EXPANDING THE THERAPEUTIC LANDSCAPE OF SMA:  SAFETY AND EFFICIENCY OF APITEGROMAB

Urszula Gadomska; Mikołaj Daniluk; Natalia Dejewska; Jowita Wiktoria Maksymiuk; Zuzanna Walewska; Mateusz Onopiuk; Zuzanna Szumska; Szymon Klimaszewski; Jonasz Żuk; Kinga Bukała

doi:10.31435/ijitss.2(50).2026.5976

Authors

Urszula Gadomska Bielański Hospital named after Rev. Jerzy Popiełuszko, Warsaw, Poland https://orcid.org/0009-0005-8381-9955
Mikołaj Daniluk Independent Public Central Clinical Hospital in Warsaw, Poland https://orcid.org/0009-0005-6458-373X
Natalia Dejewska Bielański Hospital named after Rev. Jerzy Popiełuszko, Warsaw, Poland https://orcid.org/0009-0006-4806-6780
Jowita Wiktoria Maksymiuk Bielański Hospital named after Rev. Jerzy Popiełuszko, Warsaw, Poland https://orcid.org/0009-0004-3130-9913
Zuzanna Walewska Bielański Hospital named after Rev. Jerzy Popiełuszko, Warsaw, Poland https://orcid.org/0009-0001-0088-4294
Mateusz Onopiuk Bielański Hospital named after Rev. Jerzy Popiełuszko, Warsaw, Poland https://orcid.org/0009-0003-9916-1292
Zuzanna Szumska District Health Center Ltd. in Otwock, Poland https://orcid.org/0009-0009-5287-9946
Szymon Klimaszewski Szymon Klimaszewski praktyka lekarska dentystyczna, Gdansk, Poland https://orcid.org/0009-0001-3505-2797
Jonasz Żuk Independent Public Central Clinical Hospital in Warsaw, Poland https://orcid.org/0009-0001-7500-7982
Kinga Bukała Medical University of Lodz, Lodz, Poland https://orcid.org/0009-0003-9587-4826

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5976

Keywords:

Apitegromab, Spinal Muscular Atrophy, Myostatin Inhibitor, Myostatin

Abstract

Spinal muscular atrophy (SMA) is a genetic disease caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, leading to a deficiency of the SMN protein and progressive degradation of motor neurons and muscle atrophy.

Currently, three therapies are available that increase SMN protein levels: nusinersen, risdiplam, and onasemnogene abeparvovec; however, many patients still struggle with persistent motor function deficits. For this reason, an additional form of treatment is needed.

The myostatin inhibitor apitegromab is a fully human monoclonal antibody that selectively inhibits the activation of promyostatin and the latent form of myostatin, thereby preventing the release of active myostatin, a negative regulator of muscle growth.

The Phase 2 TOPAZ trial demonstrated that apitegromab led to considerable improvements in motor function over 12 months, particularly in younger, nonambulatory patients, where the 20 mg/kg dose resulted in a mean increase in the Hammersmith Functional Motor Scale Expanded (HFMSE) of 7.1 points.

Long-term analysis after 36 months from the TOPAZ OLE Study confirmed the durability of these benefits, with nonambulatory patients showing a mean increase of 4.0 points in HFMSE and 2.4 points in RULM. The pivotal phase 3 SAPPHIRE study provided evidence of apitegromab's efficacy. In children aged 2-12 years, a statistically significant improvement of 1.8 points on the HFMSE scale was achieved (p=0.019). In all studies, apitegromab was well tolerated and demonstrated a favorable safety profile. These results show that apitegromab is an effective adjunctive therapy in SMA.

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