Novartis announced that the U.S. Food and Drug Administration (FDA) has determined that OAV-101 intrathecal (IT) clinical trials for spinal muscular atrophy (SMA) patients may proceed, thereby lifting the partial clinical trial hold initiated in October 2019. The decision to lift the hold was based on data from Novartis’ comprehensive nonclinical toxicology study in non-human primates (NHP) that addressed all issues identified, including questions of dorsal root ganglia (DRG) injury following IT administration.
Following this decision and input from the FDA and European Medicines Agency (EMA), Novartis now plans to initiate STEER, a global pivotal, Phase 3 registration-enabling study to evaluate the clinical efficacy, safety, and tolerability of OAV-101 IT in treatment naïve patients who are between two and 18 years of age, able to sit, but have never walked. While disease progression is slower in patients with later-onset SMA, there are significant unmet needs.
STEER will build upon the Phase 1/2 STRONG study, which showed that treatment with OAV-101 IT led to significant increases in Hammersmith Functional Motor Scale-Expanded (HFMSE) scores and a clinically meaningful response in older patients between ≥2 years and <5 years old with SMA Type 2. Additionally, STEER will add to the clinical data and emerging real-world evidence for the use of gene therapy to treat SMA. Our intravenous formulation, Zolgensma® (onasemnogene abeparvovec) is approved in 41 countries.
STEER is a Phase 3 randomized, double-blind, sham-controlled study to evaluate the clinical efficacy, safety, and tolerability of a one-time intrathecal (IT) dose of OAV-101 in treatment naïve patients with Type 2 SMA who are between two and 18 years of age, able to sit, but have never walked. The primary objective of STEER is to evaluate the efficacy and safety of one-time IT administration of OAV-101 compared to sham controls over a 52-week period, at the end of which patients in the control arm will be treated with OAV-101. The therapeutic effect of OAV-101 will be evaluated using the Hammersmith Functional Motor Scale-Expanded (HFMSE). Secondary objectives include evaluating safety and efficacy of OAV-101 using the Revised Upper Limb Module (RULM) scale. More than 100 patients will be randomized to receive OAV-101 by IT injection or to receive a sham procedure. At the end of the 52-week period, all eligible patients who received the sham procedure will receive OAV-101 and all eligible patients who received OAV-101 will receive the sham procedure.
A sham-controlled study is a method used in clinical trials to help determine the effectiveness of a drug or treatment when a procedure is required, and has precedent in other Phase 3 studies measuring the efficacy of treatments for later-onset SMA. The use of a sham procedure in STEER is included to provide a comparison group for an unbiased collection and assessment of efficacy, safety and tolerability of OAV-101 IT for this older population where the disease progression is slower.