Interim data from the STRONG clinical trial (NCT03381729), show early signs of efficacy of onasemnogene abeparvovec (Zolgensma; Novartis, East Hanover, NJ) in participants with spinal muscular atrophy (SMA) who are able to sit but not walk. Onasemnogene is an intravenously delivered gene therapy that addresses the genetic root cause of SMA approved for the treatment of SMA in individuals who are under age 2 years.
Children age 6 months to 5 years (n=30) who have Type 2 SMA (3 copies of the SMN2 allele) have been treated with 1 of 3 doses of onasemnogene. In 12 of 13 (92%) participants age 2 to 5 years, Hammersmith Functional Motor Scale-Expanded (HFMSE) scores increased a mean 11.7 points in 12 of 13 (92%) of participants age 2 to 5 years. This is compared to the natural history of SMA Type 2 in which the HFMSE score for this age group usually does not vary by more than 1 point over a 9-month period. A 3-point change is considered clinically meaningful and some studies suggest that to parent, a 1-point change is meaningful. No fatal treatment-emergent adverse events (TEAEs) occurred and 13 serious TEAEs occurred in 7 patients that included influenza, bronchitis, rhinovirus, respiratory tract infections, acute respiratory failure, asthma, transiently elevated liver enzymes, and elevated serum alakaline phosphatase.
In the STRONG study, participants age 6 months to 5 years with SMA who could sit but not stand or walk received a single intrathecally delivered dose of onasemnogene. Outcome measures include safety and tolerability, optimal dose, ability to stand unsupported for 3 or more seconds at age 6 to 24 months, and the change in Hammersmith Functional Motor Scale-Expanded (HFMSE) score from baseline to 12 months after receiving the dose.
These data were presented during the online presentation of the Muscular Dystrophy Association Clinical and Scientific Congress on March 24, 2020 in lieu of the annual meeting that was canceled due to the 2020 COVID-19 pandemic.
Vanessa Baute Penry, MD; Rachana Gandhi Mehta, MD; and Fatemeh Sadeghifar, BS
Brad Klein, MD, MBA, FAAN, FAHS, FAANEM, and Raissa Villanueva MD, MPH, FAAN
Michelle L. Dougherty, MD, FAES, FAAN