- Pre-symptomatic patients with the most severe form of spinal muscular atrophy showed sustained improvement following intravenous treatment with Novartis' experimental gene therapy Zolgensma, according to a data presentation at the American Academy of Neurology.
- The Swiss company also detailed the first interim data from a trial in older and less severe patients, showing that they experienced improved motor function following a dose of Zolgensma delivered into the spinal fluid. Three of 30 patients in this trial so far have gained the ability to stand or walk.
- Zolgensma is due for a Food and Drug Administration decision this month and, if approved, will take on Biogen's Spinraza in SMA, which is caused by genetic mutations that lead to degeneration of motor neurons and progressive muscular weakness. In the most severe form, patients seldom live past the age of 2.
Novartis appears poised to achieve an FDA approval for its gene therapy Zolgensma (onasemnogene abeparvovec) in the most severe form of the disease, Type 1, later this month.
But the pharma will not be stopping there as it builds a data package that could allow it to expand into less severe forms of the disease. In such patients, incomplete mutations allow for some motor neuron function.
The American Academy of Neurology's annual meeting in Philadelphia provided a venue to present its case. Novartis detailed updated data from the key STR1VE study in babies identified as Type 1 by genetic screening and who receive an intravenous dose of Zolgensma before symptoms appear. This study began enrolling in late 2017.
As of March 8, 11 of 22 patients enrolled were able to sit without support for 30 seconds or more, marking an improvement from the Dec. 31 data cut when eight could do so. Using an objective measure motor milestones called CHOP-INTEND, the patients in STR1VE had improved by a little more than 14 points on the 64-point scale five months following treatment. The Dec. 31 data analysis showed they had improved by nearly 12 points at three months.
The data are on par with those from the START trial in symptomatic patients that's now being reviewed by the FDA. Identifying patients using genetic testing may become easier in the U.S. as states roll out genetic SMA screening following federal government recommendations. David Lennon, president of Novartis' AveXis subsidiary, said about 15% of babies are currently screened for the condition.
Expanding that number will be essential for the next steps of Novartis' strategy, namely treatment of the less severe Type 2 and 3 patients. Although Type 1 is the most common form of SMA — representing about 60% of the 400 to 500 SMA births in the US every year — the disease's high and early mortality means there are only about 1,000 living Type 1 patients at any time. Type 2 represents roughly 30% of SMA births, but about 6,000 of the 9,000 to 10,000 living SMA patients have that form of the disease.
Novartis also released the first data from its SPR1NT study in pre-symptomatic patients younger than six weeks of age with two or three copies of the SMN2 gene. (The number of copies is inversely related to the severity of the disease.)
Eight of 18 patients enrolled as of March 8 had two copies of SMN2, and saw a nearly nine-point average improvement in CHOP-INTEND one month after dosing. Four could sit without support for 30 seconds.
"Once motor neuron death occurs it is irreversible. So what we want to do is not just halt the disease, but we also want to halt it before any motor neuron damage occurs," Olga Santiago, chief medical officer of AveXis, said in a call with reporters. "To do that we need to do that before there are any symptoms, diagnosing at the time of birth, as we have done in the SPR1NT study."
A third trial, in older patients with three copies of the SMN2 gene who received a dose into the spinal fluid, could provide an opportunity to expand further. These patients were divided into two groups by age, between six and 24 months, and 24 months to 60 months.
In the younger group, two patients gained the ability to stand and one to walk without assistance, and in the older group, one gained the ability to walk with assistance. In the older group, six of 12 patients gained three points or more on a measure called the Hammersmith functional motor scale one month after treatment.
Asked about a patient death in a European version of the STR1VE trial, the company said it had no further information about the cause.
Novartis paid $8.7 billion to acquire AveXis last year.