AveXis, a Novartis company,announced that interim data from its Phase 3 STR1VE trial of Zolgensma® (onasemnogene abeparvovec-xioi; AVXS-101)[1] in spinal muscular atrophy (SMA) Type 1 showed prolonged event-free survival, an early and rapid increase in CHOP-INTEND scores and significant milestone achievement compared to untreated natural history, consistent with data from the pivotal Phase 1 START trial. First-in-human biodistribution individual case study data from STR1VE showed Zolgensma successfully transduced intended targets in the central nervous system (CNS) and provided widespread SMN expression comparable to tissue from unaffected individual. Additional data presented showed 95 percent of patients screened across the Zolgensma clinical development program and Managed Access Program were not excluded from treatment due to elevated AAV9 antibody titers greater than 1:50. These data were presented today at the 2019 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference in Orlando, Florida.

"These STR1VE data reinforce what was seen in the pivotal Phase 1 START trial, including trends toward prolonged survival and milestone achievement never seen in the natural history of the untreated disease," said Olga Santiago, MD, Chief Medical Officer, AveXis. "With a patient population and baseline characteristics closely matched to the START trial, these data build upon the body of evidence supporting the use of Zolgensma for SMA Type 1."

Interim Phase 3 STR1VE Data as of September 27, 2018
STR1VE is an ongoing, open-label, single-arm, single-dose, multi-center trial designed to evaluate the efficacy and safety of a one-time intravenous infusion of Zolgensma in patients with SMA Type 1 who are less than six months of age at the time of gene therapy. The study was designed to enroll the broadest possible population of SMA Type 1 patients with one or two copies of the SMN2 backup gene and who have bi-allelic SMN1 gene deletion or point mutations. These criteria are well-matched to the patient population that was enrolled in the pivotal Phase 1 START trial while potentially providing treatment to some of the rarer subpopulations on an exploratory basis. STR1VE is projected to complete in 2020.

As of September 27, 2018, 21 of 22 (95 percent) patients were alive and event-free.[2] The median age was 9.5 months, with 6 of 7 (86 percent) patients who could have reached 10.5 months of age or older surviving event-free. Untreated natural history indicates that 50 percent of babies with SMA Type 1 will not survive or will require permanent ventilation by the time they reach 10.5 months of age[3].

Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores increased by an average of 7.0 points one month after gene transfer and 11.8 points three months after gene transfer, reflecting improvement in motor function from baseline. These data are similar to CHOP-INTEND achievement by the proposed therapeutic dose cohort (Cohort 2) in the pivotal START trial, which demonstrated mean increases of 9.8 and 15.4 points at the same time points, respectively. Early CHOP-INTEND increases appear to be associated with eventual milestone achievement.

Preliminary assessments of patients treated with Zolgensma showed the achievement of motor milestones, including three patients who could sit without support for at least 30 seconds as of September 27, 2018 (median of 9.4 months), increasing to eight patients who could achieve the same milestone as of December 31, 2018 (median age of 12.5 months).

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