The FDA approved an intrathecal form of Novartis’ spinal muscular atrophy gene therapy Zolgensma on Monday, broadening access to patients two years and older in what one Stanford Medicine professor called a “game changing advance” for the field.
The FDA greenlit a new version of Novartis’ Zolgensma Monday, opening up the possibility of treatment with the groundbreaking spinal muscular atrophy gene therapy for older patients.
Itvisma—formerly known as onasemnogene abeparvovec-brve, or OAV101 IT—is an intrathecal [IT] form of Zolgensma, which was approved by the FDA in May 2019 as the first gene therapy for spinal muscular atrophy (SMA), for children 2 years and under. Conversely, Itvisma is approved to treat kids two years and older, teens and adults with spinal muscular atrophy (SMA) with a confirmed mutation in the survival motor neuron 1 (SMN1) gene. It is “the first and only gene replacement therapy” for this broader population, Novartis stated in its press release Monday.
Both formulations of Zolgensma address the genetic root cause of SMA by providing a functional copy of the SMN1 gene, which is lacking in these patients.
John Day, professor of Neurology and Pediatrics and director of the Division of Neuromuscular Medicine at Stanford University School of Medicine, called the approval a “game-changing advance” in SMA in a statement alongside Novartis’ press release, adding that “it also signals new possibilities for the broader field of neurological disorders and genetic medicine.”
The FDA’s greenlight for Itvisma was based on data from the Phase III STEER study and supported by the open-label Phase lllb STRENGTH study. Collectively, the studies showed “statistically significant” improvements in motor function and stabilization of motor abilities “typically not seen in the natural history of the disease,” according to Novartis. These effects were sustained over one year of follow-up.
As for safety, adverse events were consistent across both studies, with the most common in STEER being upper respiratory tract infection and fever and in STRENGTH, the common cold, fever and vomiting.
“When it comes to the mostly newborn, the young kids, we have seen transformative results there,” Norman Putzki, Novartis’ global development head of Neuroscience and Gene Therapy, told BioSpace in March. However, a more prevalent group of patients were “already too old . . . or too heavy to receive the treatment,” Putzki said.
He explained that intrathecal delivery makes the gene therapy safe for older, heavier patients.
With these patients, “You have a massively larger exposure, particularly towards the high end of the spectrum . . . that would require very high doses. So we can mitigate everything that is a dose-related toxicity by going IT with a small, flat dose into the [cerebrospinal fluid],” he said.
“The SMA disease landscape has dramatically changed over the last six years, when the first gene therapy was approved,” Kenneth Hobby, president of Cure SMA said in a statement on Monday.
Since 2019 when Zolgensma entered the market, the FDA has since approved Roche’s Evrysdi as the first tablet for SMA. Biogen’s antisense oligonucleotide Spinraza was approved in 2016 as the first-ever treatment for the neuromuscular disease.
