Biogen's High-Dose Nusinersen: Regulatory Hurdles and Market Potential in the SMA Landscape

The regulatory landscape for Biogen's high-dose nusinersen has taken a pivotal turn, with the U.S. Food and Drug Administration (FDA) issuing a Complete Response Letter (CRL) in September 2025. While the CRL requested additional technical data for the Chemistry, Manufacturing, and Controls (CMC) module of the supplemental New Drug Application (sNDA), it notably did not question the clinical efficacy or safety profile of the high-dose regimen Biogen Provides Regulatory Update on High Dose Regimen of Nusinersen^[1]. This distinction is critical: the DEVOTE study, which underpinned the application, demonstrated meaningful clinical benefits for spinal muscular atrophy (SMA) patients while maintaining a safety profile consistent with the approved 12 mg dose FDA and EMA Accept Applications for Higher Dose Regimen of Nusinersen^[2]. Biogen's prompt plan to resubmit the application underscores its confidence in the data and its commitment to expanding treatment options for a disease that has long demanded innovation.

The commercial stakes for Biogen are immense. The global SMA treatment market, valued at $1,636 million in 2024, is projected to grow at a compound annual growth rate (CAGR) of 3.60%, reaching $2,249.16 million by 2032 Nusinersen Market Research Report 2033^[3]. Nusinersen, marketed as Spinraza, has been a cornerstone of this market since its 2016 approval, but it now faces stiff competition from Novartis's gene therapy Zolgensma and Roche's oral therapy Evrysdi. Zolgensma, with its one-time administration and transformative efficacy for Type 1 SMA, commands a 49.2% market share in gene therapy segments Spinal Muscular Atrophy Market Size, Share, Report 2025-2033^[4]. However, its high cost and logistical challenges limit its reach, particularly in emerging markets. Evrysdi, meanwhile, offers convenience but has yet to match the long-term outcomes of antisense oligonucleotides like nusinersen.

Biogen's high-dose regimen could bridge this gap. By enhancing the therapeutic index of nusinersen—without compromising safety—it may appeal to clinicians seeking incremental improvements in motor function for Types 2 and 4 SMA. This is not merely a scientific proposition but a commercial one. The Asia-Pacific region, where healthcare infrastructure is rapidly improving and SMA awareness is rising, represents a $300 million growth opportunity by 2032 Global Nusinersen Market Size, Production, Price, Market Share, …^[5]. If Biogen secures regulatory approval in the U.S. and Europe by mid-2026, it could capture a significant share of this expansion, particularly as payers increasingly prioritize cost-effective, long-term therapies.

Yet challenges remain. The FDA's CRL highlights the importance of manufacturing robustness in biologics, a domain where Biogen has historically excelled. The company's partnership with Ionis Pharmaceuticals and manufacturing expertise may expedite resubmission, but delays could open the door for competitors. Additionally, the European Medicines Agency (EMA)'s ongoing review introduces regulatory uncertainty, though the harmonized data from the DEVOTE study suggests a favorable outcome.

For investors, the key question is whether Biogen can leverage its first-mover advantage in SMA to maintain market leadership. The high-dose nusinersen, if approved, would not only extend the drug's lifecycle but also reinforce Biogen's position in a therapeutic area where innovation is both medically and financially rewarding. With the global SMA market expected to surpass $2.2 billion by 2032, Biogen's ability to navigate regulatory hurdles and differentiate its offering will determine whether this high-dose strategy unlocks new value—or becomes another footnote in the race to treat rare diseases.