DALLAS, Texas—Since 2017, the US Food and Drug Administration (FDA) has approved 12 gene therapies—including 5 in 2022 alone—compared to none less than a decade ago. That’s an indication of how quickly the gene therapy pipeline has evolved, a top FDA official pointed out.

Peter Marks
Peter Marks, MD, PhD, director of the US Food and Drug Administration’s Center for Biologics Evaluation and Research gives the keynote address at the Muscular Dystrophy Association’s 2023 Clinical & Scientific Conference in Dallas, Texas. (Photo by Larry Luxner)

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER), made the remarks during his keynote address on “Realizing the Promise of Gene Therapy” at the Muscular Dystrophy Association’s 2023 Clinical & Scientific Conference here.

“We don’t have all the answers at FDA. We’re trying to get there and we’re going to make mistakes along the way,” he told nearly 1500 in-person participants and another 555 watching online. “But we understand that rare disorders are incredibly important in the area of gene therapy, because together, these diseases affect millions upon millions of people in the United States alone.”

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Cautioning of the possible need for repeated administration and the potential for unpredictable side effects, Dr. Marks warned that this is “not a curative therapy.” Yet, he said, “there’s a reasonably high probability of success if you’ve done your animal work [in clinical trials] correctly.”

The presentation by Dr. Marks comes as the FDA weighs final approval for SRP-9001, an investigative gene therapy developed by Sarepta Therapeutics to treat Duchenne muscular dystrophy—a rare disease that currently has no cure.

Industry observers say SRP-9001, if approved, will likely retail for $3 million or more. The FDA recently announced it would convene a meeting of independent experts to review Sarepta’s application; the company later said it was “disappointed,” but that SRP-9001 would still likely win final approval on May 29, 2023.

“There are disadvantages to gene therapy, for one the complexity and cost of manufacturing, which is not something to sneeze at,” Dr. Marks said without specifically elaborating on Sarepta’s application. “There might be irreversible side effects. You might not be able to give the gene therapy again because there’s immunity. There’s also a need for special expertise to administer these, and do it well. If not, bad outcomes are possible.”

In addition, he said, gene therapy presents the many challenges of a new business model.

“The pharma industry is used to ‘pay as you go.’ You get your prescription refilled every 30 days, but when you give someone a therapy once and they don’t need it again—if you’ve done your job well and your therapy is curative—then once you’ve taken care of the patients with that disease now, on a yearly basis your market will be smaller.”

Dr. Marks said the $2.1 million drug onasemnogene abeparvovec-xioi (Zolgensma®), marketed by Novartis for spinal muscular atrophy (SMA), is the gold standard when it comes to gene therapy.

“This has proven to be what gene therapy looks like when things go really well,” he said. “We still don’t know the long-term benefits, but this is very promising. It’s really transformative.”

He added: “We don’t get into the cost of therapies. Nonetheless, we are very much aware of the issue of product costs. That actually limits availability. We’re seeing public-private partnerships help enable access for very small populations. But a robust ecosystem will lead to production across a variety of different diseases.”

It’s also a matter of what’s already on the market for a specific rare disease, the CBER chief pointed out.

“In hemophilia, the bar for gene therapy is quite high because there are existing therapies,” he said. “On the other hand, if you have a genetic defect that’s killing children early on, maybe we’ll have to settle on a first-generation product and evolve later.”  

One of the biggest factors going forward, Dr. Marks said, is the sky-high cost of manufacturing, which must be brought down if gene therapy is to make a real difference on a large scale.

“Manufacturing is no longer in its infancy, but in its toddler stage. We need to get it to maturity as quickly as possible, because it will make a big difference in making these therapies available.”

To spur that along, in February 2023, the CBER reorganized its Office of Tissues and Advanced Therapies into the Office of Therapeutic Products (OTP) and is currently looking to hire 150 reviewers and other specialists to handle the thousands of applications now flooding its website.

In addition, Dr. Marks said, “we hope to further accelerate the pace of development of therapeutics for very small populations with high medical need.”

“We think that by reducing this time at warp speed for promising therapies where we have constant communication, we may be able to make a difference. Even if we can only reduce the time by 25%, that translates into reduced suffering.”