The humanized monoclonal antibody was particularly effective in patients who were seropositive for aquaporin-4 autoantibodies.
Jeffrey Bennett, MD, PhD
Phase 3 data from the SAkuraStar study (NCT02073279) of satralizumab for the treatment of neuromyelitis optica spectrum disorder (NMOSD) demonstrate a significantly reduced risk for relapse.
The pivotal results, presented at ECTRIMS 2019, September 11-13 in Stockholm, Sweden, support the efficacy and safety of the humanized monoclonal antibody monotherapy in patients in the general NMO population and those who are seropositive and seronegative for aquaporin-4 (AQP4) autoantibodies.
The phase 3, double-blind, placebo-controlled study included 95 patients who were randomly assigned 2:1 to either satralizumab 120 mg subcutaneously (n=63) or placebo (n=32) at weeks 0, 2, 4, and every 4 weeks thereafter. Patients were prohibited from taking concomitant immunosuppressive therapy, and had at least 1 documented relapse, including first attack, in the year prior to screening. The primary end point was time to first protocol-defined relapse.
Results shows a 55% reduction of relapse risk in patients treated with satralizumab monotherapy compared with placebo (hazard ratio [HR] 0.45; 95% CI, 0.23-0.89; P =.018). Ultimtealy, 30.2% of patients in the treatment group experienced a relapse compared with 50% of patients in the placebo group.
At week 48, 76.1% of patients in the treatment group were relapse-free compared to 61.9% in the placebo group. The results remained stable through week 96, with 72.1% in the treatment group documented as relapse free compared with 51.2% of those in the placebo group.
Notably, patients who were seronegative for AQP4 did not show as great of a degree of response as the seropositive cohort. In an interview with NeurologyLive, study co-author Jeffrey Bennett, MD, PhD, professor of neurology and ophthalmology at the University of Colorado, posited that the results in the seronegative population may be due to the study being underpowered, and “possibly because what we consider currently [to be] seronegative NMO is a different condition than what seropositive patients have. We already know from background studies in the field that many patients who have MOG-IgG disease may mimic NMO, and we currently don't know how many of those patients might have been enrolled in this study under the seronegative categories.”
The study drug was well-tolerated and demonstrated a similar safety profile compared with placebo. The rate of serious adverse events was similar between both groups, and no anaphylactic reactions or deaths were recorded.
“There were a surprising lack of injection-related adverse events,” Bennett commented. “As we've come to understand in the MS field, injectables often have a significant adverse event profile, so the fact that [satralizumab] lacks the signature of infection risk was a pleasant surprise.”
The drug, which received breakthrough therapy designation from the FDA in December 2018, may be the second player in the NMOSD space if it achieves regulatory approval. In June, the FDA approved eculizumab (Soliris; Alexion) for the treatment of AQP4-seropositive NMOSD.
“There's now been 2 separate studies with interleukin 6 receptor inhibition and both have been quite successful in reaching their primary outcome, which in this disease is the elimination of relapse,” Bennett said. “[The results] give us the opportunity to consider in patients who are on prior therapy as well as off prior therapy that the addition of this agent is going to have efficacy. The adverse event profile was quite low, and it gives [clinicians] the option that if a patient was getting some benefit from the prior therapy, they can get additional benefit from adding on this medication, or if they felt they had little to be gained or had significant side effects from their prior therapy, they could switch and feel comfortable with monotherapy.”
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Traboulsee A, Greenberg B, Bennett JL, et al. Efficacy and safety of satralizumab monotherapy for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD): results from SAkuraStar, a double-blind placebo-controlled Phase 3 clinical study. Presented at: ECTRIMS 2019. September 11-13, 2019; Stockholm, Sweden. Abstract P603.