Spinraza Plus Zolgensma Offers Little Extra Benefit in Type 1, Study Suggests
Combined treatment with Spinraza and Zolgensma does not markedly improve motor function or breathing ability in children with spinal muscular atrophy (SMA) type 1, a small, single-site study reported.
Its scientists highlighted that, regardless of the type of treatment given, earlier treatment leads to better outcomes.
The study, “Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I,” was published in the Journal of Clinical Medicine.
Zolgensma, by Novartis, is a one-time gene therapy that delivers a working copy of the SMN1 gene that is mutated in SMA to a patient’s cells. Spinraza, by Biogen, works by modulating the activity of a backup gene, SMN2, to help it produce more SMN protein; it is administered through regular intrathecal (spinal canal) injections.
While early data indicated that combined use of Spinraza and Zolgensma is generally well-tolerated, still to be decided is whether that combination yields benefits over time beyond those known to either therapy alone.
A team of scientists in Romania reported efficacy and safety data on two groups of SMA type 1 patients who were treated at their center.
Seven children (four boys, three girls) in the first group were treated with both Spinraza and Zolgensma. All but one of these patients started with Spinraza as a first therapy when they were 2 to 6 months old. The second group of six children (three boys, three girls) were treated with Spinraza only, also between the ages of 2 to 6 months.
Analyses of motor scores showed that patients given both therapies generally showed a much smaller improvement in motor function after the second therapy than that seen after the first treatment. The need for ventilation and cough assistance followed a similar trend.
Notably, in both the combination and Spinraza-only groups, patients tended to improve over time, with the most dramatic gains evident shortly after treatment was initiated.
“The trajectory curves [of motor scores] tend to show slower improvement after the first 6–12 months since the treatment was given, regardless of the type of therapy they received,” the researchers wrote.
Combining Spinraza and Zolgensma “does not seem to provide supplementary benefits for motor function or respiratory status,” they added.
Regardless of the type of therapy given, however, earlier treatment led to better outcomes over time, the researchers stressed.
“Our study showed that when we include the age of the patients when treatment was initiated and other parameters, treatment efficacy depends heavily on the timing of administration. Sooner is better—ideally, before symptom-onset,” they wrote.
Spinraza was generally well-tolerated among all the children in this study treated with it. The only reported side effect was mild agitation in two children in the Spinraza-only group, which the researchers suggested was attributable to a headache following its spinal injection administration.
All of the children dosed with Zolgensma experienced fever, vomiting, a lack of appetite, and abnormal levels of platelets (cell fragments that help with clotting) and liver enzymes. Two of them needed an increase in their dose of prednisone (an inflammation-suppressing steroid) to manage these symptoms.
One patient in the combination group had a severe reaction to Zolgensma, with bleeding, kidney failure, and respiratory arrest, and died about two months after receiving the therapy, the study noted.
Further studies into the safety of these treatments in SMA type 1 patients are needed, the scientists advised.