Pooled Analysis Highlights Safety, Efficacy of Satralizumab for NMOSD

Zdenka Haskova, MD, PhD

A new analysis of safety and efficacy data from a pair of phase 3 trials is shedding new light about the potential of satralizumab for treatment of neuromyelitis optics spectrum disorder (NMOSD).

Scheduled to be presented at the 2020 Association for Research in Vision and Ophthalmology annual meeting, the analysis dives deeper into the results of the SAkuraSky and SAkuraSTAR trials to examine the efficacy and safety of satralizumab as a monotherapy, in combination with immunosuppressants, and in specific patient subgroups.

SAkuraSky enrolled 83 patients randomized in a 1:1 ratio to satralizumab 120 mg in combination with baseline immunosuppressants or placebo. In SAkuraStar, 95 patients were randomized in a 2:1 ratio to satralizumab 120 mg monotherapy or placebo.

The primary endpoint of the pooled analysis and both studies was time to first protocol-defined relapse (PDR).

In SAkuraSky, use of satralizumab was associated with a 62% (HR, 0.38; 95% CI, 0.16—0.88) reduction in PDR versus placebo and, in SAkuraStar, use was associated with a 55% (HR, 0.45; 95% CI, 0.23–0.89) reduction in PDR versus placebo (both P=.018). When examining impact among patients who were seropositive for aquaporin-4 immunoglobulin G (AQP4-IgG), satralizumab use was associated with a 79% reduction in risk for PDR in SAkuraSky (HR 0.21; 95% CI, 0.06—0.75) and a 74% reduction in risk in SAkuraStar (HR 0.26; 95% CI, 0.11–0.63).

Results of the pooled analysis indicated a 58% reduction in risk for time to first PDR among patients receiving satralizumab (HR 0.42; 95% CI, 0.25-0.71). Among AQP4-IgG-seropositive patients, satralizumab use was associated with a 75% risk reduction in time to first PDR.

Investigators also highlighted similar incidence of adverse events between the satralizumab and placebo groups during the trial. Additionally, there were no observed deaths or anaphylactic reactions in either trial.

In an effort to learn more about satralizumab, HCPLive® reached out to the study’s lead investigator Zdenka Haskova, MD, PhD, medical director of clinical ophthalmology at Genentech, to take part in a Q&A on the humanized recycling monoclonal antibody.

HCPLive: What do the results of the analysis, particularly the impact in AQP4-IgG—seropositive patients, tell us about satralizumab?

Haskova: This pooled analysis of data from the two randomized, double-masked Phase III trials with satralizumab in patients with neuromyelitis optica spectrum disorder (NMOSD), SAkuraSky and SAkuraStar, demonstrated the robust efficacy of satralizumab in reducing the risk of relapse in people with NMOSD. These effects were particularly pronounced in patients who were seropositive for aquaporin-4 antibodies (AQP4-IgG). Through the use of a diagnostic biomarker test, most people with NMOSD are identified as seropositive for AQP4-IgG antibodies and tend to experience a more severe disease course; approximately one-third of patients with NMOSD are AQP4-IgG seronegative. In AQP4-IgG seropositive patients, satralizumab achieved a 79% reduction in the risk of relapse in combination with baseline immunosuppressants (SAkuraSky; NCT02028884) and 74% reduction in the risk of relapse as a monotherapy (SAkuraStar; NCT02073279).

HCPLive: Can we learn anything about the safety profile of satralizumab when used as a monotherapy and in combination with immunosuppressants based on results of the current study?

Haskova: Safety data from the double-masked periods of the two pivotal Phase III studies show satralizumab was well-tolerated as a monotherapy or in combination with baseline immunosuppressive therapy in a broad patient population with NMOSD. Overall, the proportions of patients with adverse events and serious adverse events, including infections, were comparable between satralizumab and placebo groups.

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This study, “Efficacy and safety of satralizumab from two phase 3 trials in neuromyelitis optica spectrum disorder,” was scheduled to be presented at ARVO 2020.