Enrollment complete in Phase 3 trial of taldefgrobep alfa for SMA
Biohaven to test muscle targeting therapy at 58 sites in US, Europe
Biohaven Pharmaceuticals has completed the enrollment of children and young adults with spinal muscular atrophy (SMA) in a pivotal Phase 3 trial in the U.S. and Europe that is testing its experimental muscle-targeting therapy taldefgrobep alfa.
The company had expected to recruit about 180 patients of all SMA types for RESILIENT (NCT05337553), slated to run across 58 study sites spanning the U.S., and in Belgium, Czechia, Italy, the U.K. and several other European nations.
The Phase 3 trial will be testing how safe taldefgrobep alfa is against a placebo and how effective it is at ameliorating motor function when used as an add-on to standard SMA disease-modifying therapies.
“We are thrilled to complete enrollment in this pivotal trial for SMA as it brings us one step closer to advancing a novel muscle targeting therapy for patients with SMA,” Lindsey Lair, MD, Biohaven’s vice president and clinical development lead for the SMA program, said in a company press release.
RESILIENT recruited 180 patients with all SMA types
SMA is a genetic disease that causes motor neurons — the nerve cells that control muscle movement — to gradually degenerate and die. This results in muscle weakness and wasting, which worsen over time, leading to problems with breathing, eating, and walking.
While three disease-modifying therapies are available for SMA, none of them can reverse the damage that has already occurred, meaning that many patients will continue to experience weakness and impairments in quality of life.
“While we have had good progress with current therapies, a high unmet need for safe and effective supportive treatments for SMA remains, as many patients still experience significant weakness and reduced levels of functioning,” said Kenneth Hobby, president of Cure SMA, a patient advocacy group.
Myostatin is a naturally occurring protein that normally signals muscles to stop growing, preventing them from becoming too large during development. In SMA, however, myostatin can limit the muscle growth that’s needed for patients to reach important motor milestones.
Taldefgrobep alfa is designed to block myostatin’s activity in two ways: by directly lowering myostatin’s levels and by blocking its protein receptor, which stops myostatin-derived signals. The expected result, according to Biohaven, is increased muscle mass and strength.
Despite recent advances in SMA genetic treatments, patients still experience weakness and impairments in quality of life that can be alleviated by enhancing muscle mass and function, on top of what is delivered by current standard of care treatments.
The RESILIENT study includes patients, ages 4 to 21, who have a confirmed diagnosis of SMA and are on a stable dose of Spinraza (nusinersen) or Evrysdi (risdiplam), or have taken a single dose of Zolgensma (onasemnogene abeparvovec-xioi). All three are approved treatments for SMA.
Patients will be randomly assigned to receive either taldefgrobep alfa or a placebo, which will be administered via a subcutaneous or under-the-skin injection once weekly for 48 weeks, or about 11 months.
The study’s main goal is to see if taldefgrobep alfa is able to improve motor function when compared with the placebo. Its efficacy will be determined by evaluating changes from the study’s start to week 48 in the 32-item Motor Function Measure (MFM-32) total score.
“Despite recent advances in SMA genetic treatments, patients still experience weakness and impairments in quality of life that can be alleviated by enhancing muscle mass and function, on top of what is delivered by current standard of care treatments,” Lair said.
After the 48 weeks of the study, patients will have the option to roll over into an open-label extension in which they will receive treatment with taldefgrobep alfa for an additional period of 48 weeks.
The U.S. Food and Drug Administration has given taldefgrobep alfa fast track and orphan drug designations for the treatment of SMA. The experimental therapy also has been named an orphan drug in Europe.