Zolgensma didn't cause an infant death, AveXis execs say as they spotlight long-term data
Before the recent data manipulation scandal engulfed Novartis’ star gene therapy Zolgensma, the death of an infant in one of their Phase III trials threatened to sound safety alarms about the spinal muscular atrophy treatment. But scientists at the AveXis subsidiary now say an investigation has cleared that particular worry.
Nestled in a lengthy presentation of upbeat data, the update offers some much-needed validation for Zolgensma as execs scramble to rebuild their credibility with both regulators and the general public.
Out of the several studies touted at the European Paediatric Neurology Society Congress, there are a few key takeaways: Some of the earliest patients, as old as 5, are hitting developmental milestones in a long-term follow-up study; treating infants before they show any symptoms of SMA has allowed them to grow up in a way they otherwise never would have; and there’s more evidence that the gene therapy prevents symptomatic patients’ from worsening.
While the autopsy report findings didn’t feature up top, AveXis execs did take the time to address them in a call with reporters. After the British infant died in the STRIVE-EU study of a severe respiratory infection followed by neurological complications, the investigator thought the event might be related to treatment.
“We had been concerned about the potential… that Zolgensma might have been causing brain inflammation,” AveXis chief executive Dave Lennon said, as quoted by Reuters. “In this case, the original diagnosis, and that association, hasn’t held true.”
Although Zolgensma might have been responsible for other known side effects such as elevated enzymes in the liver, low platelets and low blood pressure, their investigation found no evidence of treatment-related brain damage. The conclusion: SMA Type 1 was the underlying cause for the infection, which in turn deprived the brain of oxygen and triggered hypoxic-ischemic brain damage.
Meanwhile, the rest of the results demonstrate the “life-changing impact Zolgensma can have on children with SMA Type 1” for families who never expected their children to crawl, sit or walk, said CMO Olga Santiago in a statement.
START, which started out as a 13-patient safety study, is now tracking 10 of those patients with a mean age of 4.2 years for whom treatment was on average 3.9 years ago. All are alive and the majority (seven) is not receiving Spinraza, Biogen’s SMA maintenance therapy. Six of them do not require daily respiratory support, and at least two are able to stand with assistance in addition to two others who were reported to be walking independently.
Serious adverse events were reported, affecting six out of the 13 original patients, but AveXis maintained that nothing was new.
In the SPR1NT study, patients were treated much younger — less than 6 weeks — as they tend to be diagnosed at birth. It’s only been a few months since the 23 patients were dosed, but among those with two copies of SMN2, six out of 10 were able to sit without support for at least 30 seconds — a co-primary endpoint. Overall, of the 22 being evaluated, all were alive without the help of permanent ventilation.
The final data cut won’t be taken until two years after treatment, yet these interim results show why it’s critical to diagnose SMA and intervene as early as possible, according to Santiago.
A separate Phase III global trial dubbed STR1VE is also watching for the 30-second sitting as a co-primary endpoint. There, so far, 50% of patients in the US trial and 6% in the EU trial has hit that goal — something that babies with SMA Type 1 would never be able to do, AveXis emphasized.
The other co-primary is event-free survival as measured by avoidance of death or permanent ventilation. The trial is scheduled to wrap later this year.