As part of its Q2 2024 Financial Results and Business Progress reporting, Scholar Rock disclosed new positive data from its Phase II TOPAZ trial, with results showing continued and sustained motor function over four years in non-ambulatory patients with spinal muscular atrophy (SMA) treated with apitegromab and nusinersen. The positive data lays the foundation for apitegromab’s potential as the first myostatin inhibitor to gain approval as an adjunctive therapy in patients with SMA, according to GlobalData, a leading data and analytics company.
Apitegromab is one of three myostatin inhibitors currently in late-stage development as an adjunctive therapy to approved disease-modifying treatments to improve motor function in SMA patients. Apitegromab is a monoclonal antibody that is suggested to improve muscle strength by inhibiting myostatin activation through the selective binding of myostatin in skeletal muscle.
Christie Wong, Managing Neurology Analyst at GlobalData, comments: “Key opinion leaders (KOLs) previously interviewed by GlobalData highlighted that despite the availability of disease-modifying therapies such as Biogen’s Spinraza (nusinersen) and Roche’s Evrysdi (risdiplam), and gene transfer therapy Novartis’ Zolgensma (onasemnogene abeparvovec), there remains a significant disease burden for SMA patients who continue to have chronic motor impairments and functional deficits. As such, the prospect of adjunctive therapy that could improve muscle strength and mobility in SMA patients will be welcomed among physicians and SMA patients.”
In the TOPAZ trial, type II and type III SMA patients received an intravenous infusion of apitegromab every four weeks, in addition to the patients’ background treatment with an SMN-targeted therapy (nusinersen or risdiplam). Scholar Rock reported that there was a sustained motor function improvement from baseline when analyzed annually, from one year to four years of treatment.
At 48 months, a mean change of 5.3 points in the Hammersmith Functional Motor Scale (HFMSE) from baseline was observed in non-ambulatory patients aged 2-21, who received treatment with nusinersen combined with apitegromab. The mean change of HFMSE was greater for patients aged 2-12, at 6.4 points. In addition, the mean change in Revised Upper Limb Module (RULM) for patients aged 2-21 was 3.6 points and 6.4 points for patients aged 2-12 years.
Wong adds: “If positive results are achieved in Scholar Rock’s ongoing Phase III trials, SAPPHIRE and the open-label extension ONYX study, apitegromab could be the first myostatin inhibitor to be approved as an adjunctive therapy for SMA.”
However, KOLs noted that intravenous infusions are typically administered by professionals in a healthcare institution. As such, the route of administration of apitegromab could impair accessibility and compliance, particularly in non-ambulant patients.”
Apitegromab will compete with two other myostatin inhibitors also in Phase III development, Roche’s RG-6237 and Biohaven’s taldefgrobep alfa.
According to GlobalData’s latest report, “Spinal Muscular Atrophy: Seven Market Drug Forecast and Market Analysis”, myostatin inhibitors will contribute $259.4 million in sales to the SMA market across the 7MM* by 2033.
Wong concludes: “RG-6237 and taldefgrobep alfa are developed as subcutaneous injections, and if they can be administered at home by patients or their caregivers, they could offer greater convenience when compared to intravenous infusions.”
*7MM- US, France, Germany, Italy, Spain, UK, and Japan
