The FDA has put a partial clinical hold on PepGen’s phase 2 muscle wasting trial after reviewing preclinical data, continuing the stop-start advance of the program. Guggenheim Securities analysts blamed the hold on an “understaffed FDA.”
FDA officials applied the partial hold to Freedom2, a phase 2 study that is comparing PGN-EDODM1 to placebo in patients with myotonic dystrophy type 1 (DM1). PGN-EDODM1 uses PepGen technology to deliver an oligonucleotide. By restoring the normal splicing function of a protein, the oligonucleotide could selectively and directly address the genetic defect underlying DM1.
PepGen’s efforts to test that idea in humans have been slowed by FDA actions. The agency put a clinical hold on a planned phase 1 trial back in 2023. Having persuaded the FDA to lift the phase 1 hold, PepGen has now been told to pump the brakes on its phase 2 study. The biotech’s share price fell 18% to $5.55 in after-hours trading Wednesday, March 4.
Guggenheim analysts titled their note about the partial hold “understaffed FDA strikes again.” PepGen leaders told the analysts the hold relates to drops in blood pressure and temperature that were seen in mouse models—but not in nonhuman primates or humans.
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The analysts said the faster infusions given to mice cause higher maximum drug concentrations, leading to mouse-specific adverse events. Using a port to slow the infusion rate eliminates the effect in mice, the analysts said. PepGen leaders told the analysts the FDA has had the data since 2024, a period that covers the agency’s authorization to give patients doses of up to 20 mg/kg in the phase 1 trial.
PepGen is submitting additional analyses, including the recently unblinded phase 1 data, as it works with the FDA to quickly address the questions. The biotech has yet to commit to a timeline for resolving the hold. No other regulators have raised concerns about the data, the analysts said.
The company has received clearance to start the trial in South Korea, Australia and New Zealand and is giving the 10-mg/kg dose in the U.K. and Canada. Four patients have received the 10-mg/kg dose. PepGen expects to share 5-mg/kg data in the first quarter of the year and 10-mg/kg data in the second half. Based on safety data, the company may start a 12.5-mg/kg cohort.
The FDA put the biotech’s Duchenne muscular dystrophy trial on hold in 2024. PepGen dropped the asset in response to efficacy data last year.