Satralizumab Reduces Risk of Relapse, Including in Treatment-Naïve NMOSD

September 17, 2020

Two posters presented at MS 2020 confirm satralizumab’s ability to reduce protocol-defined relapse including in patients with treatment-naïve NMOSD.

Data from the open-label extension and a substudy of the SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279) trials revealed that patients with neuromyelitis optica spectrum disorder (NMOSD), whether they were treatment-naïve or not, had a reduced risk of relapse with treatment of satralizumab (Enspryng; Genentech).1,2

Both studies were presented at MS Virtual 2020, the 8th joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, and assessed protocol-defined relapse (PDR) in patients with NMOSD who were assigned to satralizumab.

The first of the 2 presentations used data from both the SAkura studies and their open-label extension periods. Among a cohort of 179 patients, patients originally randomized to satralizumab (n = 105) showed a 51% lower risk of investigator-reported PDR compared to those originally randomized to placebo (n = 74; hazard risk [HR], 0.49; 95% CI, 0.31–0.79; P = .002).

Led by Benjamin Greenberg, MD, pediatric neurologist, University of Texas Southwestern Medical Center, the study also showed that the risk reduction was more pronounced in aquaporin-4-IgG seropositive (AQP4-IgG+) patients with NMOSD (66% risk reduction; HR, 0.34; 95% CI, 0.19–0.62; P <.001).

There were no patients in the satralizumab group that withdrew during the open-label extension due to a relapse compared to 4 patients who were originally randomized to placebo. Additionally, the safety findings noted in the open-label extension were consistent to those found in the double-blind period.

Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, was also observed in a subgroup of 6 treatment-naïve, AQP4-IgG+ patients with NMOSD enrolled in SAkuraStar after their first attack. After their incident attack, treatment-naïve AQP4-IgG+ patients randomized to placebo (n = 2) experienced a relapse earlier than those randomized to satralizumab (n = 4). All patients fully recovered to pre-relapse Expanded Disability Status Scale (EDSS) score at the end of the trial period.

In total, 1 patient who received placebo experienced a PDR on study Day 21, and 2 of the 4 satralizumab patients experienced a relapse as well. The patient on placebo who experienced a PDR had a 1.5-point increase in EDSS score and was able to fully recover to pre-relapse EDSS score. As for the 2 on satralizumab, the first patient experienced a PDR on Day 214, with a 1-point increase in EDSS, and the second patient experienced a relapse (not meeting PDR criteria) on Day 458, with a 0.5-point increase in EDSS score. Both patients were able to fully recover to pre-relapse EDSS score. Investigators noted that interpretation of the study is limited due to the small sample size.

Satralizumab was approved for the treatment of adult patients with AQP4-IgG antibody positive NMOSD in August, becoming the third targeted treatment along with Alexion’s eculizumab (Soliris) and Viela Bio’s inebilizumab (Uplizna) for this population and the first eligible for at-home administration.3

The approval was based off both SAkura studies, which combined included more than 170 patients who were randomly assigned to received satralizumab 120 mg or placebo. In SAkuraSky, patients added treatment to baseline immunosuppressive therapy.

In SAkuraStar, 30% of patients treated with satralizumab monotherapy experienced relapse compared with 50% of those who received placebo (HR 0.45; 95% CI, 0.23—0.89; =.018).4 Among those who were AQP4-IgG antibody positive, a 74% reduction in relapse risk was observed. In the overall satralizumab-treated population, 76.1% and 72.1% were relapse-free at 48 and 96 weeks, respectively, compared with 61.9% and 51.2% with placebo. Data from the AQP4-IgG seropositive subgroup showed that 82.9% and 76.5% were relapse-free at 48 and 96 weeks compared with 55.4% and 41.1% with placebo, respectively.

In total, 92% (n = 58) of those in the satralizumab group experienced an adverse event compared with 75% (n = 24) of the placebo group. Serious AEs were similar between groups; only 1 event led to study drug discontinuation in the treatment group.

In SAkuraSky, 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% reduction in relapse risk (HR 0.21, 95% CI, 0.06-0.75; P =.0086).5 Results showed 88.9% and 77.6% of patients in the total population were relapse-free at 48 and 96 weeks, respectively, compared with 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. The most common AEs observed were upper respiratory tract infection, nasopharyngitis, and headache.

For more coverage from MS 2020, click here.

REFERENCES
1. Greenberg B, Bennett J, De Seze J, et al. Efficacy of satralizumab in neuromyelitis optica spectrum disorder (NMOSD): results from open-label extension periods of SAkuraSky and SAkuraStar. Presented at MDS Virtual Congress; September 12–16, 2020. Abstract P0711
2. Palace J, Bennett J, Stokmaier D, Von Budingen H, Klingelschmitt G, Traboulsee A. Satralizumab in first incident treatment-naïve AQP4-IgG seropositive NMOSD patients enrolled to SAkuraStar: a case series. Presented at MDS Virtual Congress; September 12–16, 2020. Abstract P0754.
3. FDA approves Genentech’s Enspryng for neuromyelitis optica spectrum disorder. News release. Genentech. August 14, 2020. Accessed September 15, 2020. https://www.businesswire.com/news/home/20200814005501/en/ADDING-MULTIMEDIA%C2%A0FDA-Approves-Genentech%E2%80%99s-Enspryng-Neuromyelitis-Optica
4. 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&shy;-412. doi: 10.1016/S1474-4422(20)30078-8
5. Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019; 381:2114-2124. doi:10.1056/NEJMoa1901747