Approval of Alexion Pharmaceutical Inc.'s Soliris (eculizumab) injection to treat neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive makes it the first and only FDA-approved treatment. It's also one of the most expensive treatments in the world, making it vulnerable to off-label use and the eventual creep of biosimilars into the market.

Soliris is Alexion's biggest moneymaker, bringing in net product sales of $962 million in the first quarter of 2019, compared to $800.1 million in the first quarter of 2018, a 20% increase. Soliris' volume has increased 23% year-over-year.

NMOSD, also known as Devic's disease, is Soliris' fourth indication, along with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and generalized myasthenia gravis. (See BioWorld, June 28, 2019.)

Soliris is available only through a restricted program under a risk evaluation and mitigation strategy. Boston-based Alexion estimates 4,000 to 5,000 U.S. NMOSD patients would be eligible for Soliris. NMOSD affects women more than men, at a nearly 10-1 ratio. It also has a high incidence in African American and Asian patients.

Roche Holding AG's Rituxan (rituximab) is an off-label competitor that comes at a significantly lower price to patients (about $60,000 compared to Soliris' $500,000-plus price tag), prompting some to believe Alexion may not get the market penetration it expects. Also, Amgen Inc. is developing a biosimilar, ABP-959, for treating PNH. It is currently in phase III testing and data are expected sometime later this year.

"In the NMOSD pivotal trial, Soliris was given to patients who had prior immunosuppressive therapies and had multiple relapses (>2) over the past 1-2 years. The approved indication has no restrictions by prior treatment (just as the MG label similarly contained no restrictions or limitations by prior therapy). Despite the label, we don't think Soliris will capture significant use in front-line treatment given Rituxan's favorable cost-benefit profile," SVB Leerink analysts wrote Friday. "We expect most insurance payers to require evidence of Rituxan failure before reimbursing for Soliris in this disease, but do expect relatively open access to Soliris for relapsed patients in late line treatment."

Jefferies analyst Eun Yang, in a May report, cited a neurologist as saying about half of AQP4-positive NMOSD patients are currently on Rituxan, given intravenously twice a year, with about 75% achieving remission (i.e., no relapses in three years) and about 12% failing – despite near complete B-cell depletion – because of logistical issues (missing their infusion days or finding that their payers denied coverage).

Alexion plans to eventually shift nearly three-quarters of patients receiving Soliris to a newer, most likely cheaper drug, Ultomiris (ravulizumab), in the next two years, before biosimilars enter the market.

A phase III study designed to support use of ravulizumab, a long-acting C5 complement inhibitor, in complement inhibitor-naïve patients with aHUS met its primary endpoint, putting the company on track to seek FDA approval for the indication by midyear, with EU and Japanese filings to follow. Though met with skepticism in some quarters over a perceived lack of differentiation from Soliris, Piper Jaffray analyst Christopher Raymond said the results showed Ultomiris holding its own in patients sicker than those in an earlier Soliris trial. (See BioWorld, Jan. 29, 2019.)

Eddie Patton, a neurologist at Mischer Neuroscience Associates – Memorial City and clinical assistant professor in the Department of Neurology and Neurosurgery at University of Texas, said Soliris is better targeted for NMOSD than off-label use, which, up until now, has been the traditional treatment.

"NMOSD is a complementary disease and eculizumab targets the complementary system. All the other treatments have side effects," he told BioWorld. "The great thing is, it gives a targeted and specific treatment for a disease that's historically difficult to treat."

Although the majority, about 70%, of NMOSD patients are well-managed on Rituxan, there remains one-third of patients who suffer disease relapses and are at risk for severe disabilities and death if left untreated, Leerink noted Friday.

Patton described eculizumab treatment for NMOSD as weekly treatments, then tapering off to every two weeks, "so it's not that long a period. It tends to work pretty fast. You see the results pretty quickly."

Shares of Alexion (NASDAQ:ALXN) closed up 3.86% on Friday, at $130.98 per share.

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