2023: A Landmark Year for Cell and Gene Therapy Approvals

Robert M Califf, MD, MACC

2023 saw several major FDA approvals in the realm of cell therapy and gene therapy: exagamglogene autotemcel and lovotibeglogene autotemcel for sickle cell disease, beremagenegeperpavec for dystrophic epidermolysis bullosa, Lantidra for type 1 diabetes, delandistrogene moxeparvovec for Duchenne muscular dystrophy, and valoctocogene roxaparvovec for severe hemophilia A.^1-6 Outside of approvals, there was also significant progress made across the pipeline in therapeutic areas as wide-ranging as cardiology, endocrinology, dermatology, lysosomal disorders, oncology, hematology, neurology, ophthalmology, and autoimmune diseases. The field is expected to continue to grow from here.

In December 2023, CGTLive™’s sister publication, HCPLive™, sat down with Robert M Califf, MD, MACC, the commissioner of food and drugs at the FDA, to get his view on the major events of the year. One question was focused on the relatively high number of cell therapies and gene therapies that received FDA approvals in 2023 compared to previous years, and what this could mean for the future. Califf spoke about how far the field has come versus several decades ago when some people questioned the value of initiatives like the Human Genome Project.

HCPLive: This year has seen a number of landmark approvals of gene therapies and cell therapies. Can you speak to the importance of this?

Robert M Califf, MD, MACC: If you love biological science, or you're concerned about the well-being of people that currently have untreatable diseases or diseases for which the [current] treatments are not great, this is as exciting as it can get. I still remember when Francis Collins [MD, PhD, the former director of the National Human Genome Research Institute], commandeered the Human Genome Project at the National Institutes of Health decades ago, there were decades where a lot of people questioned: “What's the value of this stuff? Nothing's happening, it's just a science exercise.”

But now, we can go in and clip out a gene and put in a gene that remediates a disease. That's really the basis for using 2 different methods by 2 different companies for treatment of sickle cell disease, which has been in desperate need of better treatments for people who are often very disadvantaged in terms of access to the best health care. This is just the beginning, we're gonna see a huge number of cell and gene therapies. But we also have a lot to learn, for example if you ask about what are the off-target effects of inserting a gene or deleting a gene? We feel good enough now that these things should go on the market, but we're going to have a lot to learn in the postmarket phase and we’ll get better and better at it.

There’s also the cost issue, which is not the lane of the FDA—we're prohibited by law from considering costs—but if we want these treatments to be available for rural people, and people who have trouble having jobs because of their diseases, we're gonna have to figure out how to make it affordable and accessible. We're doing a lot of work with the Centers for Medicare & Medicaid Services (CMS). We don't tell CMS what to do and they don't tell us what to do at the FDA, but I think of it as a baton handoff. We run a lap in the premarket phase to make sure the treatment is safe and effective, at least for a group of people for a given condition. Then CMS has got to figure out: “How do we implement this? Who should be treated and who should be excluded?” All sorts of additional questions. So there’s a lot to work on there, but it’s really, really exciting. Who would have thought that we'd be at this phase now?

This transcript has been edited for clarity.

REFERENCES
1. FDA approves first gene therapies to treat patients with sickle cell disease. News release. FDA. December 7, 2023. Accessed January 26, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
2. FDA approves first gene therapies to treat patients with sickle cell disease. News release. FDA. December 8, 2023. Accessed January 26, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
3. Krystal Biotech receives FDA approval for the first-ever redosable gene therapy, VYJUVEK™ (beremagene geperpavec-svdt) for the treatment of dystrophic epidermolysis bullosa. News release. Krystal Biotech. May 19, 2023. Accessed January 26, 2023. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-receives-fda-approval-first-ever-redosable-gene
4. FDA approves first cellular therapy to treat patients with type 1 diabetes. News release. FDA. June 28, 2023. Accessed January 26, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-type-1-diabetes
5. Sarepta Therapeutics Announces FDA Approval of ELEVIDYS, the First Gene Therapy to Treat Duchenne Muscular Dystrophy. News release. Sarepta Therapeutics. June 22, 2023. Accessed January 26, 2023. https://www.cgtlive.com/view/fda-approves-sarepta-s-landmark-dmd-gene-therapy-elevidys
6. U.S. Food and Drug Administration approves BioMarin's ROCTAVIAN™ (valoctocogene roxaparvovec-rvox), the first and only gene therapy for adults with severe hemophilia A. News release. BioMarin Pharmaceutical Inc. June 29, 2023. Accessed January 26, 2023. https://investors.biomarin.com/2023-06-29-U-S-Food-and-Drug-Administration-Approves-BioMarins-ROCTAVIAN-TM-valoctocogene-roxaparvovec-rvox-,-the-First-and-Only-Gene-Therapy-for-Adults-with-Severe-Hemophilia-A