Investors gained evidence that DX-88 development is fully back on track, as Dyax Corp. reported positive data from the first of two Phase III trials of the product in treating hereditary angioedema.

The 72-patient EDEMA3 trial hit the primary endpoint and both secondary endpoints, uplifting investors who last year saw development of DX-88 set back a year or so when the FDA said a confirmatory trial, EDEMA4, would be needed. Dyax's stock (NASDAQ:DYAX) gained $1.97 Friday, or 49.3 percent, to close at $5.97; it traded as high as $6.95.

"Everybody is very excited," said Ivana Magovcevic-Liebisch, general counsel and executive vice president, corporate communications at Cambridge, Mass.-based Dyax. "People feel that the risk is taken out of this program since EDEMA4 is a duplicate of EDEMA3."

Eugene Trogan, a vice president of equity research at Morgan Joseph & Co. Inc. in New York, said, "The news was tremendously positive for Dyax." He noted that not only did it meet the endpoints, but also appeared to do so in an impressive manner.

The placebo-controlled EDEMA3 trial demonstrated a statistically significant improvement (p=0.021) in symptom improvement at four hours as measured by a treatment outcome score, the primary endpoint. The trial also proved (p=0.024) an improvement in symptom burden at four hours as measured by the Mean Symptom Complex Severity score, or MSCS. And it showed a quicker time to significant improvement in overall response, with a median time of 149 minutes vs. more than 240 minutes for the placebo group (p=0.044).

Dyax will present more detailed information from the study in a webcast Tuesday.

While the EDEMA4 trial will be very similar, there are a few slight differences. Magovcevic-Liebisch said the trial is designed to enroll 52 patients instead of the 72 in EDEMA3, and that the primary endpoint will be switched with one of the secondary endpoints. EDEMA4 primarily will evaluate MSCS scores, a patient-reported assessment of symptoms. Secondary endpoints will be symptom improvement at four hours measured by treatment outcome scores, and time to significant improvement in overall response.

Hereditary angioedema, or HAE, is an acute inflammatory condition characterized by episodes of severe, often-painful swelling affecting the extremities, the gastrointestinal tract and, in life-threatening cases, the larynx. HAE is caused by low or dysfunctional levels of C1 esterase inhibitor, Dyax said.

Magovcevic-Liebisch told BioWorld Today that estimates have shown there are about 10,000 immediately addressable HAE patients in the U.S. and Europe, and "we believe there are probably 30,000 patients in the U.S. and Europe. It's a pretty large number for an orphan indication."

While the EDEMA4 trial in a sense is under way, with patient enrollment having begun, none of those patients has suffered an HAE attack, so there has been no treatment. Dyax will wait until the first patient is treated to formally announce the start of the trial, Magovcevic-Liebisch said.

Dyax is not providing guidance on the expected timelines on the trial, but is saying that approval is expected in late 2008 if all goes as planned.

By that time, the competitive landscape for HAE treatments should be much clearer, as at least four other products are in late-stage development. DX-88 (ecallantide) is different from the potential competitive agents in that it is a recombinant, plasma kallikrein inhibitor delivered by subcutaneous injection. Three of the other products are C1 inhibitors, delivered intravenously, and the fourth is a bradykinin receptor antagonist, a target downstream from kallikrein, Magovcevic-Liebisch said.

"The only real competitor for Dyax," Trogan told BioWorld Today, is Icatibant, a subcutaneously administered synthetic peptidomimetic agent being developed by Jerini AG, of Berlin, in partnership with Cranbury, N.J.-based Kos Pharmaceuticals Inc. (now part of Abbott Laboratories). One Phase III trial of Icatibant, FAST-2, demonstrated statistical significance, while the other, FAST-1, did not.

Jerini plans to use combined data from the two studies, which together demonstrated statistical significance, in a new drug application filing with the FDA that is expected in the third quarter, Trogan said.

He said it is unclear whether the FDA would approve the Jerini drug on that basis, though he believes it ultimately will be approved. "I think it works," he said.

He believes the Dyax drug also works, and said a number of physicians have told Morgan Joseph that DX-88 and Icatibant appear to have similar efficacy and safety.

Those injectable drugs would have a big advantage over intravenous drugs because of the ease of administration, that it would not have to be done in a hospital setting, Trogan said.

That's because HAE attacks can come on suddenly, and patients don't know what type of attack they will get. "Having a product patients can use themselves by subcutaneous injection is a tremendous benefit," he said.

He added, however, "I still think there is a use for IV administration in a hospital setting" for HAE patients.

The front-runner in that area is New York-based Lev Pharmaceuticals Inc., which last month reported its C1 inhibitor met the primary endpoint in a pivotal Phase III study. Lev said then that, pending a meeting with the FDA, it expects to submit a biologics license application this quarter.

ZLB Behring, of King of Prussia, Pa., is in Phase III studies with its C1 inhibitor, Berinert P, while Pharming Group NV, of Leiden, the Netherlands, said it expects to complete Phase III studies this year of Rhucin, its C1 inhibitor derived from the milk of transgenic rabbits.

Dyax had been in a long-term relationship with Genzyme Corp., also of Cambridge, on DX-88 development for HAE. They began working together in 1998, and in 2003 Genzyme exercised its option to establish a joint venture. The venture formally ended in February, with Genzyme citing other priorities in opting out of the relationship. Genzyme paid $17 million to Dyax to cover its funding commitments for the program, and Dyax issued 4.4 million shares to Genzyme to acquire its 50 percent stake in the venture.

Dyax now has full rights to DX-88, which also is Phase II development for preventing blood loss during on-pump coronary artery bypass graft surgery. While Dyax already owned full rights to that second indication, the termination of the deal with Genzyme did take away potential questions that could pop up later, since it is the same molecule and same formulation.

As for partnering plans, Magovcevic-Liebisch said, "We are looking at all our options. We now have complete control of the molecule. We will do what makes the most sense, what brings the biggest value to Dyax and its shareholders."