CHeT News

Read full press release: https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-announces-fda-breakthrough-therapy-designation

WALTHAM, Mass., June 17, 2025 (GLOBE NEWSWIRE) -- Dyne Therapeutics, Inc. (Nasdaq: DYN), a clinical-stage company focused on delivering functional improvement for people living with genetically driven neuromuscular diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to DYNE-101 for the treatment of myotonic dystrophy type 1 (DM1). The company also announced an updated plan for obtaining U.S. Accelerated Approval for DYNE-101 in DM1 following a Type C meeting with the FDA and analysis of new long-term functional data.

“After our Type C meeting, we were granted Breakthrough Therapy Designation for DYNE-101 in DM1. We appreciate the FDA’s active engagement and guidance as we advance this promising program through the Accelerated Approval pathway in the U.S.,” said John Cox, president and chief executive officer of Dyne. “Based on feedback from the FDA, along with our 6-month and new 12-month efficacy data, we have submitted a revised protocol for the ongoing Registrational Expansion Cohort of the ACHIEVE trial with vHOT as the primary endpoint for potential Accelerated Approval.”

Accelerated Approval Pathway for DYNE-101 in DM1

• In May 2025, Dyne participated in a Type C meeting with the Center for Drug Evaluation and Research (CDER) at the FDA and discussed the path to regulatory approval, including U.S. Accelerated Approval, for DYNE-101 in DM1.
  • Dyne and FDA agreed that the next step toward Accelerated Approval was to submit for review the revised protocol for the Registrational Expansion Cohort of the ACHIEVE trial with video hand opening time (vHOT) as the primary endpoint, to serve as an intermediate clinical endpoint.
  • In June, Dyne submitted the revised protocol to the FDA.
• Dyne has revised the ongoing Registrational Expansion Cohort in the ACHIEVE trial as follows:

  • The primary endpoint is change from baseline in middle finger myotonia as measured by vHOT at 6 months, compared to placebo.

  • Secondary endpoints include change from baseline in splicing as measured by the composite alternative splicing index (CASI-22), muscle strength as assessed by Quantitative Muscle Testing (QMT), performance on both the 10-Meter Walk/Run Test (10MWR) and 5 Times Sit to Stand Test (5xSTS), and the Myotonic Dystrophy Health Index (MDHI) patient reported outcome measure, all at 6 months compared to placebo.

  • This cohort is expected to enroll 60 participants, randomized 3:1 to receive DYNE-101 6.8 mg/kg Q8W or placebo.

  • Additional clinical trial sites are being added, including sites in the U.S., to support enrollment.

• Dyne intends to use data from the Registrational Expansion Cohort and from the already enrolled patients in the multiple ascending dose (MAD) and ongoing long-term extension portions of the ACHIEVE trial to support a potential submission for Accelerated Approval in the U.S.

Accelerated Approval Milestones for DYNE-101 in DM1

• Dyne plans to complete enrollment in the Registrational Expansion Cohort in Q4 2025.
• Data from this cohort are planned for mid-2026 to support a potential U.S. Accelerated Approval submission in late 2026.
• Dyne plans to initiate a confirmatory Phase 3 clinical trial in Q1 2026.
• Dyne is also pursuing expedited approval pathways globally for DYNE-101.

New Long-term Data from Multiple Ascending Dose (MAD) Portion of ACHIEVE Trial

• Today, Dyne reported new long-term data from adult DM1 patients enrolled in the randomized, placebo-controlled MAD portion of the DYNE-101 ACHIEVE trial, including data from the 6.8 mg/kg Q8W cohort (n=6) at up to 12 months.
• At the registrational dose of 6.8 mg/kg Q8W, DYNE-101 demonstrated robust and sustained improvement in myotonia as measured by vHOT as well as sustained improvements across multiple other endpoints.
• These data support improvement in vHOT as an early indicator of clinical benefit with DYNE-101 in DM1 and its potential as an intermediate clinical endpoint for U.S. Accelerated Approval.
  • As previously disclosed, treatment with DYNE-101 led to an improvement in vHOT of 3.3 seconds as compared to placebo at 6 months.
  • New data demonstrated that mean improvements at 6 months were sustained at 12 months for vHOT, 10MWR, 5xSTS, MDHI and QMT, which demonstrated a 10% improvement in strength at 6 months, increasing to 20% at 12 months relative to baseline.
• Dyne also reported updated safety and tolerability data1 from 56 patients enrolled through the 6.8 mg/kg Q8W cohort of the ACHIEVE trial. DYNE-101 continued to demonstrate a favorable safety profile, and no related serious treatment emergent adverse events have been identified.

San Francisco, California - [August 1, 2024] - Effective treatment options to reduce mortality and prevent long-term morbidity caused by traumatic brain injury (TBI) are lacking in both military and civilian medicine. Over 30 clinical trials for TBI have failed, due in part to inadequate identification of unique patient characteristics for targeted therapy, lack of objective diagnostic and prognostic TBI biomarkers, and imprecise approaches to outcome measurement. This has prompted the call for a paradigm shift in the design of TBI Phase 2 trials. The result is a groundbreaking study just launched at UCSF to evaluate the effectiveness of experimental drug treatments in improving recovery outcomes for TBI patients. This research aims to compare the recovery progress of patients receiving the experimental treatment against a control group administered a placebo.

The aims of the study include:

• The use of FDA-approved oral drugs in an "off-label" capacity, meaning they are not currently approved specifically for TBI treatment.
• The study seeks to determine if these experimental treatments can significantly improve the recovery process for TBI patients.
• Researchers will conduct ongoing assessments to measure changes in recovery throughout the study period, potentially removing or adding drugs in the trial in an adaptive fashion. Adaptive trials are designed to enable changes to the trial after it has begun, without damaging the trial’s validity.

Key features of the protocol:

• Participant Profile: The study will enroll approximately 672 participants presenting at the emergency departments of up to 23 level 1 trauma center sites across the United States, with Glasgow Coma Scale (GCS) scores between 9 and 15 and positive head CT scans (e.g. evidence of bleeding), aiming for 504 completed follow-ups at 6 months.
• Timing: Treatment will begin within 24 hours of injury.
• Study Design: This Phase 2, multi-center, double-blind, placebo-controlled trial will employ an adaptive platform, precision medicine approach under a single multi-arm, multi-stage (MAMS) study framework. This will enable multiple treatments to be assessed simultaneously versus the more traditional “one drug-one trial” design.
• Treatment Interventions: Participants will be randomized to receive one of four treatments: Atorvastatin calcium (cholesterol-lowering drug), Minocycline hydrochloride (an antibiotic), Candesartan cilexetil (a blood pressure medication), or a matching placebo. These treatments have demonstrated benefit in animal models of TBI.
• Comprehensive Assessment includes:
  • The Glasgow Outcome Scale-Extended (GOSE-TBI) is the primary endpoint, and assesses functional impairment or recovery, from Week 2 to Month 3 postinjury; other clinical outcome assessments including a broad range of cognitive function, mental health, social participation, and symptom measurements will be collected as secondary endpoints.
  • Analysis of blood-based biomarker levels at intervals across study duration.
  • Performance of MRI at intervals across study duration.

University of California, San Francisco is the coordinating institution for the study, under the direction of corresponding principal investigator, Geoffrey T. Manley, MD PhD, Chief of Neurosurgery at Zuckerberg San Francisco General Hospital. The study will continue to roll out in the coming year to level 1 trauma centers that comprise the TRACK-TBI NETWORK. In addition to the recruitment sites, the study is also supported by research cores including the University of Pittsburgh Biospecimen Core led by Ava Puccio, PhD; UCSF Imaging Core led by Pratik Mukherjee MD PhD; Statistical Cores at the University of California, San Diego led by Sonia Jain, PhD and the University of Washington led by Nancy Temkin, PhD; and the Outcomes Core led by Joseph T. Giacino, PhD from Spaulding Rehabilitation Hospital and Mike McCrea, PhD and Lin Nelson, PhD at the Medical College of Wisconsin. The University of Rochester Center for Health + Technology (CheT) Clinical Trials Coordination Center (CTCC) led by Cynthia Casaceli MBA, and Melissa Kostrzebski MBA, MS, is performing Contract Research Organization support. This study, and future studies to be carried out under the adaptive platform trial program is funded by the U.S. Army Medical Materiel Development Activity (USAMMDA-Fort Detrick, MD) through the Medical Technology Enterprise Consortium (MTEC). Further support has been contributed by Abbott Laboratories. The trial is registered at https://clinicaltrials.gov/study/NCT05826912.

For more information, please contact: Brian Fabian, TRACK-TBI NET Program Manager, brian.fabian@ucsf.edu