Washington Editor

Alexion Pharmaceuticals Inc. filed for FDA approval of Soliris (eculizumab) to treat a life-threatening blood disorder called paroxysmal nocturnal hemoglobinuria (PNH).

"For PNH, there is no safe and effective therapy that's been approved anywhere in the world," Alexion CEO Leonard Bell told BioWorld Today.

The rare genetic condition is characterized by the destruction of red blood cells by the body's complement system, a component of the immune system. Patients lack naturally occurring complement inhibitors that normally prevent red blood cell destruction. "They're missing that shield," Bell said, and noted the deleterious effects of that: low blood counts and free-floating hemoglobin. But the monoclonal antibody Soliris is designed to selectively block terminal complement activation and thereby restore complement inhibition in PNH patients' blood.

The Cheshire, Conn.-based company requested priority review from the FDA, setting up the possibility of a regulatory decision by the middle of next year. In addition, Alexion remains on track to file for Soliris' European approval by the end of this year, where the product already has been granted accelerated review status.

Dosed every two weeks by way of a 20- to 30-minute infusion, Soliris has been used in some patients for more than four years. Its biologics license application is based on Phase III data from a pivotal study called TRIUMPH, which met all pre-specified primary and secondary endpoints. Preliminary findings showed that the median transfusion rate dropped from 10 units per patient with placebo to 0 units per patient with Soliris (p<0.000000001), and hemoglobin stabilization was achieved by 49 percent of Soliris patients as compared to none for placebo (p<0.0000001). (See BioWorld Today, Jan. 27, 2006.)

In contrast, current treatments include vitamins and transfusions to boost blood supply as well as blood thinners to combat clotting, but nothing that combats the underlying cause of the disease.

The TRIUMPH trial, which was published in Thursday's edition of The New England Journal of Medicine, included 87 PNH patients.

The disease, which typically first surfaces in early adulthood as a result of DNA mutations, increases the risk of blood clots, and patients die within 10 years to 15 years of diagnosis. Along the way, PNH causes hemolysis, anemia, chronic fatigue, recurrent pain, pulmonary hypertension and hemoglobinuria, which is characterized by intermittent episodes of dark-colored urine.

The submission also includes interim data of at least six months from an open-label Phase III safety trial called SHEPHERD, and final 12-month data will be added to the application down the road. To date, it has enrolled 97 patients. An additional 11 PNH patients were enrolled in an earlier pilot study.

The FDA and European regulators have named Soliris an orphan drug in this indication, which is estimated to affect between 8,000 and 10,000 people in North America and Europe. Alexion, which has begun laying its marketing groundwork, plans to commercialize the product on its own in both territories, where hiring already is under way in preparation for a launch next year.

"We feel like a company like ours can give the best attention and deliver the best value to patients worldwide," Bell said. "We can focus on them, we can give them the service and a product that can help them transform their lives."

Analysts have speculated that its pricing could total six figures per patient, though Bell declined to discuss its projected cost. While he conceded that it could be "valued at a premium" like other drugs that provide a transformative therapy for treating rare diseases, he said studies and analyses are being used to determine its appropriate costs in different countries.

Next year, the company plans to begin testing its use in organ transplant patients.

Soliris' ascent stands apart from the fall of pexelizumab, a monoclonal antibody fragment designed to inhibit complement-mediated tissue damage in myocardial infarction. Late last year, it failed to hit statistical significance, although it reduced the primary endpoint - nonfatal heart attack or death through 30 days after coronary artery bypass graft surgery, in moderate to high-risk patients. (See BioWorld Today, Nov. 28, 2005.)

On Thursday, shares in Alexion (NASDAQ:ALXN) traded down 63 cents to $32.79.