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BOSTON, July 17, 2025 – The Institute for Clinical and Economic Review (ICER) today posted its revised Evidence Report assessing the comparative clinical effectiveness of nusinersen (Spinraza®, Biogen), onasemnogene abeparvovec-xioi (Zolgensma®, Novartis), and risdiplam (Evrysdi®, Genentech) for spinal muscular atrophy (SMA). ICER is also assessing the comparative clinical effectiveness and value of apitegromab (Scholar Rock Holdings) for SMA.
“SMA, in its most common forms, has been a devastating degenerative neurologic disease of infants and children,” said ICER’s Chief Medical Officer, David Rind, MD. “Disease modifying therapies and newborn screening have dramatically altered the course of disease and represent one of the great medical success stories in the past decade. However, we still have important uncertainties about how best to utilize these therapies to provide maximal benefits to those affected.”
This Evidence Report will be reviewed at a virtual public meeting of the Midwest CEPAC on August 1, 2025. The Midwest CEPAC is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.
Register here to watch the live webcast of the virtual meeting.
A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report reflects changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.
Key Clinical Findings
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Apitegromab: the net health benefit is based on one unpublished study. In this population, ICER judged that treatment with apitegromab likely provides comparable or incremental benefits compared with no additional therapy, but that there is some possibility of substantial benefit with long-term use as well as some possibility of net harm. ICER rated the current evidence for apitegromab as promising but inconclusive (“P/I”) for that study population. There are insufficient data (“I”) to estimate the net health benefits of apitegromab in other populations.
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Nusinersen: The evidence indicates that, after treatment with onasemnogene abeparvovec, treatment with nusinersen did not result in any identifiable new harms. Repeated spinal cord injections (specifically intrathecal injections), however, are burdensome and have rare but serious potential adverse events. Given the substantial uncertainty, ICER judged that there is moderate certainty of comparable to substantial net benefit, with a small, but possible net harm from repeated intrathecal injections compared with no additional therapy. Therefore, ICER rated the evidence as promising but inconclusive (“P/I”).
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Risdiplam: The evidence indicates that, after treatment with onasemnogene abeparvovec, treatment with risdiplam resulted in some improvements in swallowing and breathing function. The safety profile was consistent with risdiplam’s known adverse events (e.g., rash, constipation). The gains are potentially substantial and there do not appear to be important harms, but there is substantial uncertainty about the magnitude of the net benefits. ICER judged that there is moderate certainty of a comparable, small, or substantial net health benefit compared with no additional therapy, or comparable or better (C++).
There are no head-to-head trials comparing risdiplam, nusinersen, and onasemnogene abeparvovec to each other as first-line therapy in patients with SMA of any type. Given the lack of comparative data, we conclude that there is insufficient (“I”) data to estimate the net health benefits of risdiplam, nusinersen, and onasemnogene abeparvovec compared to one another in patients with SMA of any type or age.
Key Cost-Effectiveness Findings
ICER evaluated the cost-effectiveness of apitegromab only because it will most likely be used as an add-on therapy to nusinersen or risdiplam. Apitegromab has not yet been approved by the FDA for SMA, and the manufacturers have not yet announced a US price for the therapy if approved.
ICER has calculated a health benefit price benchmark (HBPB) to be between $4,600 and $30,200 per year.
ICER’s HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, net of all rebates and discounts, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.
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