First Therapy to Target Muscle Loss in Spinal Muscular Atrophy Gets FDA Approval

The FDA approved apitegromab (Isembyld) injection to treat spinal muscular atrophy (SMA) in adults and pediatric patients ages 2 years and older who currently are receiving an SMN2-targeted treatment, the agency announced Friday.

The drug is the first therapy approved for SMA that directly targets muscle loss, the FDA said.

SMA affects approximately one in 10,000 live births and is among the leading genetic causes of infant mortality. It is caused by reduced levels of the SMN protein due to deletions or mutations in the SMN1 gene. A nearly identical gene, SMN2, produces low levels of functional SMN protein. Several treatments approved for SMA, including risdiplam (Evrysdi) and nusinersen (Spinraza), work by correcting this defect to produce more of the missing protein.

“While these treatments have significantly improved outcomes for many patients, those with more advanced disease continue to experience substantial motor limitations (including the ability to walk or move independently), highlighting the need for therapies that directly address muscle loss,” the FDA stated.

Apitegromab’s safety and effectiveness were evaluated in the 52-week double-blind, phase III SAPPHIRE trial; the findings were published this month in Lancet Neurology. SAPPHIRE participants were ages 2 to 21 years and had genetically documented non-ambulatory type 2 or type 3 SMA, an estimated life expectancy greater than 2 years, motor function scores of 10 to 45 points on the Hammersmith Functional Motor Scale-Expanded, and received nusinersen for at least 10 months or risdiplam for at least 6 months at screening.

Patients were randomly assigned to receive apitegromab 10 mg/kg or 20 mg/kg or placebo once every 4 weeks for approximately 1 year. The primary analysis, conducted in 156 patients ages 2 to 12 years, showed that participants receiving apitegromab 10 mg/kg had improvement in motor function scores at 1 year while those on placebo declined. Those in the treatment arm were more than twice as likely than patients in the placebo arm to demonstrate a clinically meaningful improvement (34.2% vs 13.5%).

The incidence and severity of adverse events were similar between apitegromab and placebo, and consistent with SMA and background SMA therapy. The most common adverse reactions were upper respiratory tract infections, vomiting, cough, other viral infections, headache, gastroenteritis, and pharyngitis. An increased risk of fractures, including serious fractures, occurred in patients treated with apitegromab. The drug may cause fetal harm and may affect reproductive function, the FDA cautioned.

Findings from the phase II TOPAZ trial also indicated support for apitegromab.

According to the drug’s prescribing information, the recommended dosage of apitegromab is 10 mg/kg administered once every 4 weeks as an intravenous infusion over approximately 60 to 120 minutes, at an infusion rate no greater than 150 mL/hour. Drugmaker Scholar Rock said apitegromab will be available to ship in the coming days.