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Results from the phase 3 SAPPHIRE trial show significant improvements in motor function in children and adults with spinal muscular atrophy.
New results from the double-blind, randomized, placebo-controlled phase 3 SAPPHIRE trial (NCT05156320) demonstrate the robust effectiveness of apitegromab at improving motor function—as measured by the Hammersmith Functional Motor Scale Expanded (HFMSE)—in children and adults with spinal muscular atrophy (SMA), according to data published by investigators in The Lancet Neurology and a news release from Scholar Rock.1-3
Spinal muscular atrophy impacts motor neuron function. | Image Credit: © Julian - stock.adobe.com
Importantly, apitegromab—an investigational, fully human monoclonal antibody—was safe and well-tolerated across all age groups, and no novel safety findings were observed.1,2
“The robust apitegromab data reinforce that effective SMA treatment regimens should address both motor neuron preservation and muscle function,” Akshay Vaishnaw, MD, PhD, president of R&D at Scholar Rock, said in the news release.1
The SAPPHIRE trial aimed to fill critical gaps in SMA treatments. Despite the availability of new drugs that have reduced the burden of SMA and improved outcomes, there remains a major unmet need for therapies that can directly manage the progressive muscle weakness sustained with SMA. In late 2024, Scholar Rock announced topline results from SAPPHIRE, highlighting the meeting of the trial’s primary end point as patients with SMA treated with apitegromab had statistically significant improvements versus placebo in motor function.1,4
Trial Name: Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam (SAPPHIRE)
ClinicalTrials.gov Identifier: NCT05156320
Sponsor: Scholar Rock, Inc.
Completion Date: December 18, 2024
With these comprehensive, newly published results, specific insights can be made into apitegromab’s efficacy and safety. Over 52 weeks, the trial enrolled 188 patients aged between 2 and 21 years with SMA who were receiving survival motor neuron (SMN)-targeted treatment to receive either apitegromab in doses of 10 mg/kg or 20 mg/kg, or a placebo. One hundred and twenty-eight patients were administered apitegromab, while 60 patients received a placebo.1,2
At the 12-month follow-up point, investigators observed a least squares mean difference in HFMSE change from baseline of 1.8 points (95% CI, 0.30–3.32; P = .019) for individuals aged 2 through 12 years receiving either dose of apitegromab compared with placebo. Specifically, there was a difference of 1.4 points in HFMSE score for apitegromab 20 mg/kg versus placebo (95% CI, 0.34–3.13; P = .11), indicating that a higher dose of apitegromab achieves comparable levels of efficacy to the overall patient population that received either a 10- or 20-mg/kg dose.1,2
Emphatic improvements were observed across pre-specified patient subgroups, including patient age, their geographic region, their age at SMN-targeted treatment initiation, and the type of SMN-targeted treatment. These data are key, as they would allow pharmacists and other health care providers to freely prescribe the medication to most patients, regardless of the type of SMN-targeting therapy they may be using.1,2
A series of secondary end points were measured on patients aged 2 through 12 receiving apitegromab or placebo, for which multiple improvements were observed. There were 30.4% of patients receiving apitegromab that had a 3-point-or-more improvement in HFMSE, versus 12.5% of patients on placebo. Furthermore, 19.6% of patients receiving apitegromab had a 4-point or more improvement in HFSME versus 6.3% of patients on placebo at 52 weeks.1,2
Apitegromab has gained multiple FDA designations on its path towards a possible approval, including fast track, orphan drug, and rare pediatric disease designations. Earlier this year, Scholar Rock submitted a biologics license application to the FDA as a muscle-targeted therapy for motor function improvement in patients with SMA. With a target action date of September 22, 2025, pharmacists and health care professionals should be vigilant regarding apitegromab’s future and a potential approval.1,5
With apitegromab, pharmacists are poised to play an integral role in patient dosing and counseling. Already essential in helping manage a patient’s muscle wasting and motor function decline over time, pharmacists would be able to lead in the complex process of acquiring apitegromab for patients, helping to navigate insurance coverage and prior authorizations. Families of patients with SMA also could be counseled by pharmacists on how apitegromab acts in the body, how it is administered, and possible adverse effects of the treatment.
“To improve outcomes and support activities like breathing, eating, swallowing, standing, and walking, which require muscle strength and motor function, a comprehensive approach targeting both components of the disease is critical,” Vaishnaw continued. “The SAPPHIRE findings support the value of muscle-targeted therapies for children and adults living with SMA.”1
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