A phase 3 trial of eculizumab found the drug reduced the frequency of relapse neuromyelitis optica spectrum disorder (NMOSD), an autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord.
A phase 3 trial of eculizumab found the drug reduced the frequency of relapse neuromyelitis optica spectrum disorder (NMOSD), an autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord.
Results were published recently in The New England Journal of Medicine and discussed last week at the 2019 American Academy of Neurology Annual Meeting, May 4-10, 2019 in Philadelphia.
Eculizumab (Soliris) is a particularly high-cost biologic that treats rare and ultra-rare diseases, and that faces upcoming biosimilar competition from products in development by numerous manufacturers.
The study was funded by Alexion Pharmaceuticals, which makes the innovator product Soliris; in a statement, the company said the FDA is reviewing the drug under priority review and set a Prescription Drug User Fee Act (PDUFA) action date of June 28, 2019. The drug is also under review by the European Medicines Agency and the Japanese Pharmaceuticals and Medical Devices Agency for this indication.
Most cases of NMOSD are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. It affects mostly women and the prevalence is about 0.5 to 10 persons (predominantly women) per 100,000.
Immunosuppressive drugs, such as rituximab, are used off-label to prevent relapses in NMOSD, but 25% to 60% of patients receiving these medications continue to have recurrent attacks, which are frequently associated with complications such as blindness, paralysis, or even death. There is no currently approved treatment for NMOSD.
The randomized, double-blind, time-to-event trial took place at 70 sites in 18 countries. It assigned 143 adults in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first 4 doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or a matched placebo.
The continued use of stable-dose immunosuppressive therapy was permitted, except for rituximab, because of a conflict between its mechanism of action and that of the terminal complement inhibitor in eculizumab.
The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death).
The trial was stopped after 23 of the 24 prespecified adjudicated relapses, as decided by an independent panel, given that it wasn’t known when the last event would occur.
The patients who completed the trial could enter an extension trial and receive open-label treatment with eculizumab.
The mean (SD) annualized relapse rate in the 24 months before enrollment was 1.99 (0.94); 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02-0.20; P <.001).
The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01-0.15; P <.001).
The mean change in the EDSS score was —0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, –0.29; 95% CI, –0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was 1 death from pulmonary empyema in the eculizumab group.
The researchers say there was no significant between-group difference in measures of disability progression.
The study had several limitations, according to the researchers. Among them, since only patients with AQP4-IgG antibodies were included, the findings cannot be generalized to patients without AQP4-IgG antibodies. In addition, no formal inferences could be made about other disability and quality-of-life outcomes overall, because the trial design precluded follow-up beyond 6 weeks after a single relapse and because the confidence interval for the between-group difference in the change from baseline in the EDSS score included zero in hierarchical testing, which implies there was no benefit of the drug on disability progression during the short trial. In addition, treating physicians identified more relapses than the adjudication committee.
However, the study said that was mostly due “to the interpretation of the objective change in the neurologic examination, which we assessed as reflecting concern among treating physicians that relapses should not be overlooked.”
Despite that, the study “a significantly lower risk of relapse with eculizumab than with placebo was apparent in the sensitivity analysis of physician-determined relapses.”
Reference
Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4—positive neuromyelitis optica spectrum disorder [published online May 3, 2019]. NEJM. doi: 10.1056/NEJMoa1900866.
What Clinicians Need to Know About Using Biosimilars to Treat IBD
April 13th 2024A review article, intended to act as a guide for clinicians, summarizes the available infliximab and adalimumab biosimilars for treating inflammatory bowel disease (IBD) as well as others that are coming down the pipeline.
What AmerisourceBergen's Report Reveals About Payers, Biosimilar Pricing Trends
May 28th 2023On this episode of Not So Different, Tasmina Hydery and Brian Biehn from AmerisourceBergen discussed results from a recent survey, that were also presented at Asembia 2023, diving into the payer perspective on biosimilars and current pricing trends across the US biosimilar industry.
Study: More Biosimilar Competition Is Not Lowering Patient OOP Costs
March 29th 2024Despite more biosimilars entering the market and generating significant savings for payers and health care systems, these savings are not resulting in lower out-of-pocket (OOP) costs for patients, according to a recent study.
Pipelines and Preparation: How the US Can Prepare for More RA Biosimilars
April 16th 2023What can practices do to prepare for all the biosimilars to treat rheumatoid arthritis (RA) coming down the pipeline? And how can they ensure that the lower-than-anticipated adoption rates for infliximab biosimilars are not repeated? Robert Zutaut, RPh, from McKesson Provider Solutions, tackles all this and more on this episode of Not So Different.
The Role of Biosimilars: Advancing Access, Financial Health, and System Sustainability
March 11th 2024Kashyap Patel, MD, CEO of Carolina Blood and Cancer Care, a member of the Community Oncology Alliance, and member of The Center for Biosimilars® Advisory Board, glances back at the development of the biosimilar industry and the last 5 years of progress.