West Coast Editor
Company phraseology such as "update on regulatory pathway" for a drug candidate seldom means good news, and Dyax Corp. proved the point, telling Wall Street that the FDA likely wants more clinical data on DX-88, the kallikrein inhibitor for hereditary angioedema (HAE).
Dyax's stock (NASDAQ:DYAX) toppled 16.4 percent to end trading at $2.90, down 57 cents, well under the 52-week low of $3.51.
Katherine Xu, analyst at Pacific Growth Equities in San Francisco, was surprised by the news, and called the lowered Dyax stock "a steal" for longer-term investors.
"The value is still there," she said, after talking with management. "I feel very optimistic about this."
Cambridge, Mass.-based Dyax and its partner, Genzyme Corp., also of Cambridge, are evaluating options, but said the previously hoped-for 2007 approval date is likely off the table now.
Dyax said a dose-ranging study of DX-88 might be needed to gain marketing clearance, but the finish date for an ongoing Phase III study called EDEMA3 still is set for this year.
The FDA, as part of a consolidation move, recently transferred the DX-88 program from the Center for Biologics Evaluation and Research (CBER) division to the Center for Drug Evaluation and Research (CDER), which then started talks with Dyax, focused on the rationale for the 30-mg, fixed subcutaneous dosing in the EDEMA3 trial.
"CDER had no concerns on safety or efficacy [of the dose], so that's good," Xu said, noting that the level was derived from a dose-ranging study already completed with an intravenous formulation.
"They converted that dose to the subcutaneous, and it's theoretically equivalent - that's why CBER did not have any problems with it," she told BioWorld Today. "I'm trying to figure out what the agency wants. I've asked the company and they aren't sure, either."
Dyax officials could not be reached.
"Why go up and see what's the maximum tolerated dose [in a new dose-ranging trial]?" Xu asked. "And if you go lower, then you run the risk of not having 100 percent response rate," adding that Dyax's leaders "feel they didn't do as good a job as they could educating the CDER people."
Analyst Jennifer Chao, with Deutsche Bank Securities in New York, wrote in a research note that the "somewhat bizarre twist of events" means investors may have to wait about 100 days for clarity, and worst-case scenario would be another dose-ranging Phase II study, with potential interruption of the ongoing Phase III trial.
"A formal sit-down meeting is not expected until after Dyax has resubmitted data for consideration, upon which FDA is expected to respond following a 75-day review," Chao wrote, keeping her "buy" rating on the stock but dropping the price target from $18 to $8.
Meanwhile, other firms are busy with potential therapies for HAE, a rare genetic disease that causes attacks of localized swelling and inflammation.
In April, Berlin-based Jerini AG randomized the last patient in its Phase III trial with Icatibant, a synthetic peptidomimetic, for HAE. Jerini said it expects to offer top-line data from two Phase III studies in the third quarter. Specialty pharma firm Kos Life Sciences Inc., of Cranbury, N.J., last year paid €22 million (then about US$27 million) for rights to develop, market and distribute the bradykinin B2 receptor antagonist. (See BioWorld Today, Nov. 8, 2005.)
Lev Pharmaceuticals Inc., of New York, started a Phase III trial with its C1-esterase inhibitor for HAE in the first quarter of last year, and the drug (like DX-88, which also has orphan drug status) has been designated fast-track by the FDA.
Also on the radar is Leiden, the Netherlands-based Pharming Group, which a year ago reported positive results from Phase II/III studies with its C1 inhibitor against HAE, and in February entered a $30 million partnership with affiliates of Paul Royalty Fund in return for a share of the lead product's eventual sales. (See BioWorld Today, Feb. 6, 2006.)
Though each of the drugs undergoing trials has orphan status, each works differently, and they could coexist on the market.
About 10,000 HAE patients have been diagnosed in the European Union and the U.S., and experts believe the condition could afflict as many as 75,000 throughout the world, although estimates vary widely.
Dyax, which earlier this year netted $30 million through a discounted stock sale, is planning to move the recombinant small protein DX-88 into a Phase IIb trial shortly for the prevention of blood loss during coronary artery bypass graft surgery - a larger indication - and partnering talks are ongoing. In that indication, DX-88 would go up against marketed Trasylol (aprotinin) from Bayer AG, of Leverkusen, Germany. (See BioWorld Today, March 6, 2006.)
Pexelizumab, the monoclonal antibody fragment from Cheshire, Conn.-based Alexion Pharmaceuticals Inc., fizzled in a Phase III study in the CABG indication late last year, but other firms are testing products to reduce complications associated with bypass procedures, including Avant Immunotherapeutics Inc., of Needham, Mass; Zymogenetics Inc., of Seattle; Millennium Pharmaceuticals Inc., also of Cambridge; and XOMA Ltd., of Berkeley, Calif. (See BioWorld Today, Nov. 28, 2005.)