Background

Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced patients’ risk of NMOSD relapse in the double-blind (DB) periods of two randomized, phase 3 clinical trials in NMOSD: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To assess the efficacy of satralizumab over a longer period of treatment, using data from the SAkura studies’ open-label extension (OLE) periods.

Methods

Patients entering SAkuraSky/Star were randomized to receive satralizumab 120mg or placebo at Weeks 0, 2, 4, and Q4W thereafter. After completing the DB period or experiencing a relapse, patients could enter the OLE period (same satralizumab dosing as DB period). The primary endpoint of both studies was time to first protocol-defined relapse (PDR) in the DB period, adjudicated by a Clinical Endpoint Committee (CEC). In this analysis, which includes OLE data (CEC adjudication unavailable), we assessed time to first investigator-reported PDR (any relapse considered by the investigator to meet PDR criteria) in the combined DB+OLE periods, using a pooled population from both studies.

Results

Overall, 179 patients were randomized to treatment (satralizumab n=105; placebo n=74), of whom 166 received ≥1 dose of satralizumab in the combined DB+OLE period. The median (range) satralizumab exposure in the DB period was 96.1 (8–224) weeks, and in the combined DB+OLE was 131.9 (13–276) weeks.

In the combined DB+OLE, patients originally randomized to satralizumab had a 51% lower risk of investigator-reported PDR vs those originally randomized to placebo (HR [95% CI] 0.49 [0.31–0.79]; P=0.002); the risk reduction was more pronounced in AQP4-IgG seropositive patients (66% risk reduction; HR [95% CI] 0.34 [0.19–0.62]; P<0.001). Patients who switched from placebo to satralizumab upon entry into the OLE period were included in the placebo group for this analysis, which likely reduced the observed treatment difference between satralizumab and placebo compared with the DB period.

No patients randomized to satralizumab withdrew from the OLE period due to a relapse, vs four patients who were originally randomized to placebo. The safety profile of satralizumab in the OLE was consistent with the DB period.

Conclusions

Across the DB and OLE periods of the SAkura studies, patients randomized to satralizumab had a significantly reduced risk of relapse vs placebo.

Background

NMOSD is a chronic, auto-immune disease characterized by acute relapses that lead to accumulating disability. Satralizumab, a humanized, monoclonal antibody that inhibits the interleukin-6 receptor, reduced relapse frequency and had a favourable safety profile in two randomized, phase 3 clinical trials: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To assess the impact of satralizumab on infection risk in patients with NMOSD.

Methods

Infections and serious infections (those meeting serious adverse event [AE] criteria) in the double-blind (DB: satralizumab 120mg Q4W vs placebo) and open-label extension (OLE: satralizumab 120mg Q4W) periods of SAkuraSky and SAkuraStar were evaluated (data cut 7 Jun 2019). Exposure-adjusted rates (events per 100 patient-years [PY] of exposure) were assessed, as the total exposure time in the DB period was longer for satralizumab than placebo.

Results

Overall, 180 patients were included. In the DB period, infection rates [95% CI] were lower with satralizumab vs placebo in SAkuraStar (99.8 [82.4–119.8] vs 162.6 [125.8–206.9] events/100PY); there was no between-group difference in infection rates in SAkuraSky (satralizumab: 132.5 [108.2–160.5]; placebo: 149.6 [120.1–184.1] events/100PY). Serious infection rates were comparable between satralizumab and placebo in both studies (SAkuraSky: 2.6 [0.3–9.2] vs 5.0 [1.0–14.7] events/100PY, respectively; SAkuraStar: 5.2 [1.9–11.3] vs 9.9 [2.7–25.2] events/100PY, respectively). In both studies, the most common infections in both treatment groups were upper respiratory tract infections and urinary tract infections.

In the combined DB/OLE period (all patients receiving ≥1 dose of satralizumab; n=166; median [range] exposure: 184 [4–276] weeks in SAkuraSky; 122 [5–243] weeks in SAkuraStar), infection and serious infection rates were similar to the DB period (SAkuraSky: 134.5 [119.5–150.8] infections/100PY, 4.1 [1.9–7.8] serious infections/100PY; SAkuraStar: 90.6 [78.4–104.0] infections/100PY, 3.6 [1.6–7.2] serious infections/100PY). The rates of infections and serious infections did not increase over time. There were no cases of progressive multifocal leukoencephalopathy in either study.

Conclusions

There was no increased risk of infection or serious infection observed in patients treated with satralizumab vs placebo in the DB and OLE periods of the SAkura studies.

Background

Interleukin-6 (IL-6) is implicated in the immunopathology of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab, a humanized recycling monoclonal antibody that inhibits the IL-6 receptor, demonstrated a reduction in NMOSD relapse risk in two phase 3 studies: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To evaluate the safety of satralizumab vs placebo in a pooled population of NMOSD patients from the SAkura studies, including the latest data from the open-label extension (OLE) period of the studies.

Methods

SAkuraStar and SAkuraSky are randomized studies comprising a double-blind (DB) period (satralizumab 120mg Q4W vs placebo) followed by an OLE period (satralizumab only). The combined DB and extension period was defined as the overall satralizumab treatment (OST) period (cut-off: 7 Jun 2019). Safety was evaluated in the DB and OST periods and reported as adverse event (AE) rates per 100 patient-years (PY).

Results

The pooled DB population included 178 patients (satralizumab, n=104; placebo, n=74), and 166 patients received satralizumab in the OST. Median duration of safety observation with satralizumab was 96.1 weeks in the DB period and 131.9 weeks in the OST period. Rates of AEs and serious AEs were comparable between satralizumab and placebo groups in the DB period (AEs: 478.49 vs 506.51 events/100PY, respectively; serious AEs: 14.97 vs 17.98 events/100PY, respectively), and were consistent in the OST period. In the DB period, four patients (3.8%) in the satralizumab group and five (6.8%) in the placebo group discontinued treatment due to AEs. Serious infection rates were comparable between the satralizumab and placebo groups in the DB period (4.13 vs 6.99 events/100PY) and remained stable in the OST (3.88 events/100PY). No opportunistic infections were observed in the satralizumab group. The injection-related reaction (IRR) rate was higher with satralizumab vs placebo in the DB period (17.03 vs 8.99 events/100PY); IRRs were mostly mild-to-moderate and did not lead to treatment discontinuation. Laboratory abnormalities were in line with those expected with IL-6 receptor antagonists in the DB and OST period. No deaths or anaphylactic reactions were reported.

Conclusions

In NMOSD patients, satralizumab was well tolerated and showed a favorable safety profile. Results from the OST period were consistent with the DB period.