for oncology drugs. It also differs from a rolling review (RR) because a RR is only available to drugs with a fast track or breakthrough therapy designation (BTD).

Lee said that FDA will conduct an interim assessment of the program by the end of FY 2025 and will host a public workshop on the program in FY 2026.

Convergence: FDA officials offer updates on START, STAR pilots

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