West Coast Editor

As the race continues for marketing clearance of a therapy for hereditary angioedema, the specialty pharma firm Kos Life Sciences has put its chips on Jerini AG, of Berlin, paying the company 22 million (about US$27 million) for rights to develop, market and distribute the Phase III compound Icatibant.

"I'm not sure it's quite a race, since they won't exclude each other from the marketplace," noted Gregory Wade, analyst with Pacific Growth Equities in San Francisco. Wade covers Dyax Corp., which also has a Phase III-ready HAE drug.

Shares of Kos Pharmaceuticals Inc. (NASDAQ:KOSP), of which Kos Life Sciences is a subsidiary, closed Monday at $57.86, down $1.48. Dyax's stock (NASDAQ:DYAX) closed Monday at $4.65, up 4 cents.

Under the terms, Kos is paying 12 million up front as a licensing fee, and making an equity investment of 10 million, paying the weighted average of the closing price of Jerini's shares during the last four trading days, or 3.20 per share - which is the price at which Jerini shares settled on the day of the firm's initial public offering. The stock opened on IPO day at 3.10, under the low end of the sought range of 3.20 to 3.60, raising 51.5 million.

Shares of Jerini (FSE:JI4) closed Monday at 3.14, up .02.

Undisclosed milestone payments and sales royalties are included in the deal, which outlines collaborative efforts not only in HAE but also in other forms of angioedema with larger patient groups, plus asthma and refractory ascites in liver cirrhosis (RAIL), which affects about 300,000 globally per year. Proof-of-concept trials already have been completed in those indications.

Kos will be responsible for Icatibant's clinical development in asthma (as an inhaled product) and refractory ascites in liver cirrhosis (by intravenous injection). Jerini retains commercial rights to Icatibant outside the U.S. and Canada while continuing to be responsible for HAE Phase III trials (ongoing in the U.S., Canada and Europe) as well as regulatory approval.

Trial results are expected in mid-2006, with filing for market approval in the U.S. and Europe also planned in 2006. Phase II results show a 100 percent response rate, Kos said, and the ongoing Phase III trials are supported by a special protocol assessment from the FDA, and include the treatment of life-threatening laryngeal attacks as part of an open-label extension study.

Jerini plans studies with the drug for idiopathic and drug-induced angioedema with Icatibant next year. In HAE and other forms of angioedema, Kos and Jerini will collaborate on the global branding and positioning. Jerini will continue to be responsible for the supply of the drug, a bradykinin B2 receptor antagonist.

About a year ago, Dyax Corp., of Cambridge, Mass., with its same-city partner Genzyme Corp. - which Dyax's CEO Henry Blair co-founded in 1981 - said the company expected to beat Jerini to market with DX-88, the inhibitor of kallikrein (which is bradykinin's enzymatic "liberator" in the body) for HAE, after completing more clinical work requested by the FDA. (See BioWorld Today, Oct. 25, 2004.)

Both compounds have orphan drug status and fast-track designation from the FDA. Dyax said a Phase III trial with DX-88 is expected to start by the end of this year, with a filing of the biologics license application in 2006, and the European filing soon after, according to the company's most recent quarterly report. U.S. approval is expected in 2007.

"We haven't seen enough data from the Jerini product to make the full characterization [regarding which is better]," Wade told BioWorld Today. "But the data we've seen from Dyax is extremely promising."

Dyax's Blair pointed out that his firm's results with DX-88 are "extraordinarily public, whereas the Jerini program is absolutely not public. If Kos really wants to come across and tell us exactly where that program stands, fine. But they have told no one where it stands, not even in their public offering."

The press release from Jerini on the deal boasts that Icatibant has been proven safe in more than 1,000 patients.

"That's a real crock," Blair said, adding that Icatibant is "an old drug. How many of those patients are HAE?" DX-88, he said, has been administered 297 times to 107 patients. One experienced flushing but "still responded positively to the drug." In the particularly acute setting of an HAE attack, the Dyax drug has treated 33 events in 20 patients, "100 percent of them successfully," Blair said.

"I've been taking the high road [with regard to Jerini], but these half-truths are annoying," he said.

A rare genetic disease that can be painful, debilitating and life-threatening, HAE is characterized by recurrent local swelling of subcutaneous tissue, the gastrointestinal tract and the larynx, the last of which can lead to suffocation. About 10,000 HAE patients have been diagnosed in the European Union and the U.S.; experts believe the condition could afflict as many as 75,000 throughout the world, Kos said. Wade said estimates vary widely, but his firm put the number at about 26,000 patients in the U.S.

John Howarth, Cranbury, N.J.-based Kos' vice president of investor relations and corporate affairs, noted that "getting medical education programs geared up, and letting people know this kind of compound is out there" will be important, adding that Jerini "found [in us] a company with a very aggressive sales force and a focused approach to detailing."

Kos about a week ago reported third-quarter revenue increased 56 percent to a record $205.1 million, up from $131.9 million for the third quarter of 2004, thanks to growth of the cholesterol products Niaspan and Advicor, as well as solid earnings from Cardizem and Teveten, the cardiovascular products gained from Toronto-based Biovail Corp. for $104 million this spring. (See BioWorld Today, May 4, 2005.)

Another drug in Phase III testing for HAE is New York-based Lev Pharmaceuticals Inc.'s, C1-esterase inhibitor, which started in the first quarter. Pharming Group NV, of Leiden, the Netherlands, in May reported positive results from Phase II/III studies with its C1 inhibitor.