Recent Advances in Myotonic Dystrophy Type 1 Treatment Show Promise

Myotonic dystrophy type 1 (DM1), a form of muscular dystrophy affecting approximately 140,000 people in the United States, may soon have its first disease-modifying treatment. Recent clinical trial results from multiple pharmaceutical companies have shown significant progress in addressing this unmet medical need.

Oligonucleotide Therapies Lead the Way

Dyne Therapeutics has emerged as a frontrunner in the DM1 treatment space with its recent announcement of positive Phase I/II trial results for DYNE-101. This antisense oligonucleotide, fused with a fragment antibody that binds to the transferrin receptor 1 in muscles, demonstrated DMPK RNA level reductions and improvements in several clinical assessments.

The ACHIEVE trial identified 6.8 mg/kg every 8 weeks as the optimal dose for future studies. Dyne plans to initiate a global registrational expansion cohort, potentially supporting an FDA Accelerated Approval submission in the first half of 2026.

Avidity Biosciences is not far behind with its antibody oligonucleotide conjugate, AOC 1001 (del-desiran). The company recently announced positive long-term data from the Phase II MARINA-OLE trial, showing reversal of disease progression across multiple endpoints compared to a matched natural history study population over one year. Avidity aims to submit marketing applications in 2026 and is currently conducting the Phase III HARBOR trial.

Repurposed Drugs Show Potential

While oligonucleotide-based therapies are making significant strides, several repurposed drugs are also undergoing Phase III trials for DM1 treatment. Metformin, a biguanide approved for type 2 diabetes mellitus, has shown promise in increasing the 6-minute walking distance for DM1 patients in Phase II trials.

AMO Pharma's tideglusib (AMO-02), a glycogen synthase kinase 3 beta inhibitor, is advancing to Phase III trials despite not reaching its primary endpoint in the Phase II/III REACH-CDM trial. The drug demonstrated clinically and statistically significant benefits in various functional and objective assessments.

Lupin is exploring the use of mexiletine, a class I antiarrhythmic drug, in a new prolonged-release oral suspension formulation for DM1 treatment. The company is conducting Phase III HERCULES and ATLAS trials, despite mixed results in earlier studies.

The Road Ahead

As the DM1 treatment landscape evolves, antibody-oligonucleotide conjugates appear to be more effective at targeting the genetic source of the disease compared to small molecules and repurposed drugs. However, the field remains challenging, as evidenced by Ionis Pharmaceuticals' discontinued development of IONIS-DMPK-2.5Rx in 2017 due to inadequate muscle concentration levels in Phase I/II trials.

With multiple companies advancing their candidates through late-stage clinical trials, new disease-modifying treatments for DM1 could potentially reach the market within the next three to four years. As these developments unfold, the pharmaceutical industry continues to demonstrate its commitment to addressing the unmet needs of patients with rare genetic disorders.