Genentech presented full pivotal phase 3 study results for satralizumab as a monotherapy for neuromyelitis optica spectrum disorder (NMOSD), a rare, debilitating central nervous system disease. Results from the SAkuraStar study, presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), show that satralizumab monotherapy achieved a 55% reduction in the risk of relapses compared to placebo in the overall population, representative of NMOSD patients (Hazard Ratio [HR]=0.45, 95% Confidence Interval [CI]: 0.23-0.89; p=0.0184). In the large (~67%) subgroup of patients seropositive for AQP4-IgG antibodies, the effect was higher with a 74% reduction in risk of relapses (HR=0.26, 95% CI: 0.11-0.63; p=0.0014). People who are AQP4-IgG seropositive tend to experience a more severe disease course.
“The positive phase 3 results for satralizumab, first as an add-on therapy and now as a monotherapy, are exciting to see, and importantly, satralizumab achieved efficacy in a broad range of NMOSD patients, reflective of what we see in our everyday practice. Satralizumab targets the IL-6 receptor, potentially offering a novel treatment approach,” Professor Jeffrey Bennett, University of Colorado Neurology & Ophthalmology, said in a company news release. “Approved treatment options demonstrating favorable safety and efficacy in controlled clinical trials are urgently needed. Even one relapse may lead to blindness and debilitating motor dysfunction for people with NMOSD.”
In the overall satralizumab-treated population, 76.1% were relapse-free at 48 weeks, and 72.1% relapse-free at 96 weeks, compared to 61.9% and 51.2% with placebo, respectively. Data from the AQP4-IgG seropositive subgroup showed that 82.9% were relapse-free at 48 weeks and 76.5% relapse-free at 96 weeks when treated with satralizumab, compared to 55.4% and 41.1% with placebo, respectively.
NMOSD is commonly associated with pathogenic antibodies (AQP4-IgG) that target and damage a specific cell type, called astrocytes, resulting in inflammatory lesions of the optic nerve(s), spinal cord, and brain. Through the use of a diagnostic biomarker test, most NMOSD patients are identified as AQP4-IgG seropositive; however, as many as one-third of patients with NMOSD are AQP4-IgG seronegative. The condition is often misdiagnosed as multiple sclerosis.
Satralizumab inhibits IL-6 signaling, which is believed to play a key role in the inflammation that occurs in people with NMOSD, leading to damage and disability. People with NMOSD experience unpredictable, severe relapses that directly cause cumulative, permanent neurological damage.
“While first described 125 years ago, the underlying biology of NMOSD has only recently been understood. The positive results from the pivotal SAkuraStar and SAkuraSky studies support the hypothesis that IL-6 plays a key role in this devastating disease that can take away people’s independence,” Sandra Horning, MD, chief medical officer and head of Global Product Development, said in the news release. “We are encouraged by these results and look forward to working with regulators over the coming months to bring satralizumab to people living with NMOSD as soon as possible.”
These SAkuraStar data add to the previously reported results for satralizumab in combination with baseline therapy for people with NMOSD. Initial phase 3 data for SAkuraSky were presented at the 34th ECTRIMS Congress in 2018. The data showed a 62% reduction in the risk of relapses in a representative population of both AQP4-IgG seropositive and AQP4-IgG seronegative patients in the overall study population (HR=0.38, 95% CI: 0.16-0.88; P=0.0184) when used in combination with baseline therapy compared to placebo, and a 79% reduction in the risk of relapses in AQP4-IgG seropositive patients (HR=0.21, 95% CI: 0.06-0.75; P=0.0086).
Overall, the proportion of patients with serious adverse events was similar between the satralizumab monotherapy and placebo treatment groups in the SAkuraStar study; and between the satralizumab added to baseline therapy and placebo added to baseline therapy treatment groups in the SAkuraSky study. A lower rate of infections (including serious infections) was observed in patients treated with satralizumab compared with the placebo group. In both studies, most adverse events were mild to moderate, and the most common adverse events in the satralizumab group were urinary tract infections and upper respiratory tract infections in the SAkuraStar study and upper respiratory tract infection, nasopharyngitis (common cold) and headache in the SAkuraSky study. Safety analyses continue in the open-label extensions of SAkuraStar and SAkuraSky.
The data available across two controlled, randomized phase 3 clinical trials suggest that satralizumab could be an efficacious option for a broad NMOSD patient population, whether given as a monotherapy or in combination with baseline therapy. Satralizumab is administered every four weeks by subcutaneous injection, which may be a convenient option for patients and caregivers.
The SAkuraStar study recruited 95 NMOSD patients aged 20-70 and SAkuraSky recruited 83 patients, including adolescents, aged 13-73. These studies represent one of the largest clinical trial programs undertaken for this rare disease.