Marks discusses CAR-Ts, CRISPR and START at regenerative medicine meeting

The benefits of CAR-T therapies, which have been used to treat 27,000 patients, outweigh the risks that these therapies pose to patients, Peter Marks, director of US Food and Drug Administration (FDA) Center for Biologics Evaluations and Research (CBER), said on 8 January at a meeting held by the Alliance for Regenerative Medicines.

“Make no mistake, the overall risk benefit profile [of these therapies] is still incredibly beneficial,” Marks said. He discussed some of the opportunities and some of the agency’s methods for promoting the development of cell and gene therapies

Marks noted safety concerns that were raised regarding cell therapies, leading FDA to investigate these products last November. The investigation was prompted by 20 reports of serious adverse events associated with these therapies, including hospitalizations and deaths, since the approval of the first CAR-T therapy in 2017 (RELATED: FDA investigates risk of secondary malignancies with CAR-T-cell therapy, Regulatory Focus, 30 November 2023).

At that time, the agency noted that was “evaluating the need for regulatory action” and that patient treated with CAR-T products should be monitored for life for any new malignancies, according to FDA.

At the Alliance meeting, Marks said CBER is also looking to promote the development of cell and gene therapies by encouraging the use of platform technologies. These technologies received a boost through the omnibus spending bill approved by Congress in December 2022, which directed FDA to establish a platform designation for drugs or biological products that have technologies that can be incorporated in or used by more than one drug or biological product (RELATED: Omnibus brings new advanced manufacturing programs to FDA, Regulatory Focus 11 January 2023). Marks added that FDA will issue be issuing guidance on the platform technology program in the future.

He further noted that the development of CRISPR technologies “is a poster child for a platform technology.” He said the early CRIPSPR technologies were “simple editing” and that now involve “much more complex editors.” He said that the same CRISPR technology can now be used to treat different diseases.

Using animal models for accelerated approval

Marks said CBER is also looking to accelerate the development of gene therapies though using animal models to support approval. Marks said that biomarkers from animal models can be used to connect biomarkers from human studies, with gene therapy clinical outcomes. “The key is to demonstrate that equivalent protein levels can be achieved in humans affected by the disease,” he said.

Three products have been chosen to participate in the Support for clinical Trials Advancing Rare disease Therapeutics (START) pilot, Marks said. The goal of the pilot is to accelerate the pace of development intended to address unmet medical needs for rare diseases or likely to lead to significant disability or death.

CBER launched the START Pilot Program in September 2023; the program enables sponsors to get advice and request ad hoc communications from reviewers on product-specific development issues, including clinical study design, choice of control group and clinical trial patient selection (RELATED: Convergence: CBER chief discusses priorities, touts gene therapy approvals, Regulatory Focus 5 October 2023).

[Editor's note: This article was updated on 9 January to correct a quote.]

Marks discusses CAR-Ts, CRISPR and START at regenerative medicine meeting

Related topics

Recommended content

Welcome to the new RAPS Digital Experience