The FDA's Approval of High-Dose Nusinersen and the Future of Therapy in SMA: Thomas Crawford, MD

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“…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.”

On March 30, 2026, the FDA approved a new higher-dose formulation of nusinersen (Spinraza; Biogen) for spinal muscular atrophy (SMA). Following the approval, NeurologyLive® reached out to Thomas Crawford, MD, a pediatric neurologist at Johns Hopkins with more than 30 years of experience in SMA, to get his insight on the FDA’s decision, as well as the future of SMA care in general.

Crawford began by sharing his perspective on the FDA's approval of the higher-dose nusinersen (28 mg) regimen and providing context for the approval, noting that while the original 12-mg dose had demonstrated transformative efficacy—allowing infants who previously would have died to survive—the absence of safety concerns created a rationale for exploring whether a higher dose could yield additional benefit. Biogen's subsequent clinical program, though methodologically challenging given the already high bar set by the 12-mg regimen, ultimately demonstrated meaningful improvement with a 28-mg dose. Crawford emphasized that the safety profile between the 2 doses was comparable, and that the primary practical distinction involves the loading dose: the new protocol initiates with a single 50-mg dose, which carries a higher per-milligram cost requiring separate insurance authorization, before transitioning to the 28-mg maintenance regimen.

Regarding the broader treatment landscape, Crawford noted that all 3 currently approved disease-modifying therapies (DMTs) for SMA—nusinersen, onasemnogene abeparvovec-xioi (Zolgensma), and risdiplam (Evrysdi)— appear comparably effective, with treatment selection largely driven by practical considerations such as route of administration and tolerability rather than demonstrated efficacy differences. He highlighted bridging with risdiplam prior to definitive therapy as an emerging, though formally unstudied, practice that he views 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.