Infants likely to develop a severe form of spinal muscular atrophy, but who were not yet symptomatic, could sit and stand following treatment with Novartis' gene therapy Zolgensma, according to new study results disclosed by the Swiss drugmaker.
The data, presented Thursday at the European Paediatric Neurology Society's annual meeting in Athens, Greece, are an update from an initial glimpse the company gave in May.
Since then, more babies with the inherited neuromuscular disease achieved motor milestones like sitting independently for more than 30 seconds or standing with assistance. Typically, infants diagnosed with severe SMA are never able to sit, and most die by age two.
Five patients in the trial, called SPR1NT, achieved the maximum score on a University of Pennsylvania scale used to gauge motor abilities, an improvement from the three who did by the May update. Two others have reached normal levels.
"This is unprecedented and parallels normal childhood development," said Olga Santiago, chief medical officer at AveXis, on a call with reporters. AveXis developed Zolgensma until Novartis acquired the biotech last year for $8.7 billion.
The findings are further evidence of the benefit to giving Zolgensma soon after birth, before symptoms develop and motor neurons die.
"There's a dramatic difference between treating an infant in a presymptomatic stage, versus a two-month old who is symptomatic with SMA," said Russel Butterfield, a neurologist at the University of Utah and an investigator on two studies of Zolgensma, in an August interview with BioPharma Dive.
Zolgensma, which costs a record $2.1 million per patient, was approved in May for babies under age 2 with confirmed genetic mutations in the survival motor neuron (SMN) 1 gene that's missing in SMA patients.
So far, only 13 states in the U.S. currently do newborn screening for SMA, however, making earlier treatment before symptoms emerge and SMA is diagnosed more difficult.
SPR1NT enrolled infants with either two or three copies of a back-up gene that can preserve limited function. Babies born with two copies, 10 of whom participated in SPR1NT, are likely to develop the most severe, Type 1 form of SMA. Novartis also presented initial data on those with three copies, but most were younger than when infants typically sit or stand.
In a separate study of slightly older SMA infants, 11 of 22 could sit without support and one could crawl, pull up to standing and walk with assistance, as of May 31.
Novartis' presentation comes as the drugmaker attempts to recover from a damaging data scandal that called into question Zolgensma's approval.
In early August, the Food and Drug Administration revealed Novartis submitted manipulated testing data from mice in its application for Zolgensma. The company first learned of the altered preclinical results in March, two months before the therapy's OK, but proceeded without informing the agency.
The FDA continues to investigate, and has said it's confident Zolgensma should remain on the market. But the incident has marred what was a major achievement for Novartis and for the gene therapy field. AveXis could face civil or criminal penalties, the FDA has said.
"It does give me pause," said Utah's Butterfield. Still, he noted that physicians "have enough experience with the drug not to get too swayed by it."
While Novartis offered no new details on the data manipulation, it did give a fuller accounting of a patient who died in another study of Zolgensma, called STR1VE EU.
Originally, a preliminary assessment judged the death occurred in the context of a respiratory infection and leukoencephalopathy, then assessed as potentially related to Zolgensma.
Autopsy results, however, led to the recategorization of that neurological complication as hypoxic-ischemic brain damage stemming from lower blood pressure and the infection, Novartis said.
"We had been concerned about the potential, or the implication, that Zolgensma might have been causing brain inflammation in this case by the original diagnosis, and that association, which wasn't held [to be] true," said AveXis CEO David Lennon on a call with reporters.
Treatment with Zolgensma may have contributed to higher liver enzyme counts and possibly lower blood pressure, which were factors in the patient's hospitalization. Respiratory symptoms developed less than two weeks into study, prior to any assessment of gene therapy's efficacy, Novartis confirmed.
One other Zolgensma patient, enrolled in the U.S. counterpart study to STR1VE EU, died earlier this year following gene therapy infusion, but that was previously ruled unrelated to treatment.
Novartis also gave an update Thursday on long-term follow-up to its START study, which provided the principal support for Zolgensma's approval. Two infants newly gained the ability to stand with assistance, joining two others who are walking independently.
Importantly, no milestones achieved following treatment were lost among the 10 patients who continued study, who are now on average four years old.
Commercially, few data points are available on how Zolgensma has performed. Initial indications from insurers suggested pushback on the therapy's price, but Novartis has since said more than 20 commercial insurance plans have coverage policies in place.
Several hospitals involved in clinical testing of Zolgensma, including the University of Utah, confirmed dosing of commercial patients to BioPharma Dive.
Zolgensma faces competition from Biogen's rival SMA drug Spinraza, which was approved in 2016 as the first treatment for the disease.
Less than three years later, families and physicians have the choice between two treatments. Spinraza, which costs $375,000 per year, is taken for life, but more data is currently available supporting its safety and efficacy profile than is for Zolgensma.