The data from the SAkuraStar study on satralizumab add to the total literature on the Genentech humanized monoclonal antibody, which is set for FDA decision later this year.
Anthony Traboulsee, MD
Recently published phase 3 data suggest that satralizumab (also known as SA237) as monotherapy effectively reduced the rate of relapse in patients with neuromyelitis optica spectrum disorder (NMOSD) compared with placebo, with a positive safety profile.
The SAkuraStar study (NCT02073279) authors, including Anthony Traboulsee, MD, professor and Research Chair, MS Society of Canada, University of British Columbia (UBC), and director, MS/NMO Clinic and Clinical Trials Research Group, UBC Hospital, noted that the study population (n = 95) included a ratio of aquaporin-4 (AQP4-IgG) antibody seropositive and seronegative patients, reflective of clinical practice, suggesting that the Genentech agent has the potential to become a valuable option for those with NMOSD.
All told, those treated with satralizumab (n = 63) reported protocol-defined relapses, as adjudicated by the Clinical Endpoint Committee (CEC), at a rate of 30% (n = 19) compared to a rate of 50% (n = 16) of those in the placebo group (n = 32), equaling a hazard ratio (HR) of 0.45 (95% CI, 0.23—0.89; P = .018).
“These results were consistent with the reported efficacy and safety of satralizumab in combination with baseline immunosuppressants (SAkuraSky), suggesting that satralizumab could be a valuable treatment option for patients with NMOSD,” Traboulsee and colleagues wrote. “The ongoing extension studies will offer further insight into long-term safety and effectiveness of satralizumab in this disorder.”
As for safety, there were 473.9 adverse events (AEs; 95% CI, 435.0—515.4) per 100 patient-years which occurred in the satralizumab group (115.2 total patient-years), and 495.2 AEs (429.1–568.6) per 100 patient-years in the placebo group (40.6 total patient-years). In total 92% (n = 58) of those in the satralizumab group experienced an AE compared to 75% (n = 24) of the placebo group.
Serious AEs occurred in 19% (n = 12) of the satralizumab group and 16% (n = 5) of the placebo group. The incidence of serious AEs (satralizumab: 17.4 events per 100 patient-years [95%CI, 10.6—26.8; placebo: 14.8 events per 100-patient years [95% CI, 5.4–32.2]) was similar between groups. None of the severe AEs led to discontinuation of the study drug except for 1 severe event of pneumonia in the satralizumab group.
Participants were eligible for the SAkuraStar study if they’d experienced ≥1 documented NMOSD attack or relapse in the past year and had a score of ≤6.5 on the Expanded Disability Status Scale (EDSS). Participants were randomly assigned in 2:1 fashion to receive satralizumab 120 mg or visually matched placebo subcutaneously at Weeks 0, 2, 4, and every 4 weeks thereafter. Taking immunosuppressants concomitantly was prohibited.
In October 2019, the FDA 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. The agency is expected to make a decision later this year. Satralizumab was also previously granted breakthrough therapy designation for the treatment of NMOSD in December 2018.
Previously published data from SakuraStar that assessed satralizumab over 96 weeks showed that overall, 76.1% of patients assigned to satralizumab monotherapy were relapse-free at 48 weeks, compared to 61.9% who received placebo. At 96 weeks, 72.1% of patients who received treatment with satralizumab were relapse-free, compared with 51.2% of patients in the placebo group.2
Additionally, the total population of AQP4-IgG seropositive and seronegative patients assigned to satralizumab monotherapy saw a 55% decrease in the risk of relapse compared to placebo (HR, 0.45 [95% CI, 0.23—0.89]; P =.0184). Notably, the larger subgroup of seropositive patients, who experience a more severe disease course, saw a reduction in risk of relapses of 74% (HR, 0.26 [95% CI, 0.11—0.63]; P =.0014).
In SAkuraSky (NCT02028884), another assessment in satralizumab’s development reported the risk of relapses with treatment with satralizumab compared to placebo in combination with immunosuppressant therapy. In that study, the overall population saw a 62% reduction in the risk of relapse (HR, 0.38 [95% CI, 0.16—0.88]; P =.0184), while the group of AQP4-IgG seropositive patients experienced a 79% relapse risk reduction (HR, 0.21 [95% CI, 0.06—0.75]; P =.0086). Results showed 88.9% and 77.6% of patients in the total population were relapse-free at 48 and 96 weeks, respectively, compared to 66% and 58.7% of patients in the placebo group. Among AQP4-IgG seropositive patients, 91.5% treated with satralizumab were relapse-free at 48 and 96 weeks, compared with 59.9% and 53.3% of patients in the placebo group.2
1. 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
2. FDA Accepts Genentech’s Biologics License Application for Satralizumab for Neuromyelitis Optica Spectrum Disorder [news release]. San Francisco, CA: Genentech; Published October 29, 2019. Accessed May 13, 2020. biospace.com/article/releases/fda-accepts-genentech-s-biologics-license-application-for-satralizumab-for-neuromyelitis-optica-spectrum-disorder.