PHILADELPHIA – , according to results presented at the annual meeting of the American Academy of Neurology. The antibody also reduces the risks of disability worsening, MRI lesion activity, and hospitalization.
No approved therapies are available for NMOSD, which is thought to be a B-cell-mediated disorder. Research suggests that CD19 is a potential therapeutic target in NMOSD. Inebilizumab has a high affinity for CD19 and reliably depleted B cells in preclinical and clinical studies.
Participants did not receive concomitant immunosuppressants
Bruce Cree, MD, PhD, clinical research director at the University of California, San Francisco, Multiple Sclerosis Center, and colleagues conducted a phase 3 study to evaluate the safety and efficacy of inebilizumab in NMOSD. Eligible participants were older than 18 years, had NMOSD, and were seropositive for aquaporin-4 (AQP4) antibodies. Seronegative patients were allowed to participate, provided that they met the 2006 Wingerchuk criteria for neuromyelitis optica. Participants were required to have had one attack in the previous year or two attacks in the 2 previous years. Participants had a wide range of disability. No background use of immune suppressants was permitted.
The trial was conducted at 99 centers in 24 countries. After a 4-week screening period, investigators randomized patients in a 3:1 ratio to inebilizumab or placebo. Treatment was administered on days 1 and 15 by IV infusion. The randomized, controlled period lasted for 197 days. If a participant did not have a relapse by the end of this period, he or she was given the choice of participating in a yearlong open-label study, in which he or she would receive 300 mg of inebilizumab every 6 months. Participants who had an attack were treated for the attack.
An independent eligibility committee reviewed and confirmed the diagnostic criteria for AQP4 seronegative participants. A masked attack-adjudication committee provided real-time assessment of NMOSD attacks. An independent data monitoring committee reviewed patient safety and ensured the ethical conduct of the study.
The trial’s primary endpoint was the time from randomization to first attack. Secondary endpoints included a measure of disability, a measure of visual acuity, cumulative lesions on MRI, and NMOSD-related inpatient hospitalizations.
Treatment reduced the risk of hospitalization
Dr. Cree and colleagues screened 467 subjects and randomized 231. Among those patients, 175 received inebilizumab, and 56 received placebo. The population’s mean age was 43 years. About 90% were women, and 72% were white or Asian. The median baseline disability score was 3.5, indicating moderate disability. More than 90% of patients were AQP4 seropositive. The mean number of attacks at entry was 4.3. About 60% of participants had had prior exposure to immune suppressants.
Enrollment into the randomized, controlled period was stopped at 231 patients after 43 attacks had occurred, based on the recommendation of the independent data monitoring committee, which concluded that further recruitment into the placebo arm would not be ethical. The committee also recommended that all participants be shifted into the open-label period.
Among AQP4 seropositive patients, 88% of the inebilizumab group did not have an attack, compared with 57% of the control group. This result represents a 77% reduction in the risk of a relapse following inebilizumab treatment. The number needed to treat was 3.23. In the population overall, 87% of patients treated with inebilizumab did not have an attack, compared with 60% of controls, which corresponded to a 73% reduction in risk of an attack and a number needed to treat of 3.7.
In addition, Dr. Cree and colleagues found that inebilizumab was associated with a 63% reduction in risk of disability, a 43% reduction in risk of developing new lesions, and a 71% reduction in NMOSD-related hospitalizations. These results were statistically significant and clinically meaningful, he said. The only secondary endpoint that was not met was the difference in binocular low-contrast visual acuity scores. “This [result] may be due to the low frequency of optic neuritis events, a floor effect within the placebo arm (many of those patients had profound visual loss at baseline), or selection of a binocular acuity test that diluted the impact of monocular events,” said Dr. Cree.
Adverse events and serious adverse events were well balanced between the two treatment arms. The rate of infusion-related reactions was low in both arms and was “perhaps slightly lower in the inebilizumab treatment arm,” said Dr. Cree. No deaths occurred during the randomized, controlled period, and the researchers found no pattern of serious adverse events. Two deaths occurred in the open-label period: one related to a severe attack, and the other related to a brain event of unclear etiology without definite diagnosis.
B cells were depleted within approximately 4 weeks of treatment, and this depletion was sustained throughout the randomized, controlled period.
This study was funded by Viela Bio and MedImmune. Dr. Cree has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.
SOURCE: Cree B et al. AAN 2019. Abstract Plen02.001.