Phase 1 trial of PepGen’s DM1 therapy delayed by FDA clinical hold
However, Phase 2 study of PGN-EDO51 for Duchenne MD cleared in Canada
The U.S. Food and Drug Administration (FDA) has placed a clinical hold on an application to launch a Phase 1 study of PGN-EDODM1, an experimental medicine by PepGen for people with myotonic dystrophy type 1 (DM1).
A clinical hold is an order issued by the FDA to delay a proposed clinical study or to suspend an ongoing investigation. The company will know the exact reasons for the clinical hold when it receives an official letter from the FDA some time within the next four weeks.
“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,” James McArthur, PhD, president and CEO of PepGen, said in a press release. “In parallel, we continue to pursue the advancement of PGN-EDODM1 into the clinic outside the U.S.”
DM1 is a type of muscular dystrophy that causes the muscles to become weaker over time and is characterized by myotonia — when muscles are unable to relax after a contraction. It occurs when a gene called DMPK contains repeated sequences that transcribe into a specific code known as CUG. The CUG repeats loop into the shape of hairpins.
These hairpin loops lead to errors in the way genetic information is read, which results in abnormal production of a protein called myotonic dystrophy protein kinase (DMPK). This protein is important for muscles to contract and relax.
PGN-EDODM1 is designed to deliver a small molecule, called an antisense oligonucleotide, that binds to the CUG repeats and corrects defects in RNA processing to generate a protein. This is expected to restore the production of fully working DMPK and allow the muscles to function properly again.
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.
Preclinical research shows PGN-EDODM1 eased myotonia
Earlier preclinical work showed that PGN-EDODM1 was well-tolerated by rodents and non-human primates when given at clinically relevant doses. In mice given a single dose of PGN-EDODM1, there was sustained easing of myotonia.
The company received the green light from Health Canada to move PGN-EDO51 into an open-label Phase 2 study, dubbed CONNECT1-EDO51, in which people with Duchenne muscular dystrophy will receive multiple ascending doses of the experimental medicine.
The clinical hold on the Phase 1 study of PGN-EDODM1 in the U.S. does not get in the way of launching CONNECT1-EDO51 in Canada, the company stated.
“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,” McArthur said.