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FDA wants more details on Sarepta gene therapy, potentially delaying final test

The Food and Drug Administration has asked Sarepta for an additional laboratory test on its gene therapy for Duchenne muscular dystrophy before the biotech uses drug product made via a commercial process in a planned Phase 3 trial.Specifically, the FDA told Sarepta to use a new “potency assay,” a test for whether the gene therapy can reach get into cells and spur production of a key protein Duchenne patients lack. It’s unclear to what degree the request will delay a large study of the treatment that Sarepta had said would begin by the end of the year.The disclosure makes it more likely that Sarepta’s trial will start after a similar late-stage study from rival Pfizer. Both aim to show that gene therapy can change the trajectory of Duchenne, a crippling and deadly genetic disease with no cure. To prove that to regulators, both will need to demonstrate their commercial-grade product is effective in Phase 3 trials before seeking FDA approval.

One of the most competitive races in gene therapy is taking place in Duchenne muscular dystrophy, where multiple rival programs seek to prove a one-time treatment can at minimum slow, or perhaps even halt, the disease’s progression.

These treatments send genetic instructions into the body to produce a shortened form of the muscle-protecting protein dystrophin. The hope is that this tiny dystrophin acts like the real protein and gives patients more time with the ability to walk, avoid breathing support and function independently than they would have otherwise.

This hasn’t been proven; so far, snippets of data from early-stage trials showed the gene therapies can spur the body to make the shortened dystrophin, and suggested they might be helping patients.

Because of the deadly nature of Duchenne and a lack of effective treatments, multiple drugs have recently been approved before proof was obtained that they truly work. The path forward for gene therapies appears to be similar, with one key, additional requirement: Developers must show their product made from a commercial process is just as effective as what they use in early clinical trials.

At a virtual conference earlier this year in June, Sarepta CEO Doug Ingram said the company aims to file for approval of its treatment off of interim results from the Phase 3 study and more complete data from an ongoing, mid-stage test. The expectation was Sarepta would have all of that information by the first quarter of 2021.

The FDA needs to agree to that plan, however. The agency already surprised one gene therapy developer, BioMarin Pharmaceutical, this year when it rejected the biotech’s hemophilia treatment and asked for more data.

Nonetheless, the race is on between Sarepta and Pfizer to begin testing their commercial product in a Phase 3 trial. Though Sarepta has been ahead, its lead over Pfizer has narrowed.

Up until now, Sarepta has said its Phase 3 study could begin by the end of the year. In May, Pfizer said it would do so as well, potentially before Sarepta. That appears possible now, given the FDA needs more information from Sarepta before it can begin its trial.

It’s unclear how long Sarepta might have to wait. Spokesperson Tracy Sorrentino said the company has “several assays and data on hand that we believe will be acceptable,” and would get more clarity on the timing “once we can engage with FDA.”

Sarepta may need to validate a new assay and it also has to get to the FDA, which is more challenging than usual because of the coronavirus pandemic. Still, while Wall Street analysts speculated possible delays of weeks to months, several of them, after speaking with Sarepta executives, believe the company’s program will not be significantly affected.

Baird analyst Brian Skorney, for instance, described the FDA’s request as a “relatively minor issue.” Piper’s Tyler Van Buren noted Sarepta is hopeful the situation can be resolved in three to four months, which could keep the company on track to file for approval “relatively in-line with current expectations.”

Three years ago, AveXis, developer of the gene therapy Zolgensma, was delayed by several months in starting a trial due to a request from the FDA regarding potency assays, SVB Leerink’s Joseph Schwartz wrote in a client note.

“We are working to gather the data and get in front of the agency as quickly as possible,” Sarepta’s Sorrentino said.

If the program were delayed by a quarter or less, the Phase 3 trial would likely start by early next year, with interim results coming at either the end of the first quarter or early second, Van Buren wrote.

Pfizer’s planned study isn’t yet recruiting patients, according to the database.