Roche's Anti-inflammatory Drug Satralizumab Achieves Positive Phase III Results, Reducing Relapse Risk by 55% in NMOSD

On September 12, Roche announced the results of the second pivotal Phase 3 clinical trial of its IL-6 antibody satralizumab for the treatment of neuromyelitis optica spectrum disorder (NMOSD) at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). As a monotherapy, satralizumab reduced the risk of disease relapse by 55%. At last year’s ECTRIMS, Roche had announced the results from SAkuraSky, the first pivotal Phase 3 trial of satralizumab. In December last year, the U.S. FDA granted breakthrough therapy designation to this therapy.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, disabling autoimmune disease of the central nervous system (CNS) that affects up to hundreds of thousands of people worldwide. The primary manifestations in patients are inflammatory lesions of the optic nerves and spinal cord. NMOSD is characterized by frequent relapses, and repeated immune-mediated attacks on self-tissues lead to progressive accumulation of neurological damage and disability. Patients experience declines in vision, motor function, and quality of life, and severe NMOSD attacks can be fatal. Currently, there are no approved therapies for this condition.

Although neuromyelitis optica spectrum disorder (NMOSD) is considered a disease caused by the entry of AQP4-IgG-targeting autoantibodies into the central nervous system (CNS), approximately one-third of patients do not have these autoantibodies. In recent years, the pro-inflammatory cytokine interleukin-6 (IL-6) has emerged as an important therapeutic target in the pathogenesis of NMOSD, triggering inflammatory cascades that lead to tissue damage and disability. Satralizumab, developed by Roche, is a fully humanized monoclonal antibody against IL-6. It inhibits the IL-6 signaling pathway, thereby suppressing inflammation and the production of AQP4-IgG-targeting autoantibodies. Administered via subcutaneous injection once every four weeks, satralizumab offers a convenient treatment option for patients and caregivers.

A total of 95 patients with neuromyelitis optica spectrum disorder (NMOSD) participated in the SAkuraStar double-blind, Phase 3 clinical trial, in which patients were randomized to receive either satralizumab or placebo. The primary endpoint was the time to first relapse after treatment initiation. Trial results demonstrated that, compared with the placebo group, patients receiving satralizumab monotherapy experienced a 55% reduction in the risk of relapse. The relapse-free rates at 96 weeks and 48 weeks were 76.1% and 72.1%, respectively, versus 61.9% and 51.2% in the placebo group. Furthermore, in the subgroup of patients who were seropositive for aquaporin-4 immunoglobulin G (AQP4-IgG), satralizumab monotherapy reduced the risk of relapse by 74%. The relapse-free rates at 96 weeks and 48 weeks in this subgroup were 76.5% and 82.9%, respectively, compared with 41.1% and 55.4% in the placebo group.

Results from the SAkura Sky study, the first pivotal Phase 3 trial announced last year, demonstrated that patients receiving satralizumab in combination with standard therapy had a 62% reduced risk of relapse compared to the placebo group. In the subgroup of patients who were AQP4-IgG seropositive, this reduction was 79%. Data from both the SAkura Star and SAkura Sky trials indicate that satralizumab may be an effective treatment option broadly applicable to patients with NMOSD, whether administered as monotherapy or in combination therapy. Furthermore, both trials demonstrated a safety profile comparable to that of the placebo group.

“Although the existence of NMOSD has been known for 125 years, its biological basis has only recently begun to be understood. The positive results from the SAkuraStar and SAkuraSky trials confirm the importance of IL-6, a pro-inflammatory cytokine, in this devastating disease,” said Dr. Sandra Horning, Chief Medical Officer and Head of Global Product Development at Roche. “We are very pleased with these trial results and look forward to working with regulatory authorities in the coming months to bring satralizumab to NMOSD patients as soon as possible.”

References:

[1] Roche’s satralizumab significantly reduced relapse risk in second positive phase III study for neuromyelitis optica spectrum, Retrieved September 12, 2019, from https://www.roche.com/media/releases/med-cor-2019-09-12b.htm

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