FDA Places Clinical Hold on PepGen’s Application to Initiate a Phase 1 Study in DM1

Rare Daily Staff

The U.S. Food and Drug Administration notified PepGen’s that it was placing a clinical hold on its Investigational New Drug Application to initiate a phase 1 study of PGN-EDODM1 in patients with Myotonic Dystrophy Type 1.

The FDA indicated its intention to provide an official clinical hold letter to PepGen stating the reasons for the clinical hold within 30 days.

“We are disappointed to receive a clinical hold notice on our planned PGN-EDODM1 study in the U.S., and we will work closely with the FDA to lift the hold as quickly as possible,” said James McArthur, president and CEO of PepGen. “In parallel, we continue to pursue the advancement of PGN-EDODM1 into the clinic outside the U.S. We remain well-capitalized to fund the continued development of both EDO51 and EDODM1, investigational treatments that may have life-changing impact on individuals with neuromuscular disorders.”

Myotonic dystrophy type 1 (DM1) is a progressive multisystemic disease that causes myotonia, or difficulty relaxing muscles, progressive muscle weakness and often other symptoms such as cataracts, heart conduction defects, endocrine changes including diabetes, cognitive issues and daytime sleepiness. Symptoms and onset present uniquely to each person affected and vary from minor muscle pain to serious respiratory and cardiac issues. DM1 is caused by toxic repeat sequences in the RNA that bind to a protein that is needed to correctly process a wide range of other RNAs. Misprocessing of RNAs leads to a wide range of symptoms. Current treatments, such as heart medications and medications to treat cramping, can help people with DM1 manage symptoms, but there are currently no approved disease-modifying treatments.

PGN-EDODM1 is an Enhanced Delivery Oligonucleotide peptide conjugated to a therapeutic oligonucleotide, for the treatment of DM1. On their own, oligonucleotide therapeutics are not readily distributed to heart and skeletal muscle, the key affected tissues in neuromuscular diseases like DM1. PepGen’s Enhanced Delivery Oligonucleotide technology allows it to optimize tissue and cell penetration in key muscle targets.

The company said the clinical hold in the U.S. placed on PGN-EDODM1 does not impact the CONNECT1-EDO51 study which has been cleared to proceed in Canada.

Photo: James McArthur, president and CEO of PepGen