Researchers from the Wake Forest School of Medicine in Winston-Salem, South Carolina announced study results which found the combination therapy of onasemnogene (Zolgensma®) and risdiplam (EvrysdiTM) was well-tolerated in 4 patients with spinal muscular atrophy (SMA) type 1.

The authors of the small case study, published in Muscle & Nerve, also stated “all patients experienced objective and subjective improvement” with the combination treatment.

The patients began taking daily risdiplam after having reached a perceived plateau in therapeutic benefits from an onasemnogene infusion. Two of the 4 patients experienced fatigue and weakness after beginning risdiplam treatment but these effects resolved during the first month. A few weeks following initiation of risdiplam, 1 patient did experience hospitalization for SARS CoV-2 and subsequent post-viral pneumonia. No other adverse events related to the combination therapy were reported during the trial.

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Based on these results, the authors stated that the combination therapy was well-tolerated by patients but that larger prospective trials need to be performed to identify potentially rare adverse events and to test the efficacy of the treatment combination compared to each therapy alone.

Onasemnogene was approved by the US Food and Drug Administration (FDA) in 2019 as the second disease-modifying treatment and first gene therapy for SMA. It is given as a single intravenous infusion for patients under 2 years old. The gene therapy utilizes an adeno-associated virus, serotype 9 (AAV9) vector to provide a working copy of an SMN gene, which is deficient in patients with SMA.

Risdiplam was approved in 2020 as the third disease-modifying treatment but first oral therapy for SMA. It is administered daily and is indicated for patients 2 months and older. The treatment helps cells of the body produce functional SMN proteins from the SMN2 gene, which are normally unstable due to a lack of inclusion of exon 7.


Oechsel KF, Cartwright MS. Combination therapy with onasemnogene and risdiplam in spinal muscular atrophy type 1. Muscle Nerve. Published online July 20, 2021. doi:10.1002/mus.27375