FDA Approves First Muscle-Targeting Therapy for Spinal Muscular Atrophy
Federal regulators have granted approval to a new injection designed to combat muscle loss in individuals living with spinal muscular atrophy (SMA). Announced by the U.S. Food and Drug Administration (FDA), the newly approved medication, known as apitegromab and marketed under the brand name Isembyld, is indicated for adult and pediatric patients ages two years and older. Crucially, the treatment is intended for patients who are already receiving an existing SMN2-targeted therapy, marking a significant milestone as the first approved SMA treatment to directly address muscle deterioration rather than the underlying genetic defect alone.
Spal muscular atrophy is a rare genetic condition impacting roughly one in every 10,000 live births, and it remains a leading genetic cause of infant mortality. The disorder stems from reduced levels of the survival motor neuron (SMN) protein, which is caused by deletions or mutations within the SMN1 gene. Although a nearly identical backup gene called SMN2 produces low quantities of functional protein, it is generally insufficient to prevent disease progression. Several established therapies, such as nusinersen and risdiplam, focus on modifying this genetic deficit to generate more of the missing protein.
While these genetic-targeting drugs have dramatically improved outcomes for many patients, the FDA noted that individuals with more advanced forms of the disease continue to experience substantial motor limitations. These include challenges with walking and moving independently, creating an urgent clinical need for therapies that directly protect and support muscle tissue. Apitegromab is designed to fill this gap by acting directly on the muscles.
The safety and efficacy of apitegromab were evaluated during the 52-week, double-blind, phase III SAPPHIRE trial, the findings of which were published in Lancet Neurology. The study enrolled participants aged two to 21 years who had documented non-ambulatory type 2 or type 3 SMA, an estimated life expectancy of greater than two years, and specific motor function scores on the Hammersmith Functional Motor Scale-Expanded. Additionally, participants had been receiving stable doses of nusinersen for at least 10 months or risdiplam for at least six months prior to screening. Patients were randomly assigned to receive either a 10 mg/kg dose of apitegromab, a 20 mg/kg dose, or a placebo administered intravenously once every four weeks for approximately one year.
According to the primary analysis involving 156 patients aged two to 12 years, participants who received the 10 mg/kg dose of apitegromab demonstrated noticeable improvements in motor function scores after one year, whereas those in the placebo group experienced a functional decline. Furthermore, patients in the treatment arm were more than twice as likely to achieve a clinically meaningful improvement compared to the placebo group, with response rates of 34.2% versus 13.5%, respectively.
Regarding safety, the incidence and severity of adverse events were comparable between the apitegromab and placebo groups, remaining consistent with the profile of SMA and background therapies. Commonly reported adverse reactions included upper respiratory tract infections, vomiting, cough, viral infections, headache, gastroenteritis, and pharyngitis. However, the FDA highlighted an increased risk of bone fractures, including serious fractures, among patients treated with the drug. Regulatory warnings also caution that the therapy may cause fetal harm and could potentially impact reproductive function.
The approval is further supported by findings from the earlier phase II TOPAZ trial. According to the drug’s prescribing information, the recommended dosage is 10 mg/kg given as an intravenous infusion over 60 to 120 minutes every four weeks, at a rate not exceeding 150 mL/hour. Drug manufacturer Scholar Rock announced that the medication will be distributed to patients in the upcoming days.
Source: MedPage Today
