West Coast Editor
Finding itself in the news once again was DX-88, the Phase II drug for hereditary angioedema from Genzyme Corp. and Dyax Corp., with both companies taking part in a conference call to clarify remarks made during Genzyme's earnings call last week.
Dyax's stock (NASDAQ:DYAX) ended Monday at $8.25, down 2 cents. A serious hit came in May when the stock lost more than 28 percent, or $4.15, to close at $10.26, after the FDA placed DX-88 on clinical hold pending answers about rat toxicity studies. (See BioWorld Today, May 26, 2004.)
That issue was resolved last month, when Dyax disclosed that the clinical hold had been lifted, and its stock was lifted, too, back up to $12.96. Monday's conference call dealt mainly with questions regarding market demand for DX-88. Dyax's chairman and CEO, Henry Blair, said questions and answers during the Genzyme earnings call had "resulted in some confusion in the marketplace."
Hereditary angioedema, or HAE, is an immune system disorder caused by the lack of a protein, the C1 inhibitor, which affects blood vessels and leads to attacks of sudden swelling of the hands, feet, limbs, face, intestinal tract, or airway (larynx or trachea).
In the U.S., DX-88 could help 3,000 to 5,000 patients identified, said Paul Merrigan, vice president of global marketing at Cambridge, Mass.-based Genzyme, and "we're seeing equal to or even more patients that have already been identified in Europe."
Numbers are extrapolated from current HAE patients, he added. Since HAE is an autosomal-dominant disease, when one patient is found, typically several more are found in the family. In total, the companies estimate that there are between 13,000 and 66,000 patients with HAE in the U.S. and Europe.
Blair noted that autosomal dominance "means one-half of the offspring of any HAE patient has an equal chance of having the disease or not having the disease. Certainly one can go both down the family tree and back up the family tree and find other patients, which is unlike something such as Gaucher's disease," for which Genzyme markets Cerezyme (imiglucerase for injection).
Being able to guess accurately about patient numbers, Merrigan said, "puts us at a tremendous advantage at this stage in our development," in terms of market research.
Analysts during the conference call particularly were interested in how many attacks HAE patients tend to have in a year. Dyax, also of Cambridge, and Genzyme earlier put the number at an average of 12. Richard Moscicki, chief medical officer and senior vice president at Genzyme, said he was "glad that I have the opportunity to comment on that, because I was concerned that perhaps my comments were not understood in their entirety."
Moscicki stuck with 12, but said "the number of attacks are quite variable" and "probably represents a degree of under-reporting." An association for HAE patients recently conducted a survey that found that "even on steroids, these patients may be having much more than the 12 attacks we have seen in the untreated patients."
He said physicians and patients "have made it very clear to us they are extremely eager to have that opportunity to move away from steroids and have this kind of therapy available for them. There is a real hunger for this approach, so we continue to feel comfortable, when putting together marketing instruments, that the number 12 is a very reasonable number to be working with."
Anthony Williams, senior vice president of medical affairs and clinical operations at Dyax, noted that any of those episodes could turn into the potentially deadly laryngeal attack. Results with DX-88 apparently depend on how quickly the patients are treated, he said.
"If it's within four hours of the start of the attack, the responses have been uniformly very encouraging, with people starting to have responses in 30 minutes and the attack being terminated within the four-hour study period that we normally look at," he said. "So we are gathering quite a large series of laryngeal cases. If you catch the attack before it becomes established, the responses at the moment seem exceptionally good."
Of 14 attacks studied so far - taken from the completed EDEMA 1 Phase II trial, the ongoing EDEMA 2 trial and compassionate-use studies - "12 were what I call attacks you can actually assess," Williams said. "In other words, they came in within four hours of having the attacks start and had the infusion. They all responded very rapidly." He called the evidence "pretty compelling."
Blair said the number of laryngeal attacks the companies end up treating "may, in fact, have some impact when we actually talk to the FDA" about making the ongoing Phase II trial a pivotal study.
"That trial is actually geared to treat up to 240 [attacks], and the reason we've gone that high is that we want to continue to treat these patients right through to approval," he said. "We certainly don't want to have to stop the trial and take people off a safe and effective drug before the drug is actually approved."
Discussions are ongoing with the FDA regarding when all required testing might be finished.
"We hope to have an answer for you on that during our earnings call, which will be the first week in August," Blair told investors.
Genzyme's stock (NASDAQ:GENZ) closed Monday at $48.86, down 89 cents.