Washington Editor

SuperGen Inc. on Tuesday said it submitted the first component of its new drug application for Dacogen, an investigational agent for the treatment of myelodysplastic syndromes.

The chemistry, manufacturing and controls (CMC) were the first part of the rolling submission, as per an agreement between the company and the FDA reached in April. SuperGen, of Dublin, Calif., expects to complete the submission in the third quarter.

Dacogen (decitabine), a cancer candidate that reverses DNA hypermethylation, has been granted FDA fast-track status.

Officials at SuperGen could not be reached for comment.

The FDA describes myelodysplastic syndromes, or MDS, as a collection of disorders in which the bone marrow does not function normally and not enough normal blood cells are made. MDS might develop following treatment with drugs or radiation therapy for other diseases, or it might develop without any known cause. Some forms of MDS can progress to acute myelogenous leukemia (AML), a type of cancer in which too many white blood cells are made. About 20,000 to 30,000 new cases are diagnosed in the U.S. each year.

Treatment options were slim until a few days ago when Boulder, Colo.-based Pharmion Corp. won FDA approval of Vidaza in five MDS subtypes, including refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation and chronic myelomonocytic leukemia. (See BioWorld Today, May 21, 2004.)

While they are members of the same drug class, Dacogen and Vidaza (azacitidine for injectable suspension) are different chemical entities and each has been granted orphan status, an FDA seven-year market exclusivity guarantee. The worldwide market is estimated at $1.3 billion. Also, Celgene Corp., of Warren, N.J., is developing an MDS candidate called Revimid.

As for Dacogen, SuperGen ran into a bit of a problem in Wall Street's eyes on releasing Phase III data in April. SuperGen's stock fell 33.1 percent to close at $8.56 when the company released a mixed outcome on the primary endpoint. (See BioWorld Today, April 2, 2004.)

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.

At the time, an analyst said the mixed outcome on the primary endpoint as well as an unclear explanation as to why SuperGen used two tests caused the stock to fall. SuperGen maintained that it hit the primary endpoint of delaying either progression to AML or death.

The Phase trial III 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 zero percent in patients on supportive care only (p<0.001, Fisher exact test).

SuperGen's stock (NASDAQ:SUPG) fell 25 cents Tuesday to close at $7.32.

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