CBER chief on remote work, CRISPR-Cas9, and rare disease gene therapy accelerated approval guidance

The use of CRISPR-Cas9 gene editing technology has potential to transform the field of gene therapy through its simple and cost-effective delivery mechanism, said Peter Marks, director of the US Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER), during a 23 April webinar sponsored by the Alliance for a Stronger FDA. He also addressed FDA’s forthcoming guidance on accelerated approval for gene therapies for treating rare diseases.

Marks also said that FDA needs to develop an agency-wide remote work policy. Currently, different centers within FDA have different policies in this area, he said. “We cannot have different centers in the agency have different human resource polices.” He added that “if we don’t have our medical product centers having similar policies this will lead to too much movement within the agency.”

Currently, FDA is in a “semi-stable state” allowing employees to either work remotely or on-site. He added that “my guess that the new normal will be a hybrid” model combining remote with onsite work.

CRISPR-Cas9

Marks said the advent of CRISPR-Cas9-edited gene therapy is “the most promising” new technology under his domain, when asked to address some of the more promising new areas for future development.

“The ability of CRISPR-Cas-9 to potentially help address human disease in a manner that has never been seen before is pretty remarkable.” He said that since the discovery of this gene editing technology discovery about 12 years ago, when it was “just bacteria in the immune system,” the field has undergone “multiple iterations and continues to evolve.” He added that with the help of artificial intelligence, the field is “getting even better.”

He further noted that these technologies can be “game changer” for rare diseases and involve a much simpler delivery process compared to gene therapies derived from adeno-associated viruses (AAV), which require the use of complex mammalian cell cultures.

Last December, FDA approved the first CRISPR-Cas9-edited cell therapy, Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel) for sickle cell disease.

These therapies can be “really transformative. It will not be tomorrow, but in probably five to years away, if we do our jobs right, it can be a very transformative situation. Obviously, we will have to do it right and make sure there are no adverse events but right now the future looks quite promising,” Marks said.

Accelerated approval buckets

Marks was asked to address CBER’s plan for issuing guidance addressing accelerated approval for gene therapy products for rare diseases, an area of great interest. Marks responded that he envisions “three different buckets” for guidance in this area.

“When thinking about gene therapy, it is a lot simpler in some ways than when you are dealing with small molecule products or protein-based therapies. In delivering a gene therapy I think of this in buckets. The first bucket is something you can measure that correlates with an aspect of health so just measuring that product you know the gene therapy will be effective.”

An example of this are treatments for hemophilia or beta-thalassemia; if patients make hemoglobin on their own when they normally cannot “that is a low hanging fruit” for guidance.

Another bucket is for gene therapy products that are a bit more complicated and cannot be easily measured, there are other elements such as upstream marker or a downstream marker that can be used to measure the treatment’s effects.

He said the third bucket is reserved for “more complex genetic diseases” where gauging the treatment’s effect may be more challenging. Marks said that a forthcoming guidance can foreseeably address all three buckets.

Budget

In addressing the agency’s budget, Marks said that if FDA does not get the additional funding to cover employee pay increases, the agency will have to cut funding in other areas, such as laboratory funding. FDA is asking for a nearly 5% increase its budget for FY 2025, to offset inflation. (RELATED: FDA officials say FY 2025 budget increase needed to offset inflationary pay increases, Regulatory Focus 16 April 2024)

Marks said that “with the pay increase, if that falls behind, our laboratory program falls behind, and many other things fall behind.”

CBER chief on remote work, CRISPR-Cas9, and rare disease gene therapy accelerated approval guidance

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