After taking a look at top-line Phase II data disclosed in March, Genzyme Corp. is exercising an option to get half the interest - and agreeing to pay half the development costs - in a program with Dyax Corp. centered on the anti-inflammatory product DX-88.
The nine-patient trial tested DX-88, a small protein discovered by Dyax that has specific affinity for the serine protease kallikrein, against hereditary angioedema, known as HAE and characterized by acute episodic attacks of subcutaneous, abdominal and/or laryngeal swelling.
"We're very committed to HAE being the way we get the product on the market first," said Sondra Henrichon, director of investor relations for Cambridge, Mass.-based Dyax.
"There's reason to believe kallikrein is a relevant target for other chronic inflammatory conditions as well, but we see this as the quickest path to approval," she added, noting the drug has been granted orphan drug status in the U.S. and Europe for that indication.
"Genzyme, of course, has built its reputation on marketing and [attaining] reimbursement for orphan drugs in niche products for small diseases you might not have heard of otherwise," Henrichon pointed out.
In March, Dyax said initial results showed the trial conducted in Europe met its primary endpoint. Henrichon said the company hopes to have the full data published, and another Phase II study is under way in the U.S. with 48 patients. The double-blind, placebo-controlled, dose-escalating trial is called Evaluation of DX-88's Effect on Mitigating Angioedema, or EDEMA1. The first of four dose cohorts in EDEMA1 is complete and the second cohort is in progress.
Under the joint-venture terms, the companies will split development costs for DX-88 in HAE from this point onward.
"Upon dosing the first patient in a pivotal Phase II trial, we'd receive a milestone of $3 million," Henrichon said. "Whether our EDEMA1 trial is pivotal remains to be seen, but we believe it could be."
Dyax would get another $10 million if DX-88 wins approval for HAE, and another $15 million if it's approved for a different chronic inflammatory indication.
"We have yet to decide what we'll pursue next," Henrichon said, but possibilities include end-stage liver disease due to cirrhosis and renal toxicity associated with high-dose interleukin-2 therapy.
DX-88 would be marketed by Genzyme, also of Cambridge, Mass., worldwide, and the companies would equally share profits from sales of DX-88 for HAE and/or other chronic inflammatory conditions.
Dyax has all rights to DX-88 in surgical indications, having exercised an option in March. A Phase I/II trial is under way for blood loss in coronary artery bypass graft surgery, Henrichon said.
But the first agreement between Genzyme and Dyax regarding the compound dates back to 1998, when the drug was known as EPI-KAL2. Genzyme made a $3 million equity investment in Dyax's private placement, extended a $3 million line of credit and pledged the potential milestones. (See BioWorld Today, Dec. 2, 1998.)
"There's always been an agreement in place that once we finished the first Phase II study, Genzyme would have the option of whether to buy in," Henrichon said.
Had Genzyme declined, "we probably would have chosen to move forward ourselves with it," she added. "The costs of conducting a clinical trial [with HAE] and the size that are required are manageable for a small company like Dyax."
Either way, the outcome for Dyax would have been favorable, Henrichon said, "but there's nothing like the validation of a company like Genzyme being in a JV for what we believe will be our first product to market."
Dyax's stock (NASAQ:DYAX) closed Tuesday at $4.28, up 28 cents. Genzyme's shares (NASDAQ:GENZ) ended the day at $42.79, up 5 cents.