Dive Brief:

• PepGen is in a holding pattern on its request to include U.S. patients in a Phase 2 trial of a muscle disorder treatment after the Food and Drug Administration put a partial halt on the study.
• The agency did not raise any questions about the company’s data in patients with the condition known as myotonic dystrophy type 1, or DM1, instead focusing on previously submitted preclinical work, PepGen said Wednesday. Specifically, the FDA seems concerned about drops in blood pressure in a study of mice that have not been seen in humans, analysts wrote.
• PepGen said it’s working with the FDA to address the concerns as quickly as possible. The company is continuing its Phase 2 work elsewhere and recently got permission to open the “Freedom2” study to patients in New Zealand, Australia and South Korea. PepGen shares fell almost 20% Thursday.

Dive Insight:

The timing of the FDA’s action is confusing because the agency has had the mouse data since mid-2024, Stifel analyst Paul Matteis wrote in a note to clients. It’s likely that PepGen’s bid to open U.S. sites for Freedom2 caused reviewers to re-examine the old data and issue the “surprise” hold, he added.

While any setback at the FDA can mean trouble, this one is probably manageable, Matteis speculated. Because PepGen executives “can make the case this was a mouse-specific finding, and they can share actual clinical data with the FDA, it would seem likely that this hold is resolvable,” he wrote.

PepGen is part of a wave of companies trying new techniques to better deliver RNA medicines and move beyond traditional targets in the liver. The company’s “PGN-EDODM1” medicine is an oligonucleotide-based therapy designed to address the genetic defect that causes DM1, an often life-shortening inherited disease that can cause a variety of mental and physical disabilities.

The FDA has a history of treading carefully with RNA medicines targeted at neuromuscular conditions. PepGen faced an agency hold back in 2023 before beginning Phase 1 testing of its DM1 treatment, following similar pauses for Sarepta Therapeutics, Dyne Therapeutics, Entrada Therapeutics and Avidity Biosciences. The FDA also slow-walked an experimental treatment for Duchenne muscular dystrophy that PepGen later discontinued for lack of efficacy.

Drugmakers have shown a greater interest in diseases such as Duchenne and DM1 in recent years. Sarepta brought several Duchenne treatments to market, and others such as Dyne and Vertex Pharmaceuticals have invested in DM1 therapies. Novartis, meanwhile, recently made a big bet on the market, completing a $12 billion buyout of Avidity.