Dyne Therapeutics is making strides in the development of novel therapies for neuromuscular diseases, with its lead candidate DYNE-101 showing promising results in the treatment of myotonic dystrophy type 1 (DM1). The company recently announced new clinical data from its Phase 1/2 ACHIEVE trial, demonstrating a compelling impact on key disease biomarkers and functional endpoints. In parallel, the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to DYNE-101, a significant step toward expediting its potential approval and availability to patients. These developments underscore Dyne's commitment to addressing unmet needs in genetically driven muscle diseases.
ACHIEVE Trial: Promising Efficacy and Safety Data
The Phase 1/2 ACHIEVE trial is a randomized, placebo-controlled, double-blind study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of DYNE-101 in adults with DM1. The trial incorporates a Multiple Ascending Dose (MAD) portion and a Registrational Expansion Cohort to support a potential submission for U.S. Accelerated Approval.
According to Dyne, DYNE-101 has demonstrated a favorable safety profile in the ACHIEVE trial. The majority of treatment emergent adverse events were mild or moderate, and no related serious treatment emergent adverse events have been identified. Approximately 855 doses have been administered, representing over 72-patient years of follow-up, with some patients being followed for up to 2.1 years.
Key findings from the ACHIEVE trial include:
- DMPK RNA Reduction: Analysis of muscle biopsy data from the 6.8 mg/kg Q8W cohort showed a substantial knockdown of DMPK RNA levels, the molecular target of DYNE-101.
- Splicing Correction: Significant splicing correction was observed at 3 months in the 6.8 mg/kg Q8W cohort, as measured by the Composite Alternative Splicing Index (CASI-22). This correction was associated with improvements in multiple functional endpoints.
- Myotonia Improvement: Early and sustained improvement in myotonia, as measured by video hand opening time (vHOT), was seen in the 6.8 mg/kg Q8W cohort, with deepening effects over time.
- Strength and Function: Functional measures, including the 5 Times Sit to Stand Test, Quantitative Myometry Testing (QMT), and the 10-Meter Walk/Run Test (10MWR), showed early and sustained clinical benefit at the 6.8 mg/kg Q8W dose.
- Patient-Reported Outcomes: Encouraging trends were observed in the Myotonic Dystrophy Health Index (MDHI), particularly in subscales assessing central nervous system disease manifestations.
"The ACHIEVE trial data represent a significant step forward and underscore the potential of DYNE-101 to address many of the most challenging symptoms experienced by individuals living with DM1," said Dr. James Lilleker, Neurologist, UK, and principal investigator in the ACHIEVE trial. "In addition to the favorable safety profile, I am particularly excited by the improvements observed in measures of strength and mobility, as well as effects on CNS manifestations suggested by the trends seen in the MDHI data. These data reflect clinically meaningful aspects of patients’ functional abilities and daily lives."
FDA Fast Track Designation
The FDA's Fast Track designation is designed to expedite the development and review of drugs that treat serious conditions and fill unmet medical needs. This designation offers several potential benefits, including more frequent meetings and communications with the FDA, rolling review of the Biologic License Application (BLA), and potential eligibility for Accelerated Approval and Priority Review.
"This Fast Track designation comes on the heels of robust clinical data from our ACHIEVE trial, which demonstrated substantial functional benefit for patients across a range of clinical measures and a compelling effect on the key disease biomarker of splicing correction," said Doug Kerr, M.D., Ph.D., chief medical officer of Dyne. "DM1 is a devastating disease with no approved therapies, and we are driven to deliver DYNE-101, a potentially transformative medicine, to patients as quickly as possible."
Clinical Development Plans and Regulatory Strategy
Dyne is planning to initiate a global placebo-controlled Registrational Expansion Cohort in the ACHIEVE trial, which will include approximately 32 patients at the 6.8 mg/kg Q8W dose. The primary endpoint for this cohort will be mean splicing correction at 3 months, as measured by CASI-22, supported by clinically meaningful measures of muscle strength and function. Dyne anticipates completing enrollment of the Registrational Expansion Cohort in mid-2025 and submitting for U.S. Accelerated Approval in H1 2026.
Advancing DYNE-251 for Duchenne Muscular Dystrophy
In addition to DYNE-101, Dyne is also advancing DYNE-251, an investigational therapeutic for Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. The Phase 1/2 DELIVER trial is ongoing, and Dyne is pursuing expedited approval pathways globally for DYNE-251 based on dystrophin as a surrogate endpoint. Data from the Registrational Expansion Cohort in the DELIVER trial are expected in late 2025, with potential for regulatory submissions in early 2026.
With a strong financial position, holding approximately $642 million in cash, cash equivalents, and marketable securities as of December 31, 2024, Dyne Therapeutics is well-positioned to continue its strategic approach to developing transformative therapies for genetically driven muscle diseases.
