Phase 3 Trial for Myotonic Dystrophy Agent AMO-02 To Begin Following FDA Meeting


Despite failing to meet the primary end point, AMO-02 achieved clinically and statistically significant benefit in various functional and objective assessments in the phase 2/3 REACH-CDM trial.

Alan Rubino, the executive chair at AMO Pharma

Alan Rubino

Credit: AMO Pharma

Following a recent meeting with the FDA, AMO Pharma announced it will conduct a phase 3 clinical trial to evaluate the efficacy and safety of AMO-02, an investigational therapy, for the treatment of type 1 myotonic dystrophy (DM1), in adult patients with adult-onset DM1. Data from that study, along with findings from the phase 2/3 REACH-CDM trial (NCT05004129) are expected to serve as evidence for a future submission for approval of AMO-02 in DM1.1

In the meeting, the agency reviewed data from REACH-CDM, a double-blind, placebo-controlled, randomized study that assessed the efficacy and safety of treatment with AMO-02 in pediatric patients with congenital DM1. The FDA also gave feedback on the design of the new phase 3 clinical trial for adult patients with adult onset DM1, in which the outcome measures will be similar to those that showed benefit in REACH-CDM. Further analyses reviewed by the agency indicated that there is sufficient evidence to support the continued development AMO-02 for the treatment of DM1.

Top Clinical Takeaways

  • FDA discussions pave the way for a phase 3 trial of AMO-02 in adult-onset DM1, indicating progress in DM1 treatment.
  • AMO Pharma expresses confidence in the potential of AMO-02 to advance DM1 therapy across age groups.
  • The upcoming trial aims to build on previous findings, aligning outcome measures with those demonstrating efficacy in patients with pediatric DM1.

"We are pleased with the outcome of the productive discussions we had with the FDA regarding next steps for AMO-02 and continue to feel strongly that this innovative therapy can represent a significant advance in the treatment of patients with DM1, whether they are children, adolescents or adults," Alan Rubino, the executive chair at AMO Pharma, said in a statement.1 "We are now focused on progressing a new clinical study in adults with adult-onset DM1. We are very grateful to the FDA and to the patients, families, clinicians and investors who have supported our research thus far and we look forward to working with the community to advance this program as rapidly as possible. We will make an announcement regarding the start date and site locations for the adult onset DM1 study shortly."

In September 2023, data from REACH-CDM showed that AMO-02 failed to meet its primary end point; however, achieved clinically and statistically significant benefit in various functional and objective assessments.2 The study featured 56 patients across sites in the US, Canada, Australia, and New Zealand who received 1000 mg of AMO-02 once daily for 52 weeks, with an optional further 32-week extended access period. After a year’s worth of treatment, the agent was unsuccessful in distinguishing itself from placebo on the primary end point of Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS), an 11-item rating scale assessing symptom severity of domains relevant to congenital myotonic dystrophy.

Despite this, treatment with the agent was associated with clinically significant improvements in cognitive performance, as assessed through Peabody Picture Vocabulary Test (P <.05), and improvement in the 10-meter walk/run test (P = .054). Treated patients also saw significant reductions in creatine phosphokinase, a widely used biomarker of skeletal and cardiac muscle integrity (P <.05). Notably, 98% of patients opted to continue treatment in the open-label extension (OLE), and 85% of patients opted to continue treatment at the conclusion of the 1-year OLE study.

Hanns Lochmuller, MD, PhD, FAAN, professor of neurology at University of Ottawa Faculty of Medicine

Hanns Lochmuller, MD, PhD, FAAN

Credit: University of Ottawa Faculty of Medicine

"The results of the REACH-CDM Study showed measures of efficacy benefit across multiple symptom areas, and we are very excited that this clinical development program will continue to move forward," investigator Hanns Lochmuller, MD, PhD, FAAN, professor of neurology at University of Ottawa Faculty of Medicine, said in a statement.1 "We remain very hopeful that this investigational therapy can have a transformative impact on the health of patients living with this ultra-rare, severe muscular dystrophy in the years ahead."

In the study, a composite statistical analysis of outcomes assessing motor skills, muscle strength, cognitive ability, daily living skills, and biomarker data revealed statistically significant benefits through treatment with AMO-02 vs placebo (P <.05). Of note, the benefits and clinical improvement seen in treated patients were correlated with pharmacokinetic parameters that showed increasing plasma levels of AMO-02. Overall, more participants showed a positive response following AMO-02 treatment than placebo on 10 of the 12 quantifiable measures.

Following announcement of the results, Mike Snape, PhD, chief scientific officer of AMO Pharma, sat down in an interview with NeurologyLive® to discuss how AMO-02 works to address the underlying causes of congenital myotonic dystrophy. He also talked about the key safety findings from the clinical trial, and how the therapy differentiated itself from placebo. Additionally, Snape spoke about why the rating scale instruments used were challenging to interpret when assessing the therapy's efficacy, along with other tests that provided evidence of its effectiveness.

AMO-02, otherwise known as tideglusib, is also in development for other conditions such as adult-onset myotonic dystrophy and other central nervous system, neuromuscular indications. In cellular and animal models of congenital myotonic dystrophy as well as in muscle biopsies from patients, activity of glycogen synthase kinase 3 beta (GSKß) has been shown to increase. AMO-02 is an inhibitor that has demonstrated an ability to normalize levels of GSK3ß in transgenic models and in ex vivo tissue samples in patients with congenital myotonic dystrophy.

In 2020, a phase 2 study (NCT02858908) of AMO-02 in congenital and childhood-onset myotonic dystrophy type 1 was published in Pediatric Neurology. The trial featured 16 participants aged 13 to 34 years who received 12 weeks of single-blind fixed-dose oral treatment with either 400 mg (n = 8) or 1000 mg (n = 8) of AMO-02. At the conclusion of the analysis, findings showed that AMO-02 plasma concentrations conformed to a 2-comparment model with first-order absorption and elimination, along with dose-dependent increases in exposure were observed.3

The therapy showed a safe and tolerable profile, with no discontinuations because of adverse events or dose adjustments. After 12 weeks of treatment, a majority of treated patients showed improvement in their central nervous system and neuromuscular symptoms relative to placebo baseline, with a larger response noted in the 1000 mg/day group. AMO-02 exposure was significantly correlated with change from baseline on several key efficacy assessments.

1. AMO Pharma Completes Meeting with U.S. FDA and Outlines Plans to Advance Clinical Development of AMO-02 (tideglusib) in Treatment of Myotonic Dystrophy. News Release. AMO Pharma. Published May 2, 2024. Accessed May 3, 2024.
2. AMO Pharma announces affirming data from REACH-CDM clinical trial for AMO-02 in treatment of myotonic dystrophy. News release. AMO Pharma. September 6, 2023. Accessed May 3, 2024.
3. Horrigan J, Gomes TB, Snape M, et al. A phase 2 study of AMO-02 (Tideglusib) in congenital and childhood-onset myotonic dystrophy type 1 (DM1). Pediatr Neurol. 2020;112:84-93. doi:10.1016/j.pediatr.neurol.2020.08.001.
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