Washington Editor

Dyax Corp.'s experimental drug DX-88 (ecallantide) met its goal of reducing symptoms of hereditary angioedema (HAE) in a second Phase III trial, sending shares of the firm up 15.5 percent Monday.

The Cambridge, Mass-based firm's stock (NASDAQ:DYAX) closed at $5, up 67 cents.

Dyax said it plans to submit a biologics license application to the FDA early in the fourth quarter for DX-88 as a therapy for acute HAE, a potentially life-threatening genetic disorder that causes unpredictable inflammatory attacks of the larynx, abdomen, face, extremities and urogenital tract.

There currently are no treatments approved by the FDA for HAE, which affects about 10,000 people in the U.S.

However, the FDA is reviewing at least two applications for C1 inhibitors as HAE therapies.

A third drug, Berlin-based Jerini AG's icatibant, which is marketed in Europe to treat acute attacks of HAE, in April was deemed not approvable in the U.S. by the FDA. (See BioWorld Today, April 25, 2008.)

The FDA is expected to make a decision by Oct. 14 for New York-based Lev Pharmaceuticals Inc.'s Cinryze (C1-esterase inhibitor) as a prophylactic therapy only for HAE. Regulators also are reviewing King of Prussia, Pa.-based CSL Behring's application for its C1 inhibitor Berinert-P to treat acute attacks of HAE.

The FDA was set to make a decision about Berinert-P in early September, said Brian Skorney, of Susquehanna Financial Group.

However, the firm recently was notified by the FDA that the agency was postponing its decision because "more slicing and dicing of the data" was needed, Skorney told BioWorld Today.

CSL has not disclosed a new approval action date set by the FDA, he noted.

The delays seen in the review of Cinryze and Berinert-P may give concern as to the prospects of DX-88's approval on the first try, Skorney said. However, he noted that Dyax's BLA is a rolling submission and the FDA has had data in its hands for several years following the initial BLA submission. Additionally, while Lev's and CSL Behring's BLAs only had one pivotal trial, Dyax's has two.

The recent $443 million acquisition of Lev by Exton, Pa.-based ViroPharma Inc. and the $519 million offering by London-based Shire Ltd. for Jerini reflects those firms' "assessment of a significant market opportunity" for drugs to treat HAE in the U.S., Gustav Christensen, chief business officer for Dyax, told investors and analysts Monday during a conference call. (See BioWorld Today, July 7, 2008, and July 16, 2008.)

What sets DX-88 apart from the other investigational drugs for HAE, said William Lumry, a clinical professor of internal medicine at the University of Texas Southwestern Medical School in Dallas, is that it is administered as a subcutaneous injection, whereas the C1 inhibitors under review must be administered intravenously.

He noted that the earlier a patient is treated, the more likely their inflammatory attacks will be stopped and will be less severe.

"If approval is given for home administration, this drug may be very helpful for patients giving them a way to treat themselves easily at home rather than having to go to a hospital or medical office to receive treatment," said Lumry, who was one of the investigators in both of Dyax's Phase III trials of DX-88.

While DX-88 may be the second or third drug approved to treat HAE over the next year, its subcutaneous route of administration provides a competitive advantage vs. the intravenous drugs, said Susquehanna's Skorney.

He surmised that DX-88 will rapidly become the market leader in the treatment of acute HAE attacks following its approval.

DX-88's mechanism of action is different than that of C1 inhibitors in treating HAE, which is caused by a deficiency of C1 esterase inhibitor, a naturally occurring molecule that inhibits plasma kallikrein, a key mediator of inflammation, and other serine proteases in the blood, Lumry noted.

Scientists' understanding of what causes people to swell with hereditary angioedema and perhaps other types of angioedema is an overproduction of a chemical called bradykinin, which causes the blood vessels to leak fluid, leading to swelling, he explained.

"If you block the production of kallikrein, which is what DX-88 does, then there's none around to convert the chemical into bradykinin," Lumry said. "So you don't have the ability to produce bradykinin if you block kallikrein, because kallikrein is required to make bradykinin."

Topline results reported Monday from Dyax's 96-patient, double-blind, placebo-controlled, multicenter, Phase III trial, known as EDEMA4, showed there was a statistically significant improvement in patient-reported symptoms at four hours measured by the Mean Symptom Complex Severity score, with a p-value of 0.01, said Bill Pullman, the firm's executive vice president and chief development officer.

"Because no objective evaluation exists to characterize these attacks, Dyax developed comprehensive patient-reported outcome measurements, which have been validated with the completion of the clinical development program," he told investors and analysts Monday. "We believe these measurements and the resulting data accurately reflect the progression and notably the response to therapy of a single or multiple symptom HAE attack profile."

Overall, there were 16.7 percent of patients in the DX-88 group who reported adverse events, with 43.8 percent in the placebo group, Pullman said.

The adverse effects of DX-88, he added, were mild to moderate "and transient," with the most common being nausea and headache.

There were no severe or no treatment-related serious adverse events and no discontinuations due to adverse effects in the DX-88-treated group, Pullman said, adding that the drug was "very well tolerated," with no injection site reactions of anaphylaxis or hypersensitivity.

"As a recombinant subcutaneously administered therapy, with no risk for viral contamination, our market research suggests that DX-88's profile matches well with what the HAE patients' desire in a treatment," said Dyax CEO Henry Blair. "These characteristics support DX-88 as a potentially important new HAE therapeutic option," he told investors and analysts.