At the American Academy of Neurology (AAN) 2024 Annual Meeting, Biohaven presented its Phase III RESILIENT (NCT05337553) trial design, which investigates the efficacy and safety of taldefgrobep alfa in patients with spinal muscular atrophy (SMA). Taldefgrobep alfa is a myostatin inhibitor in development as an adjunctive therapy alongside marketed therapies to offer symptomatic relief to patients with type I–IV SMA. As taldefgrobep alfa is investigated in a large population of SMA patients, it could have a competitive edge against other myostatin inhibitors in late-stage development that are being investigated in subpopulations of SMA patients, says GlobalData, a leading data and analytics company.

Christie Wong, Pharma Analyst at GlobalData, comments: “The availability of disease-modifying therapies, Biogen’s Spinraza (nusinersen) and Roche’s Evrysdi (risdiplam), and curative gene therapy Novartis’ Zolgensma (onasemnogene abeparvovec), which increase the amount of SMN produced in the body, have greatly improved disease outcomes for SMA patients, allowing patients to reach normal childhood development milestones.”

However, presenters at AAN 2024 and key opinion leaders (KOLs) previously interviewed by GlobalData highlighted that while these SMN-dependent therapies have revolutionized SMA treatment and advanced the care of patients with SMA, many SMA patients continue to have chronic motor impairments and functional deficits. As such, there is a need for additional treatment options for patients with SMA.

The RESILIENT trial is a 48-week randomized, double-blind, placebo-controlled study of taldefgrobep alfa in SMA patients. Taldefgrobep alfa is proposed to both block active myostatin and inhibit activin receptor type IIB signaling in skeletal muscle and increase muscle mass. The trial enrollment includes both ambulant and non-ambulant patients aged 4–21 years with any SMA type on stable treatment of Spinraza or Evrysdi, and/or have a history of treatment with Zolgensma.

According to GlobalData’s Drug Database, there are two other myostatin inhibitors in Phase III development as adjunctive treatments for SMA. Scholar Rock’s apitegromab and Roche’s RG-6237/GYM329 are monoclonal antibodies against myostatin that are intended to be administered once per month via intravenous infusion and subcutaneous injection, respectively.

Wong continues: “The lower dosing frequency of apitegromab and RG-6237 could be convenient to patients and their caregivers, offering an advantage against taldefgrobep alfa’s once-weekly subcutaneous injection.”

However, the clinical trials for apitegromab and RG-6237 are restricted to specific SMA patient populations. Currently, apitegromab is being investigated in patients with SMA type II and type III on a stable treatment of Spinraza or Evrysdi, and/or with a history of treatment with Zolgensma. RG-6237 is investigated in type I-IV SMA patients on a stable dose of Evrysdi and/or with a history of treatment with Zolgensma.

Wong adds: “There is an opportunity for Scholar Rock to expand the eligible population for apitegromab by investigating its efficacy in patients with SMA type I and type IV. In addition, Roche may wish to consider investigating the efficacy of RG-6237 in patients on a stable treatment of Spinraza.

“While the first-to-market myostatin inhibitor will have its own accolades, factors such as the applicability across patient subtypes, dosing frequency, strong efficacy data, and long-term safety data could provide a competitive edge for the myostatin inhibitors, should they receive regulatory approval.”