Disease-modifying treatments for patients with spinal muscular atrophy (SMA) that directly target the deficiency of survival of motor neuron (SMN) protein have been approved in over 50 countries. While these treatments have positively impacted the disease trajectory, treated patients may continue to experience motor deficiencies.
Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral SMN2 pre-mRNA splicing modifier that has been approved by the FDA for the treatment of patients with SMA, aged 2 months and older. GYM329 is an investigational, recycling and antigen-sweeping monoclonal anti-myostatin antibody (myostatin is a negative regulator of skeletal muscle growth).
MANATEE (NCT05115110) is a multicenter, two-part, randomized, placebo-controlled, double-blind study that will investigate the effect of GYM329 in combination with risdiplam in treatment-naïve and non-treatment-naïve ambulant patients, aged 2–10 years at screening. Part 1 (target enrollment N~36) will assess safety, tolerability and pharmacokinetics/pharmacodynamics of different GYM329 doses in combination with risdiplam. Part 2 (target enrollment N~144) will assess efficacy and safety of the Part 1-selected dose of GYM329 in combination with risdiplam.
MANATEE aims to assess the safety, tolerability and pharmacokinetics/pharmacodynamics of GYM329 in combination with risdiplam in patients with SMA.
Risdiplam has demonstrated clinically meaningful benefit in patients with SMA and there have been no treatment-related safety findings leading to treatment withdrawal in the risdiplam studies to date. In a mouse model of SMA, the combination of RO7204239 and an SMN2 splicing modifier was found to further improve muscle size and strength compared with treatment with SMN2 splicing modifier treatment alone. This approach may lead to a complementary effect on improvement of patients’ motor function. Here, we present the design of the MANATEE study.
This study will provide valuable information about safety and efficacy of GYM329 in combination with risdiplam treatment in ambulant pediatric patients with SMA.