West Coast Editor

In the pull-ahead, fall-back race for a drug against hereditary angioedema (HAE), Dyax Corp. regained some lost ground with news that Icatibant - the synthetic peptidomimetic from would-be competitors Kos Pharmaceuticals Inc. and Jerini AG - missed its primary endpoints in one Phase III trial, but hit the primary endpoint in another.

Cambridge, Mass.-based Dyax's stock (NASDAQ:DYAX) closed at $3.40, up 53 cents, or 18.5 percent.

Jens Schneider-Mergener, CEO of Berlin-based Jerini, congratulated his firm's research and development people for "wonderful" work, and told investors during a conference call that Icatibant "achieved very significant results showing a clear effect." But Wall Street's reaction on the Dyax side told another story.

"The feeling at the moment is that they may have to verify that primary endpoint by doing another study," said Richard Smith, analyst with JPMorgan in New York.

Icatibant reached its primary endpoint - median onset of symptom relief as compared to tranexamic acid in the 74-patient trial called FAST-2, held in Europe and Israel, but missed the same endpoint in FAST-1, which enrolled 56 patients in the U.S., Canada, Australia and Argentina.

In FAST-2, the drug gained relief at two hours, compared to 12 hours with tranexamic acid. In FAST-1, the drug worked in 2.5 hours, compared to 4.6 hours, not enough of a margin to make statistical significance.

European regulators need only FAST-2 to grant approval, and FAST-1 results are only supportive there. The FDA, though, requires two pivotal independent trials, so the data will be pooled.

"The FDA tends not to like that kind of analysis," Smith noted.

Schneider-Mergener, though, called the results "positive and consistent" between the pair of studies (conducted under a special protocol assessment), and vowed to present them to the FDA "in the near future," probably around the end of the year."

Jerini officials blamed the high success rate of placebo for the mixed outcome - a familiar refrain in failed trials.

"We only took one key symptom [abdominal pain] for determination of the primary endpoint," Schneider-Mergener said. Berndt Modig, chief financial officer, remarked that it's "well known that especially pain symptoms are prone to placebo response. We expected that, but we hadn't expected such a magnitude of placebo response."

The method of measurement is subjective, but often used, mainly in pain trials.

"You draw a horizontal line," Smith explained. "At one end is no pain, and at the other end is a lot of pain. They monitor it by asking the patient to draw a line between those two points, and every half an hour, they ask them to do it again."

The main problem with the method could be that it measured only pain, not laryngeal attacks (which are life threatening, and thus difficult to include) or swelling - or a range of symptoms, as Dyax did with questionnaires in trials.

"I feel a lot more confident with that approach," Smith told BioWorld Today.

Earlier this month, Dyax and partner Genzyme Corp., of Cambridge, Mass., heard from the FDA that the company needs to complete a confirmatory Phase III trial with its HAE candidate, the kallikrein inhibitor DX-88, pushing out launch until the second half of 2008. (See BioWorld Today, Sept. 5, 2006.)

The delay seemed to signal that Kos/Jerini's drug would land on the market ahead of Dyax/Genzyme's compound, but the latest developments could mean DX-88 will be approved first.

"I think it's possible," Smith said.