Satralizumab Shows Potential in NMOSD With FDA Approval Pending

May 18, 2020

With an FDA decision on a BLA for the Genentech agent expected later this year, the Group Medical Director of Neuroscience at Genentech shared insight on recent findings of satralizumab in NMOSD.

Kathleen Hawker, MD

Recently published phase 3 data suggest that satralizumab (also known as SA237) effectively reduced the rate of relapse in patients with neuromyelitis optica spectrum disorder (NMOSD) compared with placebo, with a positive safety profile, when used as a monotherapy.

The study authors noted that the findings were suggestive of the Genentech agent’s potential to become a valuable option for those with NMOSD, a sentiment seemingly shared by the FDA, which granted satralizumab a breakthrough therapy designation for the treatment of NMOSD in December 2018. In October the following year, the agency accepted Genentech’s biologics license application (BLA) for satralizumab based on findings from its phase 3 trials that showed its effectiveness in reducing the risk of relapses in patients with NMOSD.

As the FDA is expected to make a decision later this year, and to inquire further about the findings of the SAkuraStar study, NeurologyLive reached out to Kathleen Hawker, MD, Group Medical Director of Neuroscience, Genentech, to gain her perspective.

NeurologyLive: What are the main takeaways from this assessment of satralizumab?

Kathleen Hawker, MD: The phase III SAkuraStar data published in The Lancet Neurology show satralizumab monotherapy demonstrated robust efficacy and a well-tolerated safety profile, sustained for 144 weeks, significantly reducing the risk of relapse compared with placebo in the overall trial population. In the overall population, only 19 of the 63 patients (30%) treated with satralizumab experienced a relapse compared to 16 of the 32 patients (50%) treated with placebo. 76.1% were relapse-free at 48 weeks, 72.1% relapse-free at 96 weeks, and 62.8% relapse-free at 144 weeks, compared to 61.9%, 51.2%, and 34.1% with placebo, respectively.

Data from the aquaporin-4 antibody (AQP4-IgG) seropositive subgroup showed that 82.9% were relapse-free at 48 weeks and 76.5% relapse-free at both 96 weeks and 144 weeks when treated with satralizumab, compared to 55.4% and 41.1% with placebo, respectively. Satralizumab achieved a 74% reduction in the risk of relapse in the larger subgroup of AQP4-IgG seropositive patients, who tend to experience a more severe disease course.

How do these data add to the existing literature on the agent?

The phase III SAkuraStar data were consistent with the reported efficacy and safety of satralizumab in combination with baseline immunosuppressants (SAkuraSky; NCT02028884), suggesting that satralizumab could be a valuable treatment option for patients with neuromyelitis optica spectrum disorder. Satralizumab has shown robust efficacy sustained for 144 weeks across a broad patient population in two phase 3 studies, whether given as a monotherapy or in combination with baseline therapy. The SAkuraSky and SAkuraStar studies represent one of the largest clinical trial programs for this rare disease, and both studies include AQP4-IgG seropositive and seronegative patients, reflective of a real-world population of adolescents and adults.

Were any of the findings surprising or unexpected in any way?

IL-6 is thought to be a key driver in NMOSD, triggering the inflammation cascade and leading to damage and disability. The positive phase III results for satralizumab, as both a monotherapy and in combination with baseline immunosuppressant therapy, reinforce that IL-6 inhibition may be an effective therapeutic approach for NMOSD. As an investigational monoclonal antibody that targets the IL-6 receptor, satralizumab may help block IL-6 signaling and therefore limit NMOSD disease activity.

Transcript edited for clarity.

REFERENCE

Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomized, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402­-412. doi: 10.1016/S1474-4422(20)30078-8