Pediatric Phase 2/3 Trial to Test Anti-myostatin Antibody with Evrysdi

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by Patricia Inacio PhD |

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Evrysdi | SMA News Today | Illustration of medicine bottle labelled clinical trials

Roche and its subsidiary Genentech are launching a Phase 2/3 clinical trial to evaluate the safety and efficacy of GYM329 (RO7204239), an investigational anti-myostatin antibody, in combination with Evrysdi (risdiplam) in children with spinal muscular atrophy (SMA).

The MANATEE trial has two parts. In part one, 36 patients, age 2 to 10, will be tested to determine the best dose of GYM329 for further testing. This part of the trial will take place at approximately 15 clinical sites in the U.S., Belgium, Germany, Italy, Poland, the Netherlands and the U.K., according to a press release from Spinal Muscular Atrophy U.K.

In part two, around 144 patients will be randomly assigned to a placebo or GYM329, at the previously determined dose, administered subcutaneously (under the skin) every four weeks. All patients will receive a daily dose of Evrysdi.

The study is open to patients who are treatment-naïve (have never been treated) or who were previously treated with Evrysdi, Spinraza (marketed by Biogen), or Zolgensma (marketed by Novartis), and who can walk independently, among other still-undisclosed criteria.

Enrolment for part one is expected to start in February 2022, while part 2 may start by the end of 2023. Patients interested in joining the trial should discuss it with their physicians. More information on enrolment criteria will be available on Roche’s ForPatients site in the coming weeks.

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Looking ahead for SMA

Muscle and Combo Therapies Likely Next Focus for SMA, Experts Say

SMA is caused by low to no levels of SMN, a protein essential for motor neuron and muscle health, due to mutations in the SMN1 gene. A “backup” gene, SMN2, is capable of producing SMN. However, a slight difference in its DNA sequence limits the amount of functional SMN it produces to 10%–15%.

Currently approved therapies for SMA, including Evrysdi, work by increasing the production of a functional SMN protein.

Specifically, Evrysdi acts through the SMN2 gene to boost the production of working SMN protein, which is impaired in SMA. These are known as SMN-targeted therapies.

Myostatin is a protein found naturally in the muscles where it works to prevent overgrowth of skeletal muscles, those used for voluntary movement. In preclinical as well as human clinical studies, inhibition of myostatin led to a significant increase in muscle mass.

The combination of therapies with different modes of action may boost the motor function and outcomes of children with SMA.

Roche intends to assess the combination therapy in other groups of SMA patients, including those unable to walk without assistance, and across a broader age range.