SMA Patients on Apitegromab Still Showing Benefits at Three-Year Mark

A three-year follow-up study of apitegromab, an investigational drug for spinal muscular atrophy (SMA), continued to show patient benefits that were reported at the study’s one-year mark, with no new safety issues.

The phase II TOPAZ study followed 35 non-ambulatory patients with SMA types 2 or 3 who received apitegromab for 36 months. Patients ranged from 2- to 19-years-old, with a mean age of 7.3 years.

At the three-year assessment of those still taking the drug, 88% of patients had maintained or improved motor milestones that they had achieved at baseline. Some patients, those who had received the disease-modifying therapy Spinraza (nusinersen) before turning 5 years old, had gained new motor milestones, and two patients were able to walk independently.

Apitegromab works by inhibiting myostatin, a protein that negatively regulates muscle growth. While medicines like Spinraza, Evrysdi (risdiplam) and one-time gene replacement therapy Zolgensma (onasemnogene abeparvovec-xioi) have transformed the treatment landscape, allowing patients treated as newborns to achieve normal motor milestones, these medicines don’t improve muscle atrophy and weakness that occurred before receiving the therapy.

Many patients around the world don’t have access to these disease-modifying medicines, or receive them years later, after they have sustained muscle weakness and motor neuron damage. Apitegromab is being developed as a potential complementary therapy to these other treatments to help maintain or potentially improve motor milestones.

“There are many individuals with SMA treated after the onset of symptoms who manifest persistent denervation atrophy and weakness,” the study authors wrote. “These individuals have a range of impaired motor function with substantial unmet medical need. A treatment that increases the functional capacity of intact muscle fibers within partially denervated muscle may address this unmet medical need.”

These results follow earlier reporting from 2021 showing positive outcomes for patients after 12 months. The safety profile remained consistent with earlier results, with no new safety concerns identified. The most common side effects were fever, nasopharyngitis, COVID-19 infection, vomiting and upper respiratory tract infection. A phase III trial called SAPPHIRE is currently ongoing to further assess the drug's efficacy and safety.

This study, “Long-term efficacy, safety, and patient-reported outcomes of apitegromab in patients with spinal muscular atrophy: results from the 36-month TOPAZ study,” was published in Frontiers in Neurology in July 2024.