High-dose Spinraza safely boosts motor function in SMA children: Data
Decision on application seeking US approval of dosage expected in April
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- High-dose Spinraza safely improved motor function in children with SMA, as shown in the DEVOTE clinical trial.
- Patients previously on the standard Spinraza dose also saw motor function improvements after switching to the higher-dose regimen.
- This high-dose treatment is approved in Europe/Japan, with a US approval decision expected in April.
Treatment with a high-dose regimen of Spinraza (nusinersen) was shown to safely improve motor function in children with spinal muscular atrophy (SMA) in the Phase 2/3 DEVOTE clinical trial.
Most patients who switched from the originally approved dose to the high-dose regimen experienced improvements in motor function scores, data also showed.
Biogen, the company that sells Spinraza and funded the study, previously announced positive top-line results from DEVOTE. Now, the findings have undergone peer review — the process in which other scientists review the study — and been published in Nature Medicine in a paper titled, “High-dose nusinersen for spinal muscular atrophy: a phase 3 randomized trial.”
“The publication of the DEVOTE data [is] an important step in our commitment to bring the [high-dose] regimen of [Spinraza] to people living with SMA as quickly as possible,” Stephanie Fradette, head of the neuromuscular development unit at Biogen, said in a company press release. “We are grateful to the participants, their families, study investigators and site staff, and our co-authors who have made the DEVOTE study and publication of these results a reality.”
Sprinraza first treatment proven to slow SMA progression
Based in part on data from DEVOTE, the high-dose regimen of Spinraza was recently approved in the European Union and Japan. An application seeking approval in the U.S. is currently under review, with a decision expected in April.
Spinraza was the first treatment proven to slow SMA progression in clinical trials, leading to approvals in the U.S. and many other countries worldwide. It is given by injection into the spinal canal, known as an intrathecal injection. Under its original approval, each injection delivered 12 mg of the therapy. The first three injections are given every two weeks, followed by the fourth a month later. Injections are then given every four months thereafter.
The high-dose regimen instead starts with two 50 mg doses two weeks apart, followed by 28 mg doses every four months. The DEVOTE study (NCT04089566) was designed to evaluate the safety and effectiveness of this regimen.
After an initial safety test, the pivotal portion of DEVOTE (part B) included 75 infants with SMA who had not been treated. They were randomly assigned to receive Spinraza at the originally approved dose or with the high-dose regimen. The main goal of this part of the study was to see if patients given the higher dose of Spinraza would have better motor function outcomes than children given a placebo in ENDEAR (NCT02193074), a prior Phase 3 trial that supported the first approvals of Spinraza.
The trial met its main goal. After six months, the mean score on the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), a standard measure of motor function, improved by 15.1 points in children given the high-dose Spinraza regimen. By contrast, among patients given the placebo in ENDEAR, mean CHOP-INTEND scores worsened by 11.1 points in the same time frame.
Treatment with high-dose regimen led to improvement across several domains
The study, notably, wasn’t designed to directly compare and detect statistically significant differences in outcomes between the two tested doses of Spinraza. Still, the researchers noted that motor function scores tended to show greater improvements in patients given the high-dose regimen.
“One of the most notable changes seen with the [higher-dose] regimen was a more rapid reduction in neurofilament, a marker of neurodegeneration. In DEVOTE, treatment with the high-dose regimen led to improvement across important domains like motor and bulbar [mouth-and-throat] function, respiratory health and hospitalizations, and survival,” said Richard Finkel, MD, lead author of the study at St. Jude Children’s Research Hospital.
The study’s part C included 40 SMA patients who had previously been on the original Spinraza dosage for a median of 3.9 years but switched to the higher-dose regimen in DEVOTE. In these patients, motor function was assessed using two measures: the Hammersmith Functional Motor Scale Expanded (HFMSE), which evaluates overall motor function, and the Revised Upper Limb Module (RULM), which specifically assesses arm and hand function.
[Data from DEVOTE] support the potential of the high-dose regimen of [Spinraza] to provide greater benefit compared with the [originally-approved] regimen while maintaining a similar safety profile.
Data showed that, after about 10 months, more than half (53%) of the patients had improved HFMSE scores. Among patients who didn’t have perfect RULM scores at the start of the trial, nearly two-thirds (62%) showed improvement in this score after switching to the high-dose regimen.
“Some participants were at the upper end of HFMSE and RULM scoring at baseline; thus, they may have had a limited opportunity for additional improvement in scores. Regardless, observed improvements on HFMSE and RULM … exceeded what would be expected in a population that had been on [Spinraza] for several years,” the researchers wrote.
Safety data for the high-dose regimen of Spinraza were broadly consistent with the known profile of the originally approved dose, the researchers said. Overall, the scientists concluded that data from DEVOTE “support the potential of the high-dose regimen of [Spinraza] to provide greater benefit compared with the [originally approved] regimen while maintaining a similar safety profile.”
