The effect of the antilatent myostatin sweeping antibody GYM329 in combination with risdiplam in ambulant pediatric patients with a form of spinal muscular atrophy (SMA) will be investigated in a clinical trial.

“The aim of combining risdiplam and GYM329 is to target the underlying cause of SMA by increasing levels of functional SMN protein while also supporting muscle growth,” the authors of the study explained.

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As presented in a poster at the 2022 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, the 2-part, multicenter, randomized, placebo-controlled, double-blind MANATEE study (NCT05115110) will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of the combined therapy.

The study will enroll treatment-naïve and non-treatment-naïve ambulant pediatric patients (aged 2 to 10 years at screening) with a genetic diagnosis of 5q-autosomal recessive SMA who are symptomatic and have not used antimyostatin therapies.

Part 1 (target enrollment n≈36) will consist of 4 main phases: (1) an 8-week risdiplam run-in treatment phase, (2) a 24-week double-blind treatment phase in which participants will be divided into cohorts to receive different GYM329 doses in combination with risdiplam, (3) a 72-week open-label treatment phase, and (4) a 2-year open-label extension phase. The primary objective is to determine the appropriate dose of GYM329 for part 2 of the study.

Part 2 (target enrollment n≈144) will consist of 3 main phases: (1) an 8-week risdiplam run-in treatment phase, 2) a 72-week double-blind treatment phase in which participants will be randomized (1:1) to receive either GYM329 and risdiplam or placebo and risdiplam, and (3) a 2-year open-label extension phase.

Key outcomes include changes from baseline in the revised Hammersmith scale, motor function measure scores, lean muscle mass, and safety.

GYM329 specifically binds the inactive form of myostatin and reduces the amount converted into active myostatin.

References

Duong T, Darras BT, Morrow J, et al. MANATEE: a study of GYM329 (RO7204239) in combination with risdiplam treatment in pediatric patients with SMA. Poster presented at: 2022 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference; March 13-16, 2022; Nashville, TN.

A study to investigate the safety and efficacy of RO7204239 in combination with risdiplam (RO7034067) in ambulatory children with spinal muscular atrophy. ClinicalTrials.gov. November 10, 2021. Updated February 18, 2022. Accessed March 15, 2022.