IND Application Approved For DM1 Treatment
The FDA has approved the investigational new drug (IND) application, initiating the FREEDOM-DM1 Phase 1 study of PGN-EDODM1 in DM1 patients in the U.S.
What is DM1?
Myotonic dystrophy type 1 (AKA Steinert’s Disease) is a severe, progressive, and life-threatening disease that affects thousands of people worldwide. DM1 is the most prevalent form of the disease and affects approximately 40,000 people in the U.S. and 70,000 in the EU.
It is characterized by muscle weakness, myotonia (stiff or contracted muscles), and cardiac and respiratory abnormalities. Additionally, individuals with DM1 may experience excessive daytime sleepiness, fatigue, and issues with gastrointestinal or cognitive dysfunction. The average life expectancy for people living with DM1 is 45-60 years old. Currently, there are limited treatment options available, and existing therapies have not established significant clinical benefits for DM1 patients.
Investigational New Drug
PGN-EDODM1 is an oligonucleotide therapy developed to target the toxic RNA species responsible for DM1. DM1 is caused by an expansion of CUG repeats that form hairpin loops in the DMPK RNA. This leads to the sequestration of the MBNL1 protein, a crucial RNA processing factor. This results in mis-splicing events and abnormal expression of proteins that play critical roles in muscle and other systemic functions.
The goal of PGN-EDODM1 is to block the toxic CUG repeats, thereby liberating the MBNL1 protein and restoring functional downstream splicing and muscle function. Preclinical studies in a DM1 mouse model have shown promising results, with significant reversal of myotonia and correction of mis-splicing.
PepGen recently announced that the FDA has lifted the full clinical hold on the company’s DM1 program in the United States. This clearance allows PepGen to initiate the FREEDOM-DM1 Phase 1 study of PGN-EDODM1 in DM1 patients in the U.S. The study aims to evaluate the safety, tolerability, correction of mis-splicing of transcripts, and clinical functional outcome measures of PGN-EDODM1.
Phase 1 Study
The FREEDOM-DM1 study is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study. It will be conducted at multiple sites in both the U.S. and Canada. Three dose levels of PGN-EDODM1, namely 5 mg/kg, 10 mg/kg, and 20 mg/kg, will be evaluated in the study. The decision to advance to the next dose level will depend on the evaluation of safety data from previous cohorts.
PepGen’s preclinical studies with PGN-EDODM1 in a DM1 mouse model have shown promising results. In this model, the EDO technology achieved oligonucleotide muscle concentrations of 6
nM of PGN-EDODM1, resulting in 76% reversal of myotonia and 68% correction of mis-splicing. Multiple doses further increased the correction rates to 99% for both measures.
Based on these encouraging preclinical results, PepGen anticipates obtaining proof-of-concept data in DM1 patients in 2024. This data will include transcript splicing and clinical outcome measures at the 5 mg/kg PGN-EDODM1 dose level. The company’s collaboration with the FDA and the clearance of the IND mark significant milestones in the development of PGN-EDODM1 for individuals worldwide living with DM1.The clearance of the FDA hold on the DM1 program and the initiation of the FREEDOM-DM1 study mark significant milestones in the journey to transform the treatment of DM1.
For more information on Myotonic Dystrophy type 1 and other musculoskeletal diseases click here checkrare.com/diseases/musculoskeletal-diseases/
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