The FDA has put a stop to U.S. initiation of PepGen’s Phase II trial for its Duchene muscular dystrophy treatment. The company faced the same hurdle for an earlier neuromuscular candidiate in 2023.
PepGen is once again facing a clinical hold in the U.S. for one of its neuromuscular disorder therapies. This time, it’s an oligonucleotide drug for Duchenne muscular dystrophy.
In May 2023, PepGen’s Phase I study of PGN-EDODM1 for patients with myotonic dystrophy type 1 (DM1) was placed on hold by the FDA in the U.S. The trial had been expected to get underway in the first half of that year. PepGen was able to get the trial going in other jurisdictions while the hold was in place, and the hold was eventually lifted in October 2023 after the FDA reviewed safety data and cleared the dose escalation strategy for the Phase I trial. Dosing began in December 2023, with initial data due to readout in the first quarter of 2025.
But now, PepGen is facing another speedbump in its clinical research operation. The FDA has halted the U.S. initiation of the Phase II CONNECT2-EDO51 for PGN-EDO51 in patients with DMD. PepGen provided few details in its Monday release, noting that the FDA is due to send a more detailed hold letter within 30 days. The mid-stage trial is already open in the U.K. and is enrolling in Canada.
“We intend to work closely with the FDA to address their questions on our application to initiate CONNECT2 as expeditiously as possible,” said Paul Streck, head of R&D of PepGen.
PepGen’s shares declined 17% to $3.86 on Monday morning before the markets opened. A similar 18% slide happened after the May 2023 hold was announced.
With few details to go on, Stifel’s analysts noted that PepGen recently reported that two patients in the portion of the trial outside the U.S. had mild and asymptomatic hypomagnesemia that was treated with supplementation. Magnesium deficiency is a known safety concern for peptide conjugates and has previously ended a program from PepGen competitor Sarepta Therapeutics, Stifel said. The hold could be unrelated, but the FDA’s action is an “overhang and valid concern” for investors.
“[PepGen] has maintained that their safety’s differentiated here, and we think they have a good case—and the clinical hold could very well be over something small, like a protocol/monitoring nuance,” the Stifel team wrote Monday morning.
PGN-EDO51 moved into the Phase II trial after earlier data from the CONNECT1 study showed a favorable safety profile. PepGen had expected to open the trial in the U.S. by the end of the year subject to regulatory approval, according to its third quarter earnings report. The drug targets exon 51, which is a validated target for DMD therapies present in about 13% of patients.
