Thomas Crawford, MD, on High-Dose Nusinersen and the Future of SMA Treatment

This interview was originally published on our sister site, NeurologyLive®.

“…There's really no reason not to go forward with the 28 milligrams. It is the same price with 1 exception: the the new protocol starts with a single dose at 50 milligrams, as opposed to the continuous dose at 28… So the first loading dose is more expensive… No reason not to do it.”

The FDA approved an updated higher-dose formulation of the antisense oligonucleotide therapy nusinersen (Spinraza; Biogen) for spinal muscular atrophy (SMA) on March 30, 2026. In the wake of the decision, CGTLive®’s sister site NeurologyLive® spoke with Thomas Crawford, MD, a pediatric neurologist at Johns Hopkins with more than 3 decades of experience in SMA, to gather his perspective on the decision and the evolving landscape of SMA management.

Crawford opened by contextualizing the higher-dose nusinersen (28 mg) approval, explaining that although the original 12-mg regimen had already proven transformative—enabling survival in infants who previously would not have lived—the absence of meaningful safety concerns provided a reasonable basis for investigating whether dose escalation could produce further clinical gains. Biogen's subsequent development program faced a high methodological bar given the efficacy already established with the 12-mg dose, but ultimately yielded evidence of incremental benefit with the 28-mg regimen. Crawford pointed out that the safety profiles of the 2 doses are broadly comparable, and that the principal practical difference between them lies in the loading phase: the new protocol begins with a single 50-mg dose—which, due to its higher cost, requires a separate insurance authorization—before patients transition to the 28-mg maintenance dose.

Turning to the wider treatment landscape, Crawford observed that all 3 currently approved disease-modifying therapies (DMTs) for SMA—nusinersen, onasemnogene abeparvovec-xioi (Zolgensma), and risdiplam (Evrysdi)—appear to be comparably effective, and that treatment selection is driven more by practical factors such as route of administration and patient tolerability than by meaningful differences in efficacy. He also noted the growing, though formally unstudied, practice of bridging patients with risdiplam ahead of a definitive therapy decision—an approach he characterized as clinically reasonable.

Crawford also discussed pipeline developments and concluded by introducing "EVOLVE-SMA," a functional tiered classification system he is promoting to track population-level disease burden in the post-DMT era—a tool he proposes can be reliably self-reported by patients—as newborn screening and new treatment options increasingly shift SMA's clinical phenotype toward milder, longer-surviving presentations.