Over the last decade, three blockbuster drugs—Biogen’s Spinraza, Roche’s Evrysdi and Novartis’ gene therapy Zolgensma—have transformed the treatment landscape for spinal muscular atrophy (SMA). Despite the advancements, there remains unmet need in the indication.
Biogen, which was first to score an approval in SMA in 2016, is attempting to address it with a higher dose version of Spinraza (nusinersen). On Wednesday, the company revealed that a portion of its phase 2/3 DEVOTE study met its primary endpoint, as a higher dose of Spinraza improved the motor function of treatment-naïve infants with SMA.
In Part B of the DEVOTE trial, two starting 50 mg doses of nusinersen taken 14 days apart—followed by 28 mg maintenance doses every four months—significantly improved the mobility of patients, as measured by the change from baseline on the Children’s Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) metric, according to Biogen.
The study compared the high-dose regimen to a matched, untreated sham control group from the phase 3 ENDEAR study, which enabled Spinraza's original approval.
In the DEVOTE trial cohort, 75 patients were randomized 2:1 to receive the higher-dose regimen or the FDA-approved dosage of 12 mg, which includes four starting treatments, followed by maintenance doses every four months.
While the high-dose version of Spinraza met the trial's endpoint compared to sham, the results also “trended in favor” of the investigational regimen compared to the currently approved dosage on key biomarker and efficacy measures, Biogen said.
Biogen plans to submit for regulatory approval of this investigational dose regimen, it said.
The higher-dose regimen was generally well tolerated, with reported adverse events generally consistent with SMA and the known safety profile of Spinraza. The percentage of serious adverse events was lower in the higher dose regimen (60%) as compared to the 12 mg group (72%).
The results are from one portion of Part B of the trial, which includes infantile-onset patients and is considered the pivotal part of the study. The other portion of Part B is for a later-onset cohort of SMA patients.
Part A of the DEVOTE study evaluates the safety of the higher-dose regimen while Part C of the trial assesses the safety and tolerability of transitioning patients from the currently approved dose to the higher-dose regimen.
Spinraza is designed to increase the levels of survival motor neutron (SMN) in people with SMA. SMN is essential for the health of motor neurons, the specialized nerve cells that control voluntary movement.
Biogen reported blockbuster sales for Spinraza in its second full year on the market. Sales peaked at $2.1 billion in 2021 and have declined since to $1.7 billion last year.
As for the competition, sales of Novartis’ Zolgensma, which was approved in 2019, peaked in 2022 at $1.4 billion before declining to $1.2 billion last year. Meanwhile, Roche’s Evrysdi, which was approved in 2020, has been on an upward trajectory, generating sales of 1.42 billion Swiss francs ($1.7 billion) in 2023.