Hold Lifted on ASO for Myotonic Dystrophy Type 1, Trial to Initiate in the US


The FDA previously placed the trial on clinical hold for undisclosed reasons.

The FDA has lifted a clinical hold on PepGen’s Investigational New Drug (IND) application for its FREEDOM-DM1 phase 1 study of PGN-EDODM1 antisense oligonucleotide (ASO) for the potential treatment of Myotonic Dystrophy Type 1 (DM1), which the company will initiate presently.1

“We have worked closely with the FDA to resolve their questions expeditiously and are pleased that the clinical hold on our DM1 program in the United States has been lifted. Our novel PGN-EDODM1 approach targets the toxic RNA species responsible for the disease, and the strength of our Enhanced Delivery Oligonucleotide (EDO) safety preclinical package has enabled us to launch this study in both the US and internationally at doses that we believe could provide a clinically meaningful benefit to patients. We are very pleased after review of our existing safety data that the FDA agreed with our proposed starting dose of 5 mg/kg, moving up to 10 mg/kg and 20 mg/kg,” James McArthur, PhD, president and chief executive officer, PepGen, said in a statement.1

The randomized, double-blind, single ascending dose, placebo-controlled FREEDOM-DM1 study will launch in the US with target dose levels of 5 mg/kg, 10 mg/kg and 20 mg/kg and evaluate PGN-EDODM1 for safety and tolerability, correction of mis-splicing of transcripts, and clinical functional outcome measures. Dose levels will ascend pending positive safety data from the previous dose cohort. The trial previously launched in Canada in September 2023.The FDA placed the IND on clinical hold in May 2023, however the reasons for the hold were never publicly disclosed.2

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PepGen expects to gather the preliminary data from the first dose level in 2024.1 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 US, and 70,000 in the European Union have DM1 and the average life expectancy for people living with DM1 is 45-60 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,” McArthur added.1

1. PepGen Inc. announces FDA has lifted the clinical hold on its investigational new drug application for FREEDOM-DM1 phase 1 study of PGN-EDODM1 for Myotonic Dystrophy Type 1 (DM1). News release. PepGen. October 12, 2023. https://www.biospace.com/article/releases/pepgen-inc-announces-fda-has-lifted-the-clinical-hold-on-its-investigational-new-drug-application-for-freedom-dm1-phase-1-study-of-pgn-edodm1-for-myotonic-dystrophy-type-1-dm1-/
2. PepGen Inc. announces clinical hold in the U.S. on IND application to initiate a phase 1 study of PGN-EDODM1 for Myotonic Dystrophy Type 1 (DM1). News release. PepGen. May 30, 2023. https://investors.pepgen.com/news-releases/news-release-details/pepgen-inc-announces-clinical-hold-us-ind-application-initiate
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