Biogen's High-Dose Nusinersen: A Game-Changer for SMA Therapy and Shareholder Value

The SMA (spinal muscular atrophy) treatment landscape is undergoing a transformative shift, with Biogen's high-dose nusinersen (SPINRAZA) emerging as a pivotal contender. Following the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommending approval of the high-dose regimen for 5q SMA in November 2025, the therapy now awaits final European Commission approval by January 2026. Simultaneously, the U.S. Food and Drug Administration (FDA) has set a decision date of April 3, 2026, for its review, despite issuing a Complete Response Letter (CRL) in September 2025 citing Chemistry, Manufacturing, and Controls (CMC) issues according to Biogen's investor update. This regulatory progress, coupled with robust clinical data from the DEVOTE study, positions the high-dose regimen as a potential catalyst for Biogen's growth and Ionis Pharmaceuticals' collaboration value.

Clinical Efficacy and Regulatory Momentum

The DEVOTE study, which evaluated the high-dose regimen in treatment-naïve infants, demonstrated a statistically significant improvement in motor function, as measured by the CHOP-INTEND score. Participants receiving the regimen (two 50 mg loading doses followed by 28 mg every four months) showed a mean difference of 26.19 points compared to a prespecified sham group (p < 0.001) according to clinical data. These results, combined with the CHMP's positive opinion, underscore the therapy's potential to address unmet needs in SMA treatment.

However, the FDA's CRL highlights a critical hurdle: technical manufacturing challenges rather than clinical data deficiencies. Biogen has committed to resubmitting the application promptly, emphasizing that the high-dose regimen's clinical profile remains intact according to Biogen's regulatory update. This bifurcated regulatory timeline-approval in Europe by early 2026 and a pending U.S. decision-creates a strategic window for Biogen to expand its market presence in key regions while addressing technicalities in the U.S.

Financial Collaboration and Partnership Value

Biogen's collaboration with Ionis Pharmaceuticals, which licensed global rights to nusinersen in 2016, remains central to the high-dose regimen's commercialization. Ionis has already earned over $435 million from Biogen through milestone payments and royalties according to Ionis' financial report. In Q2 2025 alone, SPINRAZA generated $393 million in global sales, translating to $54 million in royalty revenue for Ionis according to Ionis' Q2 2025 results. The high-dose regimen, if approved, could unlock additional milestones, particularly in Japan, where the therapy was recently approved according to Biogen's regulatory update.

The partnership's financial structure also includes a 2023 monetization agreement with Royalty Pharma, which acquired a portion of Ionis' SPINRAZA royalty stream for up to $1.1 billion according to Ionis' royalty agreement. While Ionis retains the majority of royalties, this arrangement underscores the drug's enduring commercial value, even as the low-dose version faces competition from newer therapies like Roche's Evrysdi and Novartis' Zolgensma. Analysts project a 50% decline in SPINRAZA sales by 2031, but the high-dose regimen could mitigate this trend by offering improved efficacy and broader patient eligibility.

Market Expansion and Competitive Dynamics

The SMA market is poised for explosive growth, driven by advancements in gene and RNA-based therapies. By 2032, the market is projected to reach $16.28 billion, with a 17.87% compound annual growth rate according to market research. Evrysdi's oral administration and broad eligibility have made it a market leader, while Zolgensma's one-time gene therapy model appeals to patients seeking long-term solutions. However, both therapies face challenges: Zolgensma's high cost and Evrysdi's patent expiration post-2030 according to competitive analysis.

Biogen's high-dose nusinersen could carve a niche by balancing efficacy with a manageable safety profile. The regimen's intrathecal administration, though less convenient than oral therapies, offers a well-established safety record and over a decade of real-world data according to Biogen's regulatory update. In regions with robust reimbursement frameworks, such as the U.S. and Europe, this could position the high-dose version as a preferred option for patients who require frequent dosing or cannot access gene therapy.

Conclusion: Balancing Opportunity and Risk

Biogen's high-dose nusinersen represents a strategic pivot in the SMA treatment ecosystem. While the FDA's CRL introduces near-term uncertainty, the CHMP's endorsement and strong clinical data provide a clear path to European approval. For Biogen, successful resubmission of the U.S. application could reinvigorate SPINRAZA's commercial prospects, countering the erosion of its market share. For Ionis, the collaboration continues to deliver steady royalty revenue, with the high-dose regimen potentially extending the drug's lifecycle.

Investors should monitor the April 2026 FDA decision and the European Commission's January 2026 ruling as key inflection points. In the broader SMA market, the interplay between Biogen, Roche, and Novartis will shape competitive dynamics through the late 2020s. For now, the high-dose nusinersen stands as a testament to the evolving value of RNA-based therapies in rare disease treatment.