Biogen's SMA Pipeline Dominance: Dosing Innovation and Synergy Fuel Long-Term Growth

The race to dominate spinal muscular atrophy (SMA) therapeutics has long been a high-stakes arena, with Biogen's SPINRAZA (nusinersen) reigning as the standard of care since its 2016 FDA approval. Now, new data from Biogen's DEVOTE Part C trial and Phase 1 results for its next-generation therapy salanersen are cementing the company's leadership. By optimizing dosing regimens to extend functional benefits and introducing a novel treatment that synergizes with gene therapies, Biogen is securing its position as the SMA market's clear leader. For investors, this is a compelling case for sustained growth.

The Case for Higher Doses: SPINRAZA's Extended Efficacy

The DEVOTE Part C trial, presented in June 2025, delivers critical evidence that a higher-dose regimen of nusinersen can provide incremental gains for patients with long-standing SMA. The study focused on 38 participants who had been on the standard 12 mg dose for nearly four years. The new regimen—a loading dose of two 50 mg injections 14 days apart, followed by 28 mg maintenance doses every four months—showed statistically significant improvements in motor function. Non-ambulatory patients gained an average of +2.5 points on the Hammersmith Functional Motor Scale – Expanded (HFMSE), a clinically meaningful milestone. Even ambulatory patients saw modest but measurable gains, with +1.1 points on the HFMSE, signaling broader applicability.

The data are particularly compelling because they demonstrate efficacy in patients who had already plateaued on the standard dose. Dr. Richard Finkel, a principal investigator, emphasized that these results could “fundamentally change how we treat our patients,” suggesting the higher dose could delay disease progression further. With the FDA and EMA reviewing the application for this regimen, approval could expand SPINRAZA's addressable market, capturing patients who have exhausted earlier gains.

Salanersen: Once-Yearly Dosing and Synergy with Gene Therapies

While SPINRAZA's optimization targets existing patients, salanersen (BIIB115/ION306) aims to address unmet needs in SMA's evolving treatment landscape. Phase 1 data reveal a drug designed for once-yearly dosing, a stark contrast to SPINRAZA's every-four-month injections. The therapy's mechanism mirrors nusinersen's, but with enhanced potency, potentially reducing the burden of frequent infusions.

The trial's starkest finding came from SMA patients who had received ZOLGENSMA (onasemnogene abeparvovec), a gene therapy, but still showed neurodegeneration. Salanersen reduced neurofilament light chain (NfL) levels—a biomarker of neuronal damage—by 70% at six months, sustained through 12 months. Clinically, 50% of participants achieved new motor milestones, such as sitting or walking, with mean improvements of +3.3 points on the HFMSE and +5.3 on the RULM. These results suggest salanersen could complement gene therapies, addressing cases where ZOLGENSMA alone falls short.

Why This Matters for Investors

Biogen's dual-pronged strategy—improving its flagship drug and introducing a novel, less-frequent therapy—creates a moat against competitors like Roche (ROCHE) and Novartis (NVS), whose offerings (risdiplam and ZOLGENSMA) face headwinds from pricing pressures and efficacy limitations. The higher-dose SPINRAZA could extend its lifecycle, while salanersen's once-yearly dosing and synergy potential could carve out a niche in combination therapies.

The financial upside is substantial. SPINRAZA's global sales totaled $1.3 billion in 2024, but higher-dose approvals could boost adherence and pricing power. Meanwhile, salanersen, if successful, could add $1 billion+ in annual revenue by 2030, especially as gene therapy use expands.

Risks and Considerations

The higher-dose SPINRAZA trial reported a high incidence of adverse events (37/40 participants), though none were deemed treatment-related. Salanersen's Phase 1 safety profile was favorable, but larger trials will be critical. Additionally, competition remains fierce, and pricing negotiations with payers could constrain margins.

Investment Thesis

Biogen's SMA pipeline is now a two-engine growth driver. The higher-dose SPINRAZA reinforces its current franchise, while salanersen positions it to lead the next wave of SMA innovation. With regulatory decisions expected in 2025–2026, the near-term catalysts are clear. For investors, this is a “buy and hold” opportunity: Biogen's dominance in SMA—backed by clinical differentiation and strategic pipeline depth—justifies a premium valuation.

Final Call: Consider accumulating Biogen shares on dips, targeting the $280–$300 range, with a long-term price target of $400+ by 2028. The SMA market is growing, and Biogen is writing its rules.