About one month ahead of disclosing Phase II data for DX-88 in hereditary angioedema, Dyax Corp. said the FDA has placed the compound on clinical hold pending answers to the agency's questions regarding animal studies.
Since the hold, the company has provided more data, and on Monday spoke with the FDA. Henry Blair, chairman, president and CEO of Cambridge, Mass.-based Dyax, said the company could hear back from the agency in "perhaps as soon as two weeks."
Although the hold affects just one trial in progress, Dyax's stock (NASDAQ:DYAX) dropped more than 28 percent on the news, or $4.15, to close Tuesday at $10.26. It had dipped as low as $9.20. In the stopped trial, called EDEMA2, 12 attacks of angioedema have been treated so far, with no adverse affects.
At issue is "a small number of sporadic deaths" in rats during routine preclinical repeat-dosing toxicity studies, in animals given doses about 12 times higher than any dose ever given a human - and 36 times higher than the dose given in EDEMA2.
Gregory Wade, analyst with Pacific Growth Equities LLC in San Francisco, noted the rat problems are "not at all indicative of clinical experience," and told BioWorld Today his "sense is that the company will be able to overcome this [delay] very quickly." Wade owns no Dyax shares, though his firm makes a market in the company and has done investment banking for it.
Dyax has provided primate data to the FDA, which showed no deaths or other evidence of toxicity, plus a summary of results of all trials thus far in humans, including outcomes from 139 doses administered to 105 patients. Results of the EDEMA1 Phase II trial, which involved 48 patients, will be disclosed publicly in June, the company said.
Thomas Shrader, director of health care equity research with Harris Nesbitt Gerard in New York, noted during a conference call with Dyax that DX-88 has proved "remarkably non-antigenic for an engineered protein," and asked if the company has any clues about the rat deaths.
"There was no pathology associated with the deaths of these rats," Blair said. "In fact, the study reports came back saying it was non-drug related, but it is enough to be of concern." Results have been examined three times by Dyax scientists, he added.
"We give this to rats in a slow bolus, unlike we do in humans, which is a 10-minute infusion," Blair said, and duplicating the human method in rats is not possible because of the drug's half-life.
"If you give it very rapidly [in the rats] and give a very high spike, you may have just simply a protein effect" causing the deaths, he said. "Some died after the 13th exposure, some died after the first exposure, so it's not clear what's going on."
DX-88 is being developed for angioedema in a joint venture with Genzyme Corp., also of Cambridge. Its stock (NASDAQ:GENZ) ended Tuesday at $43.31, up $1.23.
Separately, Dyax is developing the protein for patients undergoing on-pump coronary artery bypass grafting surgery (CABG). No trials are active in that indication, but positive initial Phase I/II data from a 42-patient study were disclosed in December. The company said it's optimistic that Phase II CABG studies will start in the second half of this year.
Meanwhile, Blair said, "I'm not sure we have to do anything further [regarding the FDA's query on the rat deaths], if you want to know the truth." Along with animal results, "we provided them with some of the human data, which they had not received in the past," he said. "They have agreed to work with us expeditiously in coming to a conclusion on this."