Novartis’ company Avexis said that it’s Phase 1/2 Srong study for intrathecal (IT) administration of AVXS-101, showed that patients aged 2 to 5, with spinal muscular atrophy (SMA) Type 2 achieved a mean increase of 5.9 points from baseline in HFMSE scores, nearly double the clinically meaningful threshold, at a mean duration of follow-up time of 9.3 months.
Novartis said that this is up from a mean increase of 4.2 points from baseline in HFMSE scores presented in May 2019 at the American Academy of Neurology Annual Meeting. The company said that study showed half of the older patients with SMA Type 2 experienced a clinically meaningful response in motor function gains starting at one month post-treatment, defined as a 3-point or more increase from baseline in HFMSE scores.
HFMSE is a well-recognized functional scale used clinically and in clinical trials to measure physical abilities and motor function in non-ambulatory and ambulatory individuals with SMA Type 2 and 3, Novartis said. These data were presented at the 24th World Muscle Society (WMS) annual congress.
This rare and genetic disiease is suchthat many children will never stand or walk independently without therapeutic intervention. Douglas M. Sproule, vice president MSA Therapeutic Head at AveXis said that today’s results – although early – are extremely encouraging for families who hope to see their children with SMA Type 2 experience meaningful improvement in motor function and important milestones, like standing and walking, following a one-time intrathecal administration of AVXS-101.
Sproule, said that these data presented at the congress, along with long-term follow-up data from the STR1VE and SPR1NT studies, support a continually advancing body of evidence on the clinical impact gene therapy treatment may have for those fighting this devastating and rare genetic disease, regardless of type or severity.
The company presented the results which also showed that in patients from 6 months to 2 years old, the primary efficacy endpoint is the ability to stand without support for more than 3 seconds. The secondary efficacy endpoint is the ability to walk independently for more than 5 steps, according to the Bayley-III Gross Motor Milestone Scale.
Novartis said that, since treatment, 18 motor milestones were achieved among the 16 patients who received Dose A or Dose B, including two patients who gained the ability to stand independently, one of whom went on to walk alone.
In patients aged 2 to 5, the primary efficacy endpoint is change in HFMSE score from baseline, while the secondary efficacy endpoint is the ability to walk independently for more than 5 steps according to the Bayley-III Gross Motor Milestone Scale, the company said.
Furthermore, patients showed a clinically meaningful improvement in motor function, having a mean 5.9-point increase from baseline in HFMSE scores at their most recent visit, at a mean duration of follow-up time of 9.3 months.
Since treatment, four motor milestones have been achieved among 12 patients in the Dose B group, including one patient who gained the ability to walk with assistance, the company said.
As for treatment emergent adverse events (TEAE), all patients in STRONG study experienced at least one TEAE, and 13 patients (43%) were reported to have a TEAE considered by the investigator to be related to treatment, Novartis said.
Serious TEAEs were reported in 13% (n=4) of patients. A total of seven serious TEAEs were reported in four patients (n=1 each): influenza, pneumonia, respiratory syncytial virus infection, elevated ALT, elevated AST, blood alkaline phosphatase increased, and respiratory failure. Elevated ALT and AST (in one patient) were considered probably related to treatment, Novartis said.
None of the serious TEAEs resulted in discontinuation from the study and no deaths were reported.
Investigational IT administration of AVXS-101 is currently being evaluated in patients with SMA Type 2 in a Phase 1/2 clinical trial.