STOCKHOLM — Satralizumab, a humanized recycling monoclonal antibody in development, is promising for reducing risk of relapses in patients with autoimmune neuromyelitis optica spectrum disorder (NMOSD), new research suggests.
In a follow-up to the SAkuraSky double blind, phase 3 study that evaluated satralizumab as an add-on therapy, investigators compared antibody monotherapy efficacy vs placebo in another 95 patients with NMOSD in the SAkuraStar study.
The current findings showed a 55% risk reduction in time to first relapse compared with placebo, the primary endpoint of the trial.
"This is a disease based on attacks, and you're doing well before you're not," lead author Jeffrey L. Bennett, MD, PhD, professor of neurology and ophthalmology at the University of Colorado School of Medicine in Aurora, told Medscape Medical News.
"As investigators and clinicians, we will have to look at what is best for patients — as to whether concurrent therapy is better than monotherapy in the early phase of the disease," Bennett added.
He presented the results here at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019.
NMOSD is a rare and debilitating autoimmune disease of the central nervous system that can affect the optic nerves, brain stem, spinal cord, and brain. Previous research has shown that interleukin-6 levels correlate with disease activity. Satralizumab targets the IL-6 receptor; and researchers propose that inhibiting the IL-6 signaling in these patients could lead to less frequent and less severe relapses.
To learn more, Bennett and colleagues evaluated patients with NMOSD who were randomly assigned to receive either satralizumab 120 mg subcutaneous injection (n = 63) or placebo (n = 32). During an open label extension, all 95 participants received the monoclonal antibody.
The investigators predefined relapses based on new or worsening neurologic symptoms persisting for 24 hours or longer that were not attributable to other factors.
Demographics were similar between the groups, except for a mean age of 45 years in the satralizumab group vs 40 years in the placebo cohort. In addition, women accounted for 73% and 97% of the groups, respectively. Bennett noted these differences did not affect the study findings.
The participants experienced at least one relapse in the year prior to entry into the study.
Reduced Relapse Risk
In the overall population, satralizumab reduced relapse risk compared with placebo (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.23 - 0.89; P = .018).
The investigators also classified patients according to aquaporin-4 (AQP4-IgG) status. They reported that the active medication was particularly effective in reducing relapse risk among the 64 seropositive patients in the study — a 74% reduction compared with placebo (HR, 0.26; 95% CI, 0.11 - 0.63).
In addition, 83% of the seropositive patients were relapse-free at 48 weeks, as were 77% at week 96.
By comparison, only 55% and 41% of the seropositive placebo group were relapse-free at the same time points, respectively.
In contrast to the seropositive group findings, no benefit emerged among the 31 aquaporin-4 seronegative patients in terms of relapse risk reduction (HR, 1.19; 95% CI, 0.30 - 4.78).
Among the seronegative patients, relapse-free rates were the same at 48 weeks, at 63% of each treatment group. At 96 weeks, the rates were again the same, at 78% each.
It is unknown if the seronegative findings are related to a lack of efficacy because of statistical power or inclusion of mimics of aquaporin-4 positive disease, Bennett said. It would be helpful to know "if we are dealing with biology or numbers," he added.
Satralizumab also showed greater efficacy among 12 patients previously treated with B-cell depleting therapy in the study. The HR for risk of relapse in this group was 0.72 (95% CI, 0.12 - 4.30) compared with the placebo group.
When investigators looked at the 83 people previously treated with immunosuppressants or other NMOSD therapies, they found that satralizumab was associated with a 58% risk reduction compared with placebo (HR, 0.42; 95% CI, 0.20 - 0.87).
Relapse history made a difference in outcomes as well. The 84 participants with more than one relapse in the year prior to screening for the SAkuraStar study had a 58% risk reduction with the active treatment vs placebo (HR, 0.42; 95% CI, 0.21 - 0.85). However, the 11 people with only one relapse at the same time had no change in risk (HR, 1.00; 95% CI, 0.09 - 11.02).
The side effect profile of satralizumab showed no tolerance issues in the SAkuraSky and SAkuraStar studies, Bennett said. The rate of severe adverse events (AEs) that required hospitalization were not significantly different between groups and there were no deaths, he added.
However, there were more AEs rated as serious by investigators in the satralizumab group than in the placebo group (12 vs 5, respectively).
Bennett noted that the frequency of serious AEs decreased over time in the extension phase of the study and there was no particular distribution among organ classes.
Relative Efficacy Questioned
Asked to comment by Medscape Medical News, session comoderator Samia J. Khoury, MD, director of the Abu Haidar Neuroscience Institute and associate dean for clinical and translational research at the American University of Beirut, Lebanon, said that this study "addresses an important question" — to distinguish the role of satralizumab as add-on therapy vs monotherapy.
Khoury noted that the lack of significant efficacy among AQP4-IgG-seronegative patients leaves the unanswered question: Were these patients misdiagnosed with NMOSD or were they positive for a different antibody, such as anti-myelin oligodendrocyte glycoprotein (MOG)?
Overall, satralizumab "doesn't look as good as some other agents in terms of effectiveness, in my opinion," she added.
When asked to reply, Bennett said it is difficult to do an "apples-to-apples comparison" among the clinical trial results. The PREVENT trial, for example, only included aquaporin-4 positive patients and ended at 24 weeks compared with an endpoint of 1.5 years in the current study.
Bennett added that the overall news is good for all three agents — eculizumab (Soliris, Alexion), which is already approved in the US; satralizumab; and inebilizumab, both of which are currently in development.
Despite different therapeutic targets, each is demonstrating promising efficacy, he said. "It's rare that you get three shots at a goal and you score on all three."
The study was funded by F. Hoffmann-La Roche . Bennett is a consultant for Roche and Genentech and served on the steering committee for Chugai Pharma related to the SAkuraStar study. Khoury has disclosed no relevant financial relationships.
35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019: Abstract 141. Presented September 12, 2019.
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Cite this: Antibody Monotherapy Shows Promise in Neuromyelitis Optica - Medscape - Sep 12, 2019.