Eculizumab Shows Better Prolonging of Time to NMOSD Relapse Than Other Treatments

Sean Pittock, MD

Using a Bayesian network meta-analysis (NMA), findings showed that treatment with eculizumab (Soliris; Alexion) monotherapy and combination of eculizumab and immunosuppressant (IST) has greater success in prolonging time-to-first relapse in patients with aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) compared with other FDA-approved treatments.1

Senior author Sean J. Pittock, MD, director, Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, presented these data at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), October 13-15. Pittock and colleagues extracted data from randomized controlled trials that reported the relative treatment effects of these therapies. Additionally, the analysis sorted subpopulations based on 3 treatment networks: monotherapy, combination therapy, and mixed mono-combination therapy.

A regression model comprised of a contrast-based normal likelihood for the log HR and the corresponding standard error of each trial in the network was used to calculate time-to-first relapse. Time-to-first relapse was the only outcome measure reported across the RCTs.

At the conclusion of the analysis, time-to-first relapse was 90% less likely for patients on eculizumab monotherapy than for those on satralizumab (Enspryng; Genentech) monotherapy (HR, 0.10 [95% credible interval (Crl), 0.01-0.65]). Furthermore, these patients were also 89% less likely to experience a first relapse compared to patients on inebiluzumab (Uplizna; Horizon) monotherapy (HR, 0.11 [95% Crl, 0.02-0.68]). A combination approach using eculizumab and IST was also found to be associated with a 76% less likelihood to experience a first relapse compared to satralizumab with IST (HR, 0.24 [95% Crl, 0.06-0.98]).

The discovery of AQP4 led to the breakthrough of the first treatments for NMOSD in 2019 with eculizumab. Following that, the FDA then greenlit inebilizumab in June 2020 and satralizumab in August 2020. Corticosteroids and immunomodulatory or ISTs have also shown benefit within this patient population. Pittock has had first-hand experience with understanding the clinical pipeline of the disease, serving as an investigator for multiple trials such as PREVENT (NCT01892345) of eculizumab and N-MOmentum (NCT02200770) of inebilizumab.

Most recently, he and his colleagues published post-hoc findings from PREVENT and its open-label extension (NCT02003144), which highlighted eculizumab’s safe and effective profile as a long-term, monotherapy option. Findings showed the treatment provided relapse protection seen previously in clinical trials and helped patients avoid the use of off-label IST.2

In September 2021, Pittock sat down with NeurologyLiveto discuss the state of the disease space, noting that, “Now that we have 3 drugs, there are issues that are related to those specific drugs, one being cost. These are very costly medications. Though they may be available to patients in the US covered by insurance, there are many patients around the world who don’t have access or potentially won’t have access to these medications.”