ASO Fast Tracked for Myotonic Dystrophy


PGN-EDODM1 is being evaluated in the US and Canada in a phase 1 trial.

The FDA has granted Fast Track designation to PepGen’s PGN-EDODM1, an investigational peptide-conjugated antisense oligonucleotide (ASO) candidate for the treatment of myotonic dystrophy type 1 (DM1).1

“Receiving Fast Track designation from the FDA for PGN-EDODM1 is a significant milestone in our efforts to deliver a potentially transformative therapy to the DM1 community,” James McArthur, PhD, President and chief executive officer, PepGen, said in a statement.1 “Patients with DM1 currently have no available treatment options that target the root cause of the disease, which leads to progressive neuromuscular symptoms and reduction in life expectancy. Following robust preclinical data, we are now evaluating PGN-EDODM1 in the ongoing FREEDOM-DM1 Phase 1 trial and expect to report preliminary data later this year. We believe that PGN-EDODM1 has the potential to be disease-modifying and improve outcomes for patients living with DM1.”

PGN-EDODM1 is currently being evaluated in the phase 1 FREEDOM-DM1 trial, a randomized, placebo-controlled, single-ascending dose study. The trial, which dosed its first patient in December 2023, is currently being conducted in Canada, with sites expected to open in the United States soon.2 It expects to enroll 24 participants. The FDA previously placed a clinical hold on the trial, which was lifted in October 2023.3 PepGen expects to gather the preliminary data from the first dose level from the FREEDOM-DM1 trial in 2024.

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“We are pleased to announce we have dosed the first patient in our FREEDOM-DM1 clinical trial, which marks a significant milestone in our commitment to developing transformative therapies with potentially meaningful clinical outcomes for people living with DM1. We anticipate proof-of-concept data in patients in 2024, including safety, transcript splicing and clinical outcome measures, at the 5 mg/kg PGN-EDODM1 dose level,” McArthur said at that time.2 “We are also excited to announce the receipt of regulatory clearance to evaluate PGN-EDODM1 from the UK MHRA, marking the third obtained following clearances from the US Food and Drug Administration and Health Canada. We look forward to continuing our progress and remain steadfast in our dedication to the development of PGN-EDODM1 for individuals around the globe who are living with DM1.”

PGN-EDODM1 is an investigational peptide-conjugated ASO designed to liberate MBNL1 protein, which is sequestered in patients with DM1, and to restore functional downstream splicing, muscle, and other functions. Around 40,000 people in the United States and 70,000 in the European Union have DM1, with an average life expectancy of 45 to 60 years old.

“In a preclinical DM1 mouse model, where EDO technology achieved oligonucleotide muscle concentrations of 6 nM of PGN-EDODM1, we observed 76% reversal of myotonia and 68% correction of mis-splicing. This was increased to 99% correction of both measures following multiple doses. Based on these preclinical results, we anticipate proof-of-concept data in patients in 2024, including transcript splicing and clinical outcome measures, at the 5 mg/kg PGN-EDODM1 dose level in DM1 patients. With clearance of our IND from the FDA, we are eager to open study sites in the U.S. to accelerate the development of PGN-EDODM1 for individuals worldwide living with DM1,” MacArthur previously said.3

1. PepGen Receives U.S. FDA Fast Track Designation for PGN-EDODM1 for the Treatment of Myotonic Dystrophy Type 1. News release. PepGen. February 20, 2024.
2. PepGen Announces First Patient Dosed in Phase 1 FREEDOM-DM1Clinical Trial of PGN-EDODM1 for Myotonic Dystrophy Type 1 (DM1). News Release. Published December 18, 2023. Accessed January 19, 2024.
3. PepGen Inc. announces FDA has lifted the clinical hold on its investigational new drug application for FREEDOM-DM1 phase 1 study ofPGN-EDODM1 for Myotonic Dystrophy Type 1 (DM1). News release. PepGen. October 12, 2023. Accessed January 18, 2024.
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