The U.S. Food and Drug Administration (FDA) has accepted Genentech’s Biologics License Application (BLA) for satralizumab to treat adults and adolescents with neuromyelitis optica spectrum disorder (NMOSD). The FDA’s review will largely focus on two Phase III studies testing the safety and efficacy of the drug on its own and in combination with standard autoimmune therapy. A decision is expected in 2020.
NMOSD is a rare autoimmune disease of the central nervous system that mostly damages the optic nerves and spinal cord that can cause blindness, muscle weakness and paralysis. Approximately 15,000 people in the United States are afflicted with NMODS and it is most common among non-Caucasian women in their 30s and 40s.
People with NMOSD are often misdiagnosed as having multiple sclerosis since the two disorders have overlapping characteristics, including a higher prevalence in women, similar symptoms, and conditions often relapse.
Satralizumab is a monoclonal antibody that targets the interleukin-6 (IL-6) receptor. The cytokine IL-6 is believed to be a key driver of NMOSD pathophysiology.
The FDA will review two Phase III studies involiving satralizumab to treat individuals with NMOSD – SAkuraStar and SAkuraSky.
The SAkuraStar study was a Phase III multicenter, randomized, double-blind, placebo-controlled study testing satralizumab monotherapy. The primary endpoint was the time to first protocol-defined relapse (PDR).Ninety-five adults with NMOSD were randomized (2:1 ratio) to receive satralizumab (120 mg) or placebo. The double-blind treatment period ended when the total number of PDRs had reached 44 or at 1.5 years after the enrollment of the last patient, whichever occurred first.
At the end of the study, the satralizumab monotherapy group achieved a statistically significant reduction (55%) in the risk of relapses compared to placebo in the overall study population of aquaporin-4 antibody (AQP4-IgG) seropositive and seronegative patients (P = .0184). Those with more severe symptoms showed a 74% reduction.
The SAkuraSky istudy was a Phase III multicenter, randomized, double-blind, placebo-controlled study comparing satralizumab plus baseline immunosuppressant therapy to immunosuppressant therapy alone in patients with NMOSD. The primary endpoint was the time to first relapse. A total of 83 teens and adults (ages 13 – 73 years) were randomized (1:1 ratio) to satralizumab (120 mg) or placebo in addition to baseline immunosuppressant therapy (azathioprine, mycophenolate mofetil and/or corticosteroids).
The SAkuraSky study showed a 62% reduction in the risk of relapses compared to placebo in the overall study population (P = .0184) when used in combination with baseline immunosuppressant therapy, and a 79% reduction in the risk of relapses in AQP4-IgG seropositive patients (P = .0086). In the overall satralizumab-treated population, 88.9% were relapse-free at 48 weeks, and 77.6% were relapse-free at 96 weeks, compared to 66.0% and 58.7% with placebo, respectively.
Most adverse events were mild to moderate, and the most common adverse events in the satralizumab group were urinary tract infection and upper respiratory tract infection in the SAkuraStar study and upper respiratory tract infection, nasopharyngitis and headache in the SAkuraSky study.
In a news release, Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development said, “People living with NMOSD experience unpredictable relapses that can cause permanent neurological damage, and although there have been significant strides recently in understanding the disease, more approved options are needed with different treatment approaches. Satralizumab has shown robust efficacy sustained for 96 weeks and significantly reduced the risk of relapse across a broad patient population, while offering self-administered subcutaneous dosing every four weeks.”