AAN 2023: Spinraza shows benefits in clinical trial of SMA adults
In adults with spinal muscular atrophy (SMA), treatment with Spinraza (nusinersen) in a clinical trial was tolerated well and led to improvements in arm function and self-rated health.
These findings add to data from several studies that have examined the safety and efficacy of Spinraza in older patients following the drug’s approval. No adults were enrolled in the key clinical trials that led to the therapy’s approval in 2016 in the U.S. and 2017 in Europe.
“I think this [result] is encouraging,” Chad Heatwole, MD, from the University of Rochester Medical Center, said at this week’s American Academy of Neurology (AAN) 2023 Annual Meeting, held April 22-27 in Boston and virtually.
“Initially, [Spinraza] was approved for adults without a lot of data in adults with SMA, and I think this shows, at the very least, that it’s safe in this population [and] that patients’ disease burden … is improving,” Heatwole said.
The scientist discussed these data at AAN in a talk titled, “Spinraza in Adults with Spinal Muscular Atrophy (SAS) – 14 month results.” The research was funded by Biogen, which markets Spinraza.
SAS trial testing therapy’s safety, efficacy in adults
Spinraza was the first therapy to be widely approved to treat SMA. Administered via regular injections through the spine, it helps boost production of the SMN protein that’s lacking in people with SMA. It works by modulating the activity of SMN2, a backup form of the SMN1 gene whose mutations cause SMA.
Approvals of Spinraza in the U.S. and many other countries authorized the use of the treatment in people of all ages with SMA. However, the clinical trials that formed the basis for its approval exclusively included children with relatively severe types of SMA.
To learn more about how treatment with Spinraza affects adults with milder forms of the disease, the Washington University School of Medicine, in St. Louis, Missouri, is sponsoring a clinical trial called Spinraza in Adult SMA, or SAS (NCT03709784).
“The SAS trial … is designed to look at the safety and efficacy of [Spinraza] over 30 months in adults with type 2 and type 3” disease, Heatwole said. Compared with more severe disease forms, which significantly reduce live expectancy to a few months or years, patients with these milder forms of SMA typically live into adulthood.
The study’s main goals are to assess the impact of treatment on patients’ physical function. Specifically, for patients who have reduced arm function when they enter the study, the trial is evaluating scores on the Revised Upper Limb Module (RULM), a measure of arm and hand function. Among patients who are able to walk, the trial also is assessing the effect on Six Minute Walk Distance (6MWD), a measure of walking ability.
A total of 43 adults with SMA were enrolled in the study. All were starting on SMA treatment for the first time. About half of the patients were female, and the average age was in the mid-30s. Heatwole noted that fewer patients were enrolled than planned, due largely to complications arising from the COVID-19 pandemic.
In his talk, Heatwole shared interim data after 14 months, or just longer than one year of treatment.
Stable scores on walking tests contrast with expected worsening of ability
The RULM analysis included data for 32 of the patients, while the 6MWD analysis involved 14 patients. Three patients able to walk but with reduced arm function when they started the study were included in both analyses.
The results showed that scores on the RULM improved significantly, by 0.9 points at six months and one point after 14 months on Spinraza. Scores on the 6MWD, meanwhile, were stable throughout the study, with no clear improvement or worsening after 14 months on Spinraza.
Measures of lung function, as assessed with the forced vital capacity predicted measure, also were stable over the 14-month period analyzed.
Stable scores on walking and lung function tests are a marked contrast to the typical course of untreated SMA, Heatwole noted. Among patients not receiving treatment, these scores would be expected to worsen over time as the disease progresses.
Initially, [Spinraza] was approved for adults without a lot of data in adults with SMA, and I think this shows, at the very least, that it’s safe in this population [and] that patients’ disease burden … is improving.
Additionally, for both RULM and 6MWD, more patients experienced clinically meaningful improvements than worsening after 14 months, the data showed.
Among all evaluable patients, scores on the SMA-Health Index (SMA-HI) — a measure in which patients self-rate their own health and disease burden — improved significantly, denoting better health. Indeed, these scores increased by more than six points on average after 14 months of Spinraza treatment.
Scores on the Revised Hammersmith Scale, a measure of motor function, also tended to improve over the course of the study, though the difference was not statistically significant at 14 months.
Overall, safety data from this study have been consistent with prior research on Spinraza, with common side effects including headache, pain in the extremities, and upper respiratory tract infection. No serious side effects related to the medication were reported.
“So far in the study, [Spinraza] is shown to be generally safe and well tolerated in adults with SMA,” Heatwole said.
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