Efficacy of AMO-02 (tideglusib) in Myotonic Dystrophy Type 1 (DM1)

Michael Snape, PhD, Chief Science Officer at AMO Pharma, discusses the efficacy of AMO-02 (tideglusib) for myotonic dystrophy type 1 (DM1).
DM1 is a genetic disease affecting the muscles and other body systems. Three forms of DM1 may present: the mild form, the classic form, and the congenital form. This disease is characterized by progressive muscle loss and weakness. People with myotonic dystrophy usually have prolonged muscle tensing and are not able to relax certain muscles after use. The severity of the disease may vary among affected people, even among members of the same family. Myotonic dystrophy is caused by genetic changes in the DMPK gene.
Tideglusib is an investigational therapy being developed for the potential treatment of DM1. As Dr. Snape explains, tideglusib has a dual mechanism: (1) disrupting the pathogenic RNA repeat in DM1, and (2) inhibiting excess GSK3β, an intracellular regulatory kinase that is dysregulated in DM1.
The REACH-CDM study is a Phase 2/3 double-blind, placebo controlled, randomized study testing the efficacy of tideglusib in patients ages 6 to 16 years with congenital DM1. Patients in this study showed improvements in a variety of measures; however, positive results for the primary endpoint were greatly observed in the placebo group as well. Therefore, this study did not meet its primary endpoint of a significant improvement over placebo based on a physician completed rating scale.
Due to improvements observed over placebo in secondary endpoints, the U.S. Food and Drug Administration has allowed the company to go forward with a phase 3 trial. This study will test the efficacy and safety of tideglusib in adult patients with adult-onset DM1. Results from the new study will supplement the results in the REACH-CDM study and hopefully lead to approval of the therapy.
Dr. Snape also discusses the challenges of developing therapies and studies for rare diseases that vary greatly in their clinical presentations, attributing this as one of the reasons for the delay in approval of tideglusib.
Chapters:
Intro 00:00
Pathophysiology of Myotonic Dystrophy Type 1 00:11
AMO-02 For DM1 Treatment 2:58
Phase 2/3 REACH-CDM Clinical Trial 4:24
Effect of Symptom Variance on Study 10:09

[@vampyros1]

I really appreciate this overview of advances in potential therapies for this disease, and I’ll look forward to any updates you present on this channel. Thank you Dr.!