DYNE-101 is an investigational therapeutic being evaluated in the Phase 1/2 global ACHIEVE clinical trial for people living with DM1[^2^].
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This therapy consists of an antigen-binding fragment antibody (Fab) conjugated to an antisense oligonucleotide (ASO). The goal of DYNE-101 is to enable targeted delivery to muscle tissue. Thus, reducing toxic DMPK RNA in the nucleus and facilitating normal mRNA processing and translation of normal proteins, potentially halting or reversing the disease[^2^].
Myotonic Dystrophy Type 1
Myotonic dystrophy type 1 (DM1) is a rare genetic disease that affects skeletal, cardiac, and smooth muscle. It is characterized by a progressive weakening of major muscle groups. This leads to mobility issues, breathing difficulties, heart problems, speech impairments, and more. Currently, there are no approved disease-modifying therapies for DM1. However, there is hope on the horizon with the development of DYNE-101. DYNE-101 is an investigational therapeutic that shows promise in treating this devastating disease. In a significant breakthrough, Dyne Therapeutics, a clinical-stage muscle disease company, announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for DYNE-101 for the treatment of DM1.
DYNE-101 targets the underlying cause of DM1 by addressing the abnormal trinucleotide expansion in the DMPK gene. This leads to the formation of toxic RNA clusters in the nucleus[^2^]. By reducing the levels of toxic DMPK RNA, DYNE-101 aims to restore normal cellular function and alleviate DM1 symptoms. Preclinical studies have demonstrated the efficacy of DYNE-101 in reducing nuclear foci, correcting splicing in patient cells, and reversing myotonia in disease models[^2^].
The ACHIEVE Clinical Trial
The Phase 1/2 global ACHIEVE clinical trial is a crucial step in evaluating the safety and efficacy of DYNE-101 in patients with DM1[^2^]. The trial consists of a multiple ascending dose (MAD) randomized placebo-controlled period, an open-label extension, and a long-term extension. Approximately 72 adult patients with DM1, aged 18 to 49 years, are expected to participate in the trial[^2^].
The primary endpoints of the ACHIEVE trial are safety and tolerability, while secondary endpoints include pharmacokinetics, pharmacodynamics, and measures of muscle strength and function[^2^]. The trial design has been carefully crafted to provide robust data on the safety and efficacy of DYNE-101, with initial data expected to be reported in the second half of 2023[^2^].
DM1 is a rare genetic disease that severely impacts the lives of those affected. The announcement of FDA orphan drug designation for DYNE-101 brings hope to the DM1 community. This investigational therapeutic shows promise in addressing the underlying cause of DM1 by reducing toxic RNA levels and potentially halting or reversing the disease.
The Phase 1/2 ACHIEVE clinical trial will provide valuable data on the safety and efficacy of DYNE-101, with initial results expected in the second half of 2023. If successful, DYNE-101 could become a game-changer in the treatment of DM1, offering new hope and improved quality of life for patients.
For more information on Myotonic Dystrophy type 1 and other musculoskeletal diseases click here checkrare.com/diseases/musculoskeletal-diseases/
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