PepGen has bowed to the inevitable and paused plans to get its second oligonucleotide therapy into the clinic in any country while it continues to wait for the post to deliver an FDA clinical hold letter.
The company announced two weeks ago that the regulator had sent a clinical hold notice in response to PepGen’s request to launch a phase 1 study in the U.S. of PGN-EDODM1 in myotonic dystrophy type 1, a genetic disorder that can cause muscle loss and weakness. At the time, the biotech said that while it waited to receive a formal hold letter setting out the FDA's objections, it would "continue to pursue the advancement of PGN-EDODM1 into the clinic outside the U.S."
PGN-EDODM1 consists of PepGen’s cell-penetrating peptide conjugated to a steric-blocking oligonucleotide cargo. In December, the biotech touted preclinical data showing the therapy was well tolerated in rodent and nonhuman primates. It also didn’t degrade DMPK transcripts, a potentially important safety benefit, in studies of patient cells, the company noted at the time.
But in a postmarket release yesterday, PepGen said it was withdrawing its plans to launch a phase 1 trial of the candidate in the first half of the year “in any geography.” With only weeks to go until we reach the year’s endpoint, it may seem that the company is stating the obvious, but it’s a reminder of the clinical limbo the candidate will remain in until the company can begin to address the regulator’s concerns.
“After careful consideration, we decided to pause additional regulatory filings for clearance to initiate a phase 1 study of PGN-EDODM1 in order to address the official hold letter once received from the FDA,” said CEO James McArthur, Ph.D., in the release. “We will continue to work closely with the FDA to lift the clinical hold whilst we remain fully committed to initiating a phase 1 study of PGN-EDODM1 as quickly as feasible.”
McArthur added that the company also “remain[s] very focused” on pushing ahead with a phase 2 trial in Canada of its lead program PGN-EDO51, a therapeutic oligonucleotide that targets exon 51 to treat a subset of Duchenne muscular dystrophy patients. Like Sarepta Therapeutics' Exondys 51, the drug is designed to mask exon 51 and thereby enable patients to produce the functional dystrophin needed to strengthen muscle fibers.