Positive Results Reported for High-Dose Spinraza
Data from the DEVOTE study suggest that 50-milligram doses are safe and effective.
New data is showing the promise of using higher doses of Spinraza (nusinersen) for treatment for with spinal muscular atrophy (SMA).
Topline data from the pivotal Part B cohort of the phase 2/3 DEVOTE study showed that treatment with a higher dose of Spinraza met its primary end point at six months, achieving a statistically significant improvement in motor function among treatment-naïve symptomatic infants relative to a prespecified matched sham control group from the phase 3 ENDEAR study, according to a Biogen news release.
The higher dose of Spinraza being investigated is comprised of two separate 50-milligrams (mg) doses at two weeks apart, and a higher maintenance regimen of 28-mg every four months, compared with the approved Spinraza regimen of 12 milligrams.
In the trial, the higher dose cohort revealed significant improvement statistically over the matched sham comparator on the primary end point of change in Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) from baseline to six months.
Stephanie Fradette, Pharm.D.
“While there has been remarkable progress in the treatment of SMA, there remains significant unmet need. Building on the well-characterized profile of Spinraza established over the past 10 years, we continue to explore the potential for maximizing efficacy outcomes while maintaining our commitment to safety,” Stephanie Fradette, Pharm.D., head of the neuromuscular development unit at Biogen, said in the news release.
The three-part DEVOTE study included145 participants across ages and SMA types. In the Part B cohort, researchers randomized treatment-naïve children with infantile-onset SMA 2 to 1 to be given the higher dose of Spinraza or the approved 12-mg regime, which comprised of four loading doses and maintenance doses every four months.
The primary end point of Part B was the change from baseline on the CHOP-INTEND at six months with the higher dose regimen of Spinraza in comparison with a matched, untreated sham control group from the phase 3 ENDEAR study, which was one of the two pivotal studies that formed the basis of regulatory approval for Spinraza.
Additional findings favored the higher dose regimen compared with the sham according to a number of secondary end points Overall, the higher dose regimen was generally well tolerated among the participants, with adverse events experienced by patients generally consistent with SMA as well as the known safety profile of Spinraza, according to the Biogen news release. The findings showed that the percentage of serious adverse events was lower in the higher dose regimen group (n = 30, 60%) as compared with the 12 mg group (n = 18, 72%).
Further details on the results from DEVOTE trial will be presented at upcoming medical conferences, Biogen said.
When Spinraza was approved by the FDA in December 2016 it was first approved drug for the treatment of SMA in pediatric and adult patients in December 2016.
Spinraza is an antisense oligonucleotide that targets the cause of SMA by continuously increasing the amount of full-length survival motor neuron protein produced in the body. It is administered directly into the central nervous system.
In a response to a survey, caregivers of people with spinal muscular atrophy identified the risk of severe adverse events and the need for permanent ventilation as the most important factors in treatment decisions. Access to treatment, including cost and availability, ranked third.
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