DYNE-101 Receives FDA Fast Track Designation to Treat Myotonic Dystrophy

Author(s):

Kennedy Ferruggia, Assistant Editor

Key Takeaways

DYNE-101 targets DM1 by reducing toxic DMPK RNA, potentially halting or reversing disease progression through improved protein function.
The ACHIEVE trial is a phase 1/2 study assessing DYNE-101's safety and efficacy in DM1 patients, with multiple dosing cohorts.
Fast track designation follows orphan drug status, underscoring DYNE-101's potential as a transformative therapy for DM1.
The trial includes a placebo-controlled period, open label extension, and long-term extension, focusing on safety and muscle function outcomes.

The fast-track designation follows the FDA orphan drug designation that was granted for DYNE-101 in September 2023 for the same treatment population.

The FDA granted fast track designation to DYNE-101 (Dyne Therapeutics Inc) for the treatment of myotonic dystrophy type 1 (DM1), a rare, progressive, genetic disease that impacts skeletal, cardiac, and smooth muscle.¹

Muscular dystrophy. A group of diseases that cause progressive weakness and loss of muscle mass. abnormal genes interfere with the production of proteins needed to form healthy muscle - Image credit: Thipphaphone | stock.adobe.com

Image credit: Thipphaphone | stock.adobe.com

“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,” Doug Kerr, MD, PhD, chief medical officer of Dyne, said in a news release. “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.”¹

DM1 is estimated to affect over 40,000 US individuals and more than 74,000 individuals residing in Europe, with no approved therapy to aid disease progression. The autosomal dominant disease is caused by an abnormal trinucleotide expansion in the area of the dystrophia myotonica protein kinase (DMPK) gene, located close to the regulation region of a protein-coding gene, SIX5, that produces a transcription factor protein. Individuals with DM1 could experience myotonia and weakening of the heart muscles as the disease progresses, which could impact mobility, breathing, heart function, speech, digestion, vision, and cognition.^1,2

DYNE-101 is an experimental treatment for DM1 that utilizes an antisense oligonucleotide (ASO) conjugated to a fragment antibody (Fab) to specifically target and deliver the ASO to muscle tissue, where it aims to reduce the levels of toxic DMPK RNA. This leads to the release of splicing proteins, enabling the production of functional proteins, and potentially halting or reversing the progression of the disease, according to study authors.¹

A randomized, placebo-controlled, multiple-ascending dose (MAD) phase 1/2 ACHIEVE (NCT05481879) global clinical trial is ongoing, aimed to evaluate the safety and tolerability multiple intravenous doses of DYNE-101 among individuals with DM1, aged 18-49 years.^3,4

The study includes 4 periods—an 8-week screening, 24-week MAD placebo-controlled period, 24-week open label extension period, and a 96-week long-term extension period. The study will enroll more than 64 individuals across 4 cohorts of ascending doses of DYNE-101, with a primary outcome of number of participants with treatment-emergent adverse events and a secondary outcome of change from baseline in splicing, as well as measures of muscle strength and function.^3-5

Individuals included in the study will be randomly assigned to receive 1.8 mg/kg or 3.4 mg/kg every 4 weeks, as other participants will be randomly assigned to receive 6.8 mg/kg or 10.2 mg/mg every 4 or 8 weeks. However, all individuals will receive the highest safe and tolerable dose of DYNE-101 during the open label extension and long-term extension period, according to study authors.^3,4

The fast-track designation follows the FDA orphan drug designation that was granted for DYNE-101 in September 2023 for the same treatment population.⁵

“We believe DYNE-101 has the potential to be a transformative therapy which is why we designed the ACHIEVE trial to be registrational,” Wildon Farwell, MD, MPH, chief medical officer of Dyne, said in a news release. “We recognize the sense of urgency within the DM1 community and look forward to sharing initial data from the ACHIEVE trial.”⁵

REFERENCES

1. Dyne Therapeutics Receives FDA Fast Track Designation for DYNE-101 for the Treatment of Myotonic Dystrophy Type 1. BioSpace. News release. January 21, 2025. Accessed January 23, 2025. https://www.biospace.com/press-releases/dyne-therapeutics-receives-fda-fast-track-designation-for-dyne-101-for-the-treatment-of-myotonic-dystrophy-type-1

2. Myotonic Dystrophy (DM). Myotonic Dystrophy Association. Accessed January 23, 2025. https://www.mda.org/disease/myotonic-dystrophy

3. Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants With Myotonic Dystrophy Type 1 (ACHIEVE). ClinicalTrials.gov. October 31, 2024. Accessed January 23, 2025. https://clinicaltrials.gov/study/NCT05481879

4. ACHIEVE Trial, a Randomized, Placebo-Controlled, Multiple Ascending Dose Study of DYNE-101 in Individuals with Myotonic Dystrophy Type 1 (DM1). Myotonic Dystrophy Association. Accessed January 23, 2025. https://www.mdaconference.org/abstract-library/achieve-trial-a-randomized-placebo-controlled-multiple-ascending-dose-study-of-dyne-101-in-individuals-with-myotonic-dystrophy-type-1-dm1/

5. Dyne Therapeutics Receives FDA Orphan Drug Designation for DYNE-101 for the Treatment of Myotonic Dystrophy Type 1. Dyne Therapeutics. News release. September 20, 2023. Accessed January 23, 2025. https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-receives-fda-orphan-drug-designation-dyne-101.