A phase 1 study for PepGen’s myotonic dystrophy therapy has been cleared for launch in the U.S. after a five-month FDA clinical hold.
The Boston-based company announced the lifting of the hold after market close Wednesday, noting that the investigational new drug application for PGN-EDODM1 has been approved and the FREEDOM-DM1 trial is now good to go.
PGN-EDODM1 is being developed for myotonic dystrophy type 1 (DM1), a genetic muscular dystrophy disorder that affects 40,000 people in the U.S. It causes muscle weakness and wasting, cardiac and respiratory abnormalities and can shorten a person’s lifespan. The disorder is caused by a mutation in the DMPK gene. PGN-EDODM1 consists of PepGen’s cell-penetrating peptide conjugated to a steric-blocking oligonucleotide cargo.
PepGen ran into trouble in May when the FDA blocked the biotech’s attempt to get the oligonucleotide therapy into the clinic. Few details were released about the nature of the agency’s concerns, but the issue seems to have revolved around dosing.
CEO James McArthur, Ph.D., said a review of existing safety data convinced the FDA to approve a proposed starting dose of 5 mg/kg, moving up to 10 mg/kg and then 20 mg/kg. PepGen believes this dosing strategy could provide a clinically meaningful benefit for patients.
While sorting out the FDA issues, PepGen managed to get the FREEDOM-DM1 trial off the ground in Canada, where regulators approved an application in September.
The trial is a randomized, double-blind, placebo-controlled, single ascending dose study, that will assess safety and tolerability, the correction of mis-splicing of transcripts and clinical functional outcome measures, the company explained.
Preclinical data in mice showed that PGN-EDODM1 spurred a 76% reversal of myotonia, an impairment of muscle relaxation, and 68% correction of mis-splicing. In DM1, a key RNA processing factor is sequestered resulting in mis-splicing events that can lead to the impairment of many critical muscular and systemic functions. PGN-EDODM1 aims to free up the MBNL1 protein and restore splicing, and in turn, the impaired functions.
PepGen is also developing PGN-EDO51 for patients with exon 51 amenable Duchenne muscular dystrophy. Canada is also the destination for the phase 2 CONNECT1-EDO51 study, which is expected to produce proof-of-concept and safety data in mid-2024.
The company reported cash and equivalents of $147 million at the end of the second quarter, which is still expected to last into 2025.