Alexion Aims To Drive PNH Diagnoses (And Soliris Sales) With Diagnostic

Alexion believes the challenge of identifying new patients with the "ultra-orphan" blood disorder paroxysmal nocturnal hemoglobinuria who are candidates for the company's biologic Soliris (eculizumab) will be helped by diagnostic technology recently in-licensed by the firm.

During the second quarter, Alexion acquired exclusive worldwide rights to the reagent Fluorescent Aerolysin, or FLAER, from Johns Hopkins University and the University of Victoria in British Columbia.

"The FLAER test has been shown to permit a more accurate determination of the size of the PNH clone as compared to standard flow cytometry," Alexion said. The size of the PNH clone, or the cells affected by the acquired genetic defect causing PNH, dictates the severity of the condition.

Flow cytometry measuring glycoproteins CD55 and CD59 has been the definitive test for PNH; the GPI-anchored proteins are missing on the surface of PNH clones, according to the Alexion-sponsored Web site ¹ www.pnhsource.com. The commercially available FLAER reagent binds to the GPI anchor more specifically and sensitively than the standard process.

"Essentially, the FLAER reagent is substituted for other reagents in the standard flow cytometry test," Alexion CEO Leonard Bell told a June 25 earnings call. "Thus, use of the FLAER test will both improve diagnosis and also employ currently available equipment and methods."

"Greater access to FLAER will likely meaningfully impact the clinical diagnostic rate as well as the accuracy of diagnosis for PNH," Bell predicted, noting that Alexion is in the process of identifying ways to best use FLAER to improve early diagnosis.

Every diagnosis counts for Soliris: PNH affects 8,000 to 10,000 people in the U.S. and Europe. The biologic cleared the agency March 16, 2007. Alexion says its annual pricetag of $389,000 is in line with other "ultra-orphan" products (² (Also see "Alexion’s Soliris Blood Treatment Will Cost Almost $400,000 Per Year" - Pink Sheet, 2 Apr, 2007.), p. 5).

"At the end of the second quarter there were approximately 295 patients on clinical and commercial Soliris worldwide," Bell said. Sales in the U.S. and Europe, where Soliris was approved in June, totaled $9.8 million.

"Most of the use of Soliris in the United States is coming from physicians without previous Soliris experience," Bell said.

Fatigue and quality of life are "the major drivers" in bringing new patients to Soliris, Bell said, followed by anemia and thrombosis. Alexion's push to include fatigue and QOL statements in labeling was a sticking point with FDA.

"What's surprising to me is that early on in the launch it's not heavily transfused patients that are dominating the patient mix of new patients," Bell said. "It's not patients who've had multiple thrombi," but patients with "somewhat less of the disease activity."

In June, Alexion announced a dramatic increase in the size of EXPLORE, a study of PNH frequency in patients with aplastic anemia, myelodysplastic syndromes, and other bone marrow disorders. The new 10,000-patient target is five times the original enrollment goal of 2,000 subjects.

EXPLORE has enrolled over 1,500 AA or MDS patients. "The concomitant PNH frequency continues to track in the 2 to 5 percent range, as anticipated," Bell told Alexion's first-quarter earnings call May 1.

"The EXPLORE study data is particularly useful in educating hematologists and oncologists on the clinical characteristics of PNH in their patients with bone marrow disorders," Bell said to the June call. Alexion is also considering an EXPLORE-style study of PNH in the thrombosis setting.

Alexion anticipates expanding Soliris use to other diseases through "a series of physician-driven and Alexion-sponsored clinical studies," Bell said.

Many neurological diseases "appear to be strongly complement mediated, and most of these are really in the prevalence of PNH." The first target will be multifocal motor neuropathy; a small MMN study will "commence later this year," Bell predicted.

"We're also on track to begin clinical studies with eculizumab in asthma by the fourth quarter," he said.

[Editor's note: This story appears courtesy of the editorial staff of Pharmaceutical Approvals Monthly , your source for coverage of drug development and approvals, including tracking of pending applications. For a sample copy, call customer service at 800-332-2181.]

- Bridget Silverman ([email protected])