Eculizumab Approved in Europe for NMOSD, Another Candidate Moves Forward in the United States

This week saw a pair of developments for patients with neuromyelitis optica spectrum disorder (NMOSD), a rare, severe, relapsing, neuroinflammatory autoimmune disease that can be fatal.

First, the European Commission approved brand-name eculizumab (Soliris) for the treatment of adults with NMOSD who are anti-aquaporin-4 (AQP4) antibody positive. The drug maker, Alexion Pharmaceuticals, received FDA approval for the same indication in June.

NMOSD mainly affects the optic nerves and spinal cord. NMOSD can be associated with antibodies that bind to the AQP4 protein; this binding appears to activate other components of the immune system, causing inflammation and damage to the central nervous system.

Soliris faces upcoming biosimilar competition from products including SB12, Samsung Bioepis’ biosimilar candidate, which is enrolling a phase 3 clinical study in patients with paroxysmal nocturnal hemoglobinuria. Also advancing is Amgen’s ABP 959, which recently was reported to have pharmacokinetic and pharmacodynamic equivalence to reference eculizumab. Earlier this year, Alexion said it hopes to transition patients already receiving its eculizumab onto a newer drug, ravulizumab (Ultomiris), in the future.

Separately, Viela Bio announced that the FDA has accepted for review its Biologics License Application (BLA) for inebilizumab, an investigational anti-CD19 monoclonal antibody, for NMOSD.

“The acceptance of our first BLA filing for review represents a huge milestone for inebilizumab and another important step in delivering this novel therapy to patients in need,” Jorn Drappa, MD, PhD, chief medical officer and research and development head, said in a statement. “We believe that inebilizumab can play a critical role in reducing the risk of developing an NMOSD attack, thereby contributing to the health of patients with this devastating and debilitating disease. We look forward to working closely with the FDA to move this therapy toward approval.”

The safety and efficacy results are from the pivotal N-MOmentum trial, the largest global, placebo-controlled study in NMOSD. The study, which enrolled 231 patients with and without the AQP4-IgG antibody, met its primary and a majority of the secondary endpoints.

Results demonstrated that inebilizumab reduced the risk of developing an NMOSD attack by 77% when compared to placebo in AQP4-IgG seropositive patients after 28 weeks of treatment. In addition, inebilizumab impacted measurements of worsening disability, hospitalizations and new central nervous system MRI lesions.

Inebilizumab is given every 6 months, whereas eculizumab is given every 2 weeks. In its pivotal trial, eculizumab reduced the number of NMOSD relapses by 94%.

Inebilizumab received Orphan Drug Designation from both the FDA and the European Medicines Agency in March 2016 and March 2017, respectively.

The drugs work differently, noted a recent report, and direct comparisons are tricky; the report noted that there is another candidate, satralizumab, which is given subcutaneously once a month. Results from that trial range from a reduction in attack risk of 62% across antibody-positive and negative patients to a 79% reduction when looking at solely at patients positive to AQP4.

NMOSD is believed to affect 4000 to 8000 patients in the United States. According to the National Institutes of Health, women are more often affected by NMOSD than men; African Americans are at greater risk of the disease than Caucasians.