Washington Editor

Confusion surrounding Phase III data for a myelodysplastic syndrome candidate named Dacogen caused SuperGen Inc.'s stock to dive, despite the firm's contention that the data are positive.

In a conference call after the market closed Wednesday, SuperGen officials said the Phase III trial hit the primary endpoint of delaying either progression to acute myelogenous leukemia or death.

But in response to two different "p" values derived from the trial, SuperGen's stock (NASDAQ:SUPG) fell $4.24 Thursday, or 33.1 percent, to close at $8.56.

Indeed, patients randomized to the Dacogen arm had an increased time to progression to AML or death (p=0.042 Wilcoxon test, p=0.198 log-rank test), compared to patients randomized to supportive care only. Median time to progression to AML or death in Dacogen patients was 338 days vs. 263 days in patients on supportive care.

"This mixed outcome on the primary endpoint caused the pressure on the stock, coupled with a not-so-clear explanation on the conference call of why they used two [tests]," Elemer Piros, senior biotechnology analyst with Rodman & Renshaw Inc. in New York, told BioWorld Today. "The conference call was going on for about an hour and a half and people were still walking away with some degree of confusion."

Company officials were not available for comment Thursday. However, James Manuso, SuperGen's president and CEO, released a statement saying the firm is pleased with the study and anticipates completing submission of its rolling new drug application in the third quarter.

At the heart of the matter is the fact that the Wilcoxon test was positive, while the log-rank test failed.

"The conclusion of some people would be that after seeing the failure of the log rank, they picked another statistic," Piros said. "This wasn't the case. At the outset, they specified that they would use two different statistical measures and would see whether either or both showed statistical significance. Unfortunately for them, only one came up positive."

Dacogen (decitabine), a cancer candidate, reverses DNA hypermenthylation. SuperGen's Phase III study enrolled 170 patients at 22 North American sites, with 89 randomized to Dacogen plus supportive care and 81 randomized to supportive care only. Supportive care included antibiotics, growth factors and/or transfusions.

The overall response rate for patients randomized to Dacogen was 22 percent (nine complete responses and 11 partial responses) compared to 0 percent in patients on supportive care only (p<0.001, Fisher exact test).

Release of the data comes on the heels of a recent slip-up by a SuperGen scientific advisory board member who inadvertently disclosed favorable interpretive analysis related to Kaplan-Meyer curves in the Phase III during a conference call in early March, sending the firm's stock soaring $1.58, or 24.1 percent, to close at $8.15. (See BioWorld Today, March 11, 2004.)

Piros, who was on that conference call, said the incident fueled enthusiasm about the drug, which he believes will make it to market.

The FDA is expected to rule on Dacogen six to nine months after Pharmion Corp.'s Vidaza (azacitidine for injectable suspension), also a proposed treatment for myelodysplastic syndromes, enters the market.

While they are members of the same drug class, Dacogen and Vidaza are different chemical entities and each has been granted orphan status, an FDA seven-year market exclusivity guarantee. Piros believes the drugs will split the $500 million U.S. market in MDS. Dacogen likely would pick up another 30 percent to 50 percent in off-label use in sickle cell anemia and other leukemias, he said.

Vidaza's fate could provide an insight into Dacogen's future, Piros said, adding that Pharmion's data demonstrated that 22 percent to 23 percent of patients taking Vidaza would enter complete or partial remission. (Dacogen data are the same.)

"What SuperGen has may be better because they have the response and they have an OK indication that this response will translate to clinical benefit - and that's time to leukemia/time to death," Piros said.

Pharmion filed its application in December, and expects action June 29. Meanwhile, SuperGen expects to file later this year, according to Piros, who believes the rolling NDA will be complete by late September, meaning the firm could expect FDA action in one year.

Piros said SuperGen and Vidaza are similar drugs studied in similar trials in the same indication.

"You could make the argument that these are both weak applications and both will be shot down," he said. "I don't think that is likely. There are no other approved therapies out there and the evidence for going into complete and partial remission is very, very strong, and the FDA would find it very difficult to ignore that evidence."

MDS is a cancer of bone marrow that often is fatal. Some cases progress to leukemia.