Biogen to seek approval for high-dose Spinraza after trial success

Biogen is seeking to rejuvenate its flagship spinal muscular atrophy (SMA) medication, Spinraza, by developing a high-dose version amid declining sales. Over the past decade, Spinraza, along with Roche’s Evrysdi and Novartis’ gene therapy Zolgensma, has significantly advanced SMA treatment. Despite these innovations, there remains a pressing need for more effective treatments.

Biogen, which secured initial approval for Spinraza in 2016, is now focusing on a higher-dose variant to enhance patient outcomes. Recently, the company announced that part of its phase 2/3 DEVOTE study met its primary goal, with the higher-dose version showing improved motor function in treatment-naïve infants with SMA.

In Part B of the DEVOTE trial, patients received an initial two doses of 50 mg of nusinersen, spaced 14 days apart, followed by maintenance doses of 28 mg every four months. This regimen led to significant improvements in patient mobility, as measured by the Children’s Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) metric. The study compared this new high-dose regimen to an untreated sham control group from the phase 3 ENDEAR study, which was instrumental in Spinraza's original approval.

Within the DEVOTE trial's cohort, 75 patients were randomized in a 2:1 ratio to receive either the higher-dose regimen or the FDA-approved 12 mg dosage. The standard dosage includes four initial treatments followed by maintenance doses every four months. While the high-dose version succeeded in meeting the trial's primary endpoint compared to the sham group, it also showed favorable trends against the currently approved dosage in key biomarker and efficacy measures.

Biogen plans to seek regulatory approval for this new dosage regimen. The higher-dose version was generally well tolerated, with adverse events consistent with those expected in SMA and Spinraza's known safety profile. Notably, the percentage of serious adverse events was lower in the high-dose group (60%) compared to the 12 mg group (72%).

These promising results come from one segment of Part B of the trial, which includes infantile-onset patients and is viewed as the pivotal part of the study. The other segment of Part B focuses on later-onset SMA patients. Part A of the DEVOTE study assesses the safety of the higher-dose regimen, while Part C evaluates the safety and tolerability of transitioning patients from the approved dose to the higher-dose regimen.

Spinraza works by increasing levels of survival motor neuron (SMN) protein, which is vital for the health of motor neurons responsible for controlling voluntary muscle movement. Biogen's efforts to boost Spinraza's efficacy come as sales have declined from a peak of $2.1 billion in 2021 to $1.7 billion last year.

The competitive landscape also includes Novartis’ Zolgensma, which saw sales peak at $1.4 billion in 2022 before declining to $1.2 billion last year, and Roche’s Evrysdi, which has shown continuous growth, reaching sales of 1.42 billion Swiss francs ($1.7 billion) in 2023.

By pursuing a higher-dose version of Spinraza, Biogen aims to address the ongoing unmet needs in SMA treatment and potentially revitalize the drug's market performance.

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