Top-line results from the phase III PREVENT study testing Soliris (eculizumab) in rare disease neuromyelitis optica spectrum disorder (NMOSD) "far exceeded our expectations," said Ludwig Hantson, CEO of Alexion Pharmaceuticals Inc., which is now moving to engage regulators on submissions to expand use of the complement inhibitor in NMOSD, a complement-mediated disorder for which there currently are no approved therapies.

Estimated to affect roughly 8,000 patients in the U.S., NMOSD is a relapsing autoimmune disorder that attacks the optic nerve and spinal cord. Each relapse adds to a patient's disability, such as optic neuritis leading to eye pain and blindness and transverse myelitis leading to severe weakness and increasing sensory and motor disability, possible paralysis and death. Roughly one-third of patients suffer permanent motor disability and nearly one in 10 die from the disorder.

NMOSD, which primarily affects women, is caused by production by the immune system of auto-antibodies against AQP4, a protein found on certain cells in the brain and spinal cord that are critical for the survival of nerve cells. Binding of those anti-AQP4 auto-antibodies activates the complement cascade. Alexion's study, PREVENT, was designed to enroll specifically NMOSD patients with anti-AQP4 auto-antibodies, a subgroup that represents about three-fourths of the overall patient population.

PREVENT enrolled 143 adults with confirmed diagnoses of NMOSD, who were also seropositive for anti-AQP4 auto-antibodies and had a history of at least two relapses in the last 12 months or three relapses in the last 24 months. Patients were randomized 2-to-1 to receive Soliris or placebo. They were allowed to receive stable maintenance doses of permitted immune suppressive therapies for relapse prevention.

On the primary endpoint, defined as the time to first on-trial relapse – adjudicated by an independent committee comprising three external experts blinded to treatment – Soliris reduced the risk of NMOSD relapse by 94.2 percent vs. placebo (p<0.0001). At 48 weeks, 97.9 percent of patients receiving Soliris were free of relapse compared to 63.2 percent of patients receiving placebo. Treatment with Soliris also reduced the adjudicated on-trial annualized relapse rate compared to placebo, a key secondary endpoint, by 95.5 percent (p<0.0001).

Other secondary endpoints including disability and quality of life measures showed only small differences, though they favored Soliris. Alexion said that was not unusual, given that disease worsening is driven by damage incurred following relapse.

Overall, Soliris was generally well-tolerated with a safety profile consistent with that seen in previous clinical studies and real-world use.

An open-label extension study is ongoing, with 119 patients, who completed PREVENT either because of relapse or because the study ended, enrolled.

With the data in hand, Boston-based Alexion is looking to meet with regulators in the U.S., Europe and Japan as quickly as possible.

"With this dataset likely fileable, we wouldn't be surprised to see this indication approved by next year-end," Piper Jaffray analyst Christopher Raymond wrote in a research note, calling the PREVENT read-out "overwhelmingly positive."

Given that data weren't anticipated until the end of this year and "management's cautious commentary heading into the 'high risk' event, we think few were expecting to see data as compelling as today's read-out," Raymond added.

Soliris, which is approved for rare and ultra-rare disorders including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome and myasthenia gravis, has been Alexion's top-seller since first gaining FDA approval for PNH in 2007. In 2017, the company posted net product sales for Soliris totaling $3.14 billion.

Adding NMOSD could boost that even higher. In light of the top-line PREVENT data, Evercore ISI analyst Josh Schimmer updated estimates for peak worldwide sales of Soliris in the new indication to about $930 million.

Shares of Alexion (NASDAQ:ALXN) gained $6.52 to close Monday at $128.51.