Alexion to Seek Fourth Indication for Eculizumab Ahead of Biosimilar Competition

Drug maker Alexion says that it is preparing for regulatory submissions in the United States, the European Union, and Japan for eculizumab (Soliris) for the treatment of anti-aquaporin-4 auto antibody-positive neuromyelitis optica spectrum disorder (NMOSD).

NMOSD is a rare, complement-mediated demyelinating disorder of the central nervous system that primarily affects the optic nerves and spinal cord, leading to blindness and paralysis. The disorder was once thought to be related to multiple sclerosis, but with the identification of a unique biomarker antibody, NMOSD was understood to be a distinct disease state.¹

While typical treatment for NMOSD includes the use of corticosteroids, plasma exchange, and immunosuppressive medications (including anti-CD20 monoclonal antibodies such as rituximab), there is currently no approved treatment for NMOSD, and Alexion hopes that its eculizumab could become the first authorized therapy.

Read more about eculizumab.

Alexion studied eculizumab in patients with antibody-positive NMOSD in the phase 3 PREVENT trial, a multinational, double-blind, parallel-group, time-to-event study in 143 patients. The patients were randomized 2 to 1 to receive either eculizumab or placebo, and the primary endpoint was the time to the first on-trial relapse.

The study met its primary endpoint, having demonstrated that treatment with the study drug reduced the risk of relapse by 94.2% versus placebo (P <.0001). At 48 weeks of treatment, 97.9% of patients receiving eculizumab were free of relapse versus 63.2% of patients receiving the placebo.

Eculizumab was generally well tolerated, and its safety profile was consistent with that seen in previous clinical studies and real-world use in other indications. No cases of meningococcal infection—an adverse event of particular concern with eculizumab&mdash;were observed.

“These results far exceeded our expectations,” said John Orloff, MD, executive vice president and head of research and development at Alexion, in a statement. “The remarkable reduction in relapse risk demonstrates the unique ability of Soliris to inhibit complement, and suggests a promising new treatment for NMOSD.” Orloff added that the company is “moving quickly” to file for approval of the new indication.

Eculizumab is already approved to treat 3 other rare diseases: paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, and generalized myasthenia gravis. Given the high cost of the drug, adding a fourth indication for the drug could bring in an additional $500 million to $700 million to Alexion, say some analysts. At a list price of approximately $500,000 per patient per year, eculizumab is one of the most expensive therapies in the world.

Yet Alexion’s profitability in this area could be challenged in the near future; the molecule is targeted by at least 1 biosimilar developer; Amgen is currently engaged in a phase 3 study in Spain that evaluates the efficacy and safety of its proposed biosimilar, ABP 959, versus the reference eculizumab in patients with PNH. However, Alexion is hoping to stave off biosimilar competition with a set of 3 patents, awarded in August 2017, that will extend protection for the brand-name Soliris until 2027.

Reference

1. Kessler RA, Mealy MA, Levy M. Treatment of neuromyelitis optica spectrum disorder: acute, preventative, and symptomatic. Curr Treat Options Neurol. 2016;18(1): 2. doi: 10.1007/s11940-015-0387-9.