High-dose Spinraza treatment shown to safely benefit SMA infants
New dosing regimen significantly improved motor function: Trial data
Treatment with an investigational high-dose regimen of Spinraza (nusinersen) was well tolerated and significantly improved motor function in infants with spinal muscular atrophy (SMA) relative to untreated patients, according to top-line data from the pivotal portion of a Phase 2/3 clinical trial.
Results from the DEVOTE study (NCT04089566) also showed that this higher dose of Spinraza tended to outperform the lower dose of the therapy that’s already approved for treating SMA.
With these positive data now in hand, Spinraza’s developer Biogen said in a press release that it plans to seek regulatory approval of the new dosing plan. The company also said it will present additional results from DEVOTE at upcoming medical conferences — noting that the “higher dose regimen showed positive trends compared to the approved dosing regimen.”
“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,” said Stephanie Fradette, head of Biogen’s neuromuscular development unit.
“We look forward to sharing the detailed results with the SMA community and health authorities,” Fradette added.
New Spinraza treatment regimen is more rapid, with higher doses
Spinraza is a disease-modifying therapy that works to increase the levels of the SMN protein that SMA patients lack. It’s given via injections into the spinal canal, known as intrathecal administration.
In its approved treatment regimen, Spinraza is administered at a maintenance dose of 12 mg given once every four months. Before that are four initial loading doses: the first three are given once every two weeks, and the fourth is given a month later.
The investigational higher dosing regimen involves a more rapid loading dose regimen — two 50 mg doses spaced two weeks apart — and a higher maintenance dose of 28 mg every four months.
DEVOTE, designed to evaluate the safety and efficacy of this regimen, enrolled a total of 145 SMA patients across all ages and SMA types, and consisted of three parts.
Its second part, dubbed Part B, was a randomized, controlled phase that enrolled patients with infantile-onset and later-onset SMA. The 75 patients with infantile-onset SMA, ages 1 week to 7 months, were considered the trial’s pivotal cohort, meaning that the data from these patients are expected to mainly support regulatory applications.
These infants were randomly assigned to receive Spinraza treatment at either the investigational high dose or the approved lower dose.
Trial compared changes in motor function in untreated infants
The trial’s main goal was to compare changes in motor function, as assessed by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, known as CHOP-INTEND. The comparisons were made among patients in the high-dose Spinraza group after six months relative to an external untreated group — a sham group — from the Phase 3 ENDEAR trial (NCT02193074) that supported Spinraza’s initial approval.
This goal was met, with infants given the high dose of Spinraza seeing significant improvements in motor function relative to the external untreated group over six months. Specifically, Spinraza-treated patients exhibited a 26.19-point improvement in CHOP-INTEND scores relative to the sham group.
Secondary outcome measures similarly favored the high-dose regimen over the sham. Moreover, the high-dose Spinraza treatment tended to perform better than the standard approved regimen across key biomarker and efficacy measures, according to Biogen.
Among the benefits of high-dose Spinraza was a greater reduction in neurofilament, a biomarker of nerve damage, after about two months relative to standard Spinraza. According to Fradette, these “encouraging topline results … show that the higher dose regimen can slow neurodegeneration faster.”
[These] encouraging topline results … show that the higher dose [Spinraza] regimen can slow neurodegeneration faster.
The high-dose regimen was generally well tolerated among patients, with most reported side effects being consistent with SMA and the known safety profile of Spinraza. The percentage of serious adverse events was lower in the higher dose regimen than in the standard approved regimen (60% vs. 72%), the company noted.
Part A of the trial was an open-label safety study involving six SMA patients. Results published previously showed that the treatment was well tolerated and that most participants showed improvement or stabilization in motor function.
Part C enrolled SMA patients already using the approved dose of Spinraza. It was designed to evaluate the safety of switching to the high-dose treatment regimen.
Participants who complete any part of DEVOTE can enroll in a long-term extension study called ONWARD (NCT04729907), in which all will receive high-dose Spinraza for up to approximately five years.
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