A trial of Biogen’s spinal muscular atrophy (SMA) therapy Spinraza (nusinersen) suggests that a higher dose provides benefits to a broad range of patients—including those who have and have not been treated, as well as patients with early- and late-onset variations of the disorder.
The company said that, based on the results, it will submit regulatory applications around the world for approval of the higher dose of Spinraza.
A month ago, Biogen reported that the pivotal Part B of its phase 2/3 DEVOTE study met its primary endpoint as the higher dose of Spinraza significantly improved the motor function of newly diagnosed infants with SMA compared to a prespecified matched sham (untreated) group from the ENDEAR study, which set up Spinraza for approval eight years ago.
Now, the company is showing additional results of the new treatment regimen, which includes starting doses two weeks apart at 50 mg, followed by 28 mg maintenance doses every four months, versus the currently approved formula in which patients receive 12-mg doses, including four to start followed by one every four months.
Biogen reported the data at World Muscle Society Congress Tuesday in Prague.
“While we’ve seen great progress over the past decade in improving the lives of those with SMA, gaps remain and we can do more to address the full range of unmet needs and goals within our community,” Kenneth Hobby, president of Cure SMA, said in the release. “The DEVOTE study’s findings are promising and show the potential for additional meaningful advancements that could further enhance motor function.”
The size of the three-part DEVOTE study, which included 145 participants from a wide range of ages and SMA types, made comparisons difficult. In addition to comparisons between the high dose group and the untreated group from the old trial, there also were comparisons between the high-dose group and those in the DEVOTE study who were on the approved 12-mg regimen. These were not “adequately powered,” however, to detect conclusive differences between the groups, Biogen said.
Data still favored the higher-dose regimen. For example, the higher dose provided a 94% reduction in plasma neurofilament light chain (NfL)—which is a marker for neurodegeneration—from baseline to Day 183 compared to a 30% reduction in the sham control group. Additionally, at day 64, more rapid NfL reductions were seen with the higher-dose group versus those who received the 12 mg dose.
“Strikingly, the higher dose regimen lowered neurofilament more quickly, telling us that it’s more rapidly slowing neurodegeneration. We know how critical this is in people living with SMA,” Thomas Crawford, M.D., co-director of the Muscular Dystrophy Association Clinic at Johns Hopkins Medicine, said in a release.
Importantly, Crawford also noted that the higher dose regimen had the same safety profile as the with 12-mg regimen.
The higher dose regimen also reduced the risk of death or permanent ventilation by 68% relative to sham and 30% relative to the 12 mg regimen, with a similar pattern observed for overall survival, hospitalizations and serious respiratory events.
There also were some head-scratching results, such as the 12-mg regimen showing greater improvement at Day 302 than the high-dose regimen on the CHOP-INTEND motor skills test. In another type of motor skills and neurological evaluation measure, the Hammersmith Infant Neurological Exam section 2 (HINE-2), those on the high-dose regimen scored higher than their 12-mg counterparts.
Biogen reported blockbuster sales for Spinraza in its second full year on the market (2018). Sales peaked at $2.1 billion in 2021 but 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.