12.02.19

Positive Phase 3 Results for Genentech’s Satralizumab in Neuromyelitis Optica Spectrum Disorder Published in NEJM

Source: Genentech

Genentech announced that data from SAkuraSky, a pivotal phase 3 study of the investigational medicine satralizumab for the treatment of neuromyelitis optica spectrum disorder (NMOSD), were published in the November 27, 2019 online issue of the New England Journal of Medicine (NEJM).

“The positive results from the pivotal SAkuraSky study of satralizumab support the hypothesis that IL-6 plays a key role in NMOSD, which is a debilitating and potentially fatal condition,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, said in a company news release. “Satralizumab has shown robust efficacy sustained for 144 weeks across a broad patient population in two phase 3 studies, whether given as a monotherapy or in combination with baseline therapy. We’re encouraged that satralizumab may soon provide a new treatment option for people living with NMOSD.”

People with NMOSD experience unpredictable, severe relapses that directly cause cumulative, permanent, neurological damage and disability. The condition is often misdiagnosed as multiple sclerosis. Satralizumab inhibits interleukin-6 (IL-6) signaling, which is believed to play a key role in the inflammation that occurs in people with NMOSD. Satralizumab can be self-administered every four weeks by subcutaneous injection.

Detailed results published in NEJM highlight that in the overall study population, only eight of 41 patients (20%) treated with satralizumab in combination with baseline immunosuppressant therapy experienced a protocol-defined relapse (PDR) compared to 18 of 42 patients (43%) treated with placebo in combination with baseline therapy (Hazard Ratio [HR]=0.38, 95% CI: 0.16-0.88; p=0.02). Importantly, 89%, 78% and 74% of patients on satralizumab in combination with baseline therapy were relapse-free at weeks 48, 96, and 144 compared to 66%, 59% and 49% with placebo in combination with baseline therapy. Notably, the intention-to-treat (ITT) population studied included both aquaporin-4 (AQP4-IgG) seropositive and seronegative patients, reflecting a real-world population of adolescents and adults (age 13-73 years) with NMOSD. People who are AQP4-IgG seropositive tend to experience a more severe disease course.

In the AQP4-IgG seropositive subgroup analysis, three of 27 patients (11%) treated with satralizumab experienced a PDR compared to 12 of 28 patients (43%) treated with placebo (HR=0.21, 95% CI: 0.06-0.75). In the AQP4-IgG seronegative subgroup analysis, five of 14 patients (36%) treated with satralizumab experienced a PDR compared to six of 14 patients (43%) receiving placebo (HR= 0.66, 95% CI: 0.20-2.24).

Overall, the proportion of patients with serious adverse events was similar between the satralizumab and placebo treatment groups. A lower rate of infections (including serious infections) was observed in patients treated with satralizumab compared with the placebo group. Most adverse events were mild to moderate, and the most common adverse events in the satralizumab group were upper respiratory tract infection, nasopharyngitis (common cold) and headache.

In October 2019, the FDA accepted the Biologics License Application (BLA) for satralizumab for the treatment of NMOSD. The FDA is expected to make a decision on approval in 2020.

About the SAkuraSky study in NMOSD

SAkuraSky is a Phase III multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of satralizumab added to baseline immunosuppressant therapy in patients with NMOSD. The primary endpoint was the time to first relapse as adjudicated by an independent review committee in the double-blind period.

Eighty-three male and female patients 13-73 years of age were randomized to either of the following two treatment groups in a 1:1 ratio: satralizumab (120 mg) or placebo added to baseline therapy (azathioprine, mycophenolate mofetil and/or corticosteroids). Both treatments were administered subcutaneously at Week 0, 2 and 4. The subsequent treatment was continued at 4-week intervals. The double-blind treatment ended when patients experienced a PDR; the study ended when the total number of PDRs reached 26. After experiencing a PDR or upon completion of the study, patients in both groups were offered treatment with satralizumab in an open-label extension period. Patients with AQP4-IgG seropositive or seronegative neuromyelitis optica (NMO, as defined by the diagnostic criteria in 2006) and those with AQP4-IgG seropositive NMOSD were enrolled.

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