The FDA has placed a partial clinical hold on PepGen’s Phase 2 FREEDOM2-DM1 trial of PGN-EDODM1 for myotonic dystrophy type 1 due to questions related to preclinical pharmacology and toxicology studies.
Written By: Marka Sheshi, PharmD
Reviewed By: Pharmacally Editorial Team
PepGen Inc. announced that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on the company’s FREEDOM2-DM1 Phase 2 clinical trial evaluating PGN-EDODM1 in patients with myotonic dystrophy type 1 (DM1).
The FREEDOM2 study is a randomized, placebo-controlled multiple ascending dose (MAD) trial designed to evaluate the safety and activity of the investigational therapy in people living with DM1.
According to the company, the FDA’s questions relate to previously submitted preclinical pharmacology and toxicology data, the agency did not raise concerns about the blinded clinical data from the Phase 1 FREEDOM trial that had earlier supported the initiation of the FREEDOM2 study in the United States.
PepGen said it is working closely with the regulator and has begun submitting additional analyses, including recently unblinded data from the FREEDOM study, to address the agency’s questions and facilitate the resolution of the partial hold.
Despite the regulatory pause in the United States, clinical development continues in several other regions. PepGen recently received regulatory clearance to open the FREEDOM2 trial in New Zealand, Australia, and South Korea.
Following a recommendation from the independent Data Safety Monitoring Board to escalate dosing, patients are currently receiving the 10 mg/kg dose in Canada and the United Kingdom. No patients in the United States have been enrolled in the FREEDOM2 trial to date.
Participants from the earlier FREEDOM study and the ongoing FREEDOM2 trial in Canada are transitioning into an Open Label Extension (OLE) study designed to assess longer-term safety and outcomes.
PepGen has also secured regulatory clearance for the OLE study in the United Kingdom and plans to expand the extension study to all regions where the FREEDOM2 trial is active.
The company expects to report initial data from the 5 mg/kg cohort of the FREEDOM2 study in the first quarter of 2026, followed by results from the 10 mg/kg cohort in the second half of 2026.
PGN-EDODM1 is PepGen’s investigational therapy being developed to treat myotonic dystrophy type 1, a genetic neuromuscular disorder caused by toxic CUG repeat expansions in the DMPK gene. The therapy uses the company’s proprietary Enhanced Delivery Oligonucleotide (EDO) technology to deliver a therapeutic oligonucleotide designed to restore the normal activity of MBNL1, an RNA-splicing protein that becomes trapped by the abnormal RNA repeats in DM1.
By binding to the expanded CUG repeats and disrupting their interaction with MBNL1, PGN-EDODM1 aims to free the protein and correct downstream mis-splicing events while allowing normal DMPK transcripts to continue functioning within the cell.
PGN-EDODM1 has received Orphan Drug and Fast Track designations from the FDA for the treatment of DM1, highlighting the potential importance of the therapy for patients with this rare and currently untreatable genetic disorder. The European Medicines Agency has also granted the candidate Orphan Designation.
References
PepGen. Regulatory Update on FREEDOM2 Clinical Trial Evaluating PGN-EDODM1 in Myotonic Dystrophy Type 1. Official Press Release. March 4, 2026. https://investors.pepgen.com/news-releases/news-release-details/pepgen-announces-regulatory-updates-freedom2
A Clinical Study of PGN-EDODM1 in People With Myotonic Dystrophy Type 1 (FREEDOM2-DM1), ClinicalTrials.gov ID NCT06667453, https://clinicaltrials.gov/study/NCT06667453
About Writer
Marka Sheshi | Doctor of Pharmacy
Driven by a deep commitment to clinical excellence, research integrity, and impactful medical writing. With a strong foundation in pharmacotherapy and patient safety, specializes in transforming complex scientific evidence into authoritative, publication-ready content. Passionate about advancing healthcare through precise, evidence-based communication that informs practice, strengthens research visibility, and improves patient outcomes.