West Coast Editor
Almost two months after taking a hit on bad news from a late-stage trial with its heart drug, Alexion Pharmaceuticals Inc. reported much more pleasing preliminary results from a pivotal Phase III study testing the monoclonal antibody Soliris (eculizumab) against transfusion paroxysmal nocturnal hemoglobinuria (PNH), a rare form of hemolytic anemia.
Soliris, a long-acting C5 terminal complement inhibitor, "knocked the cover off the ball, on the way to knocking the ball out of the park," said Leonard Bell, CEO of Cheshire, Conn.-based Alexion, during a conference call.
"I would think there is a strong likelihood we would reallocate resources from our [acute myocardial infarction] program to PNH" as a result of the strong data, Bell later told BioWorld Today.
Wall Street cheered. Alexion's stock (NASDAQ:ALXN) closed Thursday at $26.40, up $4.45, or 20.3 percent.
In the PNH study known as TRIUMPH, pre-specified, co-primary endpoints were median transfusion rate and hemoglobin stabilization over six months. The median transfusion rate dropped from 10 units/patient with placebo to 0 units/patient with eculizumab (p<0.000000001), and hemoglobin stabilization was achieved by 49 percent of eculizumab patients as compared to none for placebo (p<0.0000001).
TRIUMPH enrolled 87 patients at 45 sites in the U.S., Canada, Europe and Australia. Also achieving statistical significance were all of the secondary endpoints, which included avoidance of transfusion, reduction in lactate dehydrogenase and quality of life as measured by the Functional Assessment of Chronic Illness Therapy Fatigue.
The drug appeared to be well tolerated with an adverse event profile comparable to placebo. The most frequent adverse events with eculizumab were headache, nasopharyngitis (cold symptoms) and back pain.
Bell said the full data, which he called "outstanding," will be published in a scientific journal to be decided.
Another study with Soliris - newly branded by the company - against PNH, called SHEPHERD, is ongoing. Primarily aimed at generating safety data in a broader population, the trial also will get efficacy measures. Patients will undergo 12 months of treatment with a six-month interim analysis, and data from TRIUMPH and SHEPHERD together will be included in the biologics license application, as well as the European Marketing Authorization Application.
Those regulatory filings are expected during the second half of this year, and Soliris has been granted orphan drug status in the U.S. and Europe. Both trials are the subjects of an FDA special protocol assessment.
About 8,000 to 10,000 people in North America and Western Europe are estimated to suffer from PNH, which can bring severe hemolysis, anemia, chronic fatigue, recurrent pain, pulmonary hypertension and episodes of dark urine, known as hemoglobinuria. They also are at increased risk of forming life-threatening blood clots, a leading cause of death in PNH.
"This is a disease where half the patients die within 10 to 15 years of diagnosis," Bell pointed out, putting its market potential in the range of such drugs as Fabrazyme, Cerezyme and NovoSeven.
NovoSeven, from Bagsvaerd, Denmark-based Novo Nordisk A/S, is a recombinant coagulation Factor VIIa approved for bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX. Genzyme Corp., of Cambridge, Mass., markets Cerezyme (imiglucerase for injection) for Type I Gaucher's disease and Fabrazyme (agalsidase beta), the enzyme-replacement therapy for Fabry's disease. Earlier this month, Genzyme reported that Cerezyme sold $232 million in the fourth quarter, and Fabrazyme $81 million.
Bell said he expects Soliris to be priced "comparably" to those products, given the serious nature of PNH and the fact that no treatment exists specifically for the condition. During the conference call, Bell said that exact pricing has not yet been determined, "nor would it be appropriate to comment," though orphan drugs "often command annual prices in the range of $100,000 to $200,000 or more."
In November, Alexion's stock fell more than 27 percent on word that its monoclonal antibody fragment pexelizumab, aimed at inhibiting complement-mediated tissue damage, 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.)
Alexion is still assessing the impact of the pexelizumab study, known as PRIMO-CABG2, in its ongoing Phase III trial with the same drug against acute myocardial infarction, with partner Procter & Gamble Pharmaceuticals Inc., a unit of Cincinnati-based Procter & Gamble Co.