PepGen slumps as FDA places hold on lead drug

Shares in PepGen were down more than 21% after the FDA placed a partial clinical hold on its lead drug PGN-EDODM1, for rare genetic muscle disorder myotonic dystrophy type 1 (DM1).

The move affects PepGen's FREEDOM2-DM1 trial of PGN-EDODM1, an oligonucleotide-based therapy for DM1 designed to restore the normal function of a protein (MBNL1) that is dysregulated in the disorder, leading to progressive muscle wasting, weakness, and an inability to relax muscles (myotonia).

PepGen said the clinical hold relates to previously submitted preclinical pharmacology and toxicology studies and does not involve its earlier, phase 1 FREEDOM trial, which was submitted to the FDA to get approval to start the phase 2 study.

The regulatory action comes as the FDA is causing jitters among rare disease therapy developers with recent actions, including requiring a new clinical trial for uniQure's Huntington's disease therapy AMT-130 and the recent rejections of Biohaven's troriluzole for spinocerebellar ataxia (SCA) and Atara/Pierre Fabre's Ebvallo for post-organ transplant malignancy.

Last week, the US Senate Special Committee on Aging examined allegations of inconsistent and overly cautious regulation of rare disease therapies by the FDA under the current administration.

News of the clinical hold came as PepGen was granted regulatory clearance to start dosing patients in South Korea, Australia, and New Zealand, in addition to open-label extensions to the study for the UK and Canada cohorts. As yet, no US patients have been enrolled into the trial, so the partial hold will delay the collection of data to support any future US filing.

"As part of its ongoing dialogue with the FDA, the company is submitting additional analyses, including the recently unblinded FREEDOM data, and is committed to working with the FDA to address their questions as quickly as possible," said PepGen in a statement.

The company said it remains on course to report results from the 5 mg/kg dosing group before the end of this month, with data from the 10 mg/kg group expected in the latter half of this year.

Apparently shrugging off news of the clinical hold, PepGen's chief executive, James Macarthur, said the company is "entering this new year with strong momentum and a clear path toward potentially delivering a meaningful new treatment for the DM1 community."

PepGen has just reported its 2025 financial results, ending the year with $148.5 million in cash that it says will fund operations into the second half of 2017.