West Coast Editor

Bad tidings from the FDA regarding SuperGen Inc.'s Orathecin for pancreatic cancer overshadowed positive (if expected) news about the company's Dacogen for myelodysplastic syndromes, partnered with MGI Pharma Inc.

In separate developments disclosed Monday, SuperGen said the regulatory agency found that data submitted by the firm did not support approval of Orathecin (rubitecan), and the company withdrew its new drug application, but the FDA accepted for filing the NDA related to Dacogen (decitabine).

SuperGen's shares (NASDAQ:SUPG) ended Monday at $6.10, down more than 13 percent. Tuesday's closing bell left shares at $5.84.

Although withdrawing the Orathecin NDA at such an advanced stage of the regulatory process was an "extremely difficult decision for us to make," it was the right thing to do, said James Manuso, president and CEO of Dublin, Calif.-based SuperGen, in a conference call Monday.

"Last week, during an informal phone call with the FDA, we were advised that the review was nearing completion," he said. "[The] FDA cannot, of course, give a sponsor direct information into their plan of action, but they offered no new or alternative approaches for a successful conclusion of the Orathecin NDA."

External consultants provided their views, SuperGen's senior management held a meeting, and the board of directors convened. The day before New Year's Eve, the company decided the "most prudent" course would be to withdraw the NDA and then review the FDA's findings of deficiency, which are due this quarter, to determine the best way to proceed, Manuso said.

Pulling the NDA "in no way predisposes the FDA negatively to a future resubmission," he noted.

The company plans to keep trying for European approval of Orathecin and still plans to try it against pancreatic cancer in a Phase III trial combined with gemcitabine (Gemzar, Eli Lilly and Co.).

The European request for clearance was submitted July 1, and usually takes about 12 months for a decision, Manuso said, adding that the overseas regulators "may take a more clinical rather than statistical approach to the Orathecin data and will therefore favorably assess the limited but very real clinical benefit inherent in this drug."

Backing the NDA for Orathecin were results from a 409-patient Phase III trial that compared Orathecin to the most appropriate chemotherapy or physician's choice in patients who failed other treatments. Although the study missed the primary survival endpoint, secondary endpoints of time to disease progression and response were achieved. Not enough, the FDA said. (See BioWorld Today, Jan. 28, 2004.)

Orathecin is a topoisomerase I inhibitor extracted from the bark and leaves of China's Camptotheca acuminata tree.

Acceptance of the Dacogen NDA, on the other hand, represents something of a vindication for SuperGen, which faced investor skepticism and a 33 percent stock plunge in the spring, when Phase III data were disclosed. (See BioWorld Today, April 2, 2004.)

At the time, SuperGen offered two differing "p" values, which apparently confused Wall Street. Still, patients randomized to the Dacogen arm of the study showed increased time to progression to acute myeloid leukemia or death (p=0.042 in the Wilcoxon test; p=0.198 in the log-rank test), compared to those randomized to supportive care only. Median time to progression to AML or death in patients given Dacogen, which is designed to reverse DNA hypermethylation, was 338 days vs. 263 days in patients on supportive care.

Minneapolis-based MGI, the Dacogen partner, pocketed a $1 million milestone payment as a result of the NDA's acceptance for review.

Some might have hoped the FDA would grant Dacogen expedited (six-month) review, but that's generally allowed to drugs targeting indications for which nothing is approved. For myelodysplastic syndrome, Vidaza (azacitidine) gained FDA clearance in May. The compound from Pharmion Corp., of Boulder, Colo., is an anti-neoplastic pyrimidine nucleoside analogue. Dacogen's regular review cycle puts the due date for a decision at Sept. 1.

Christopher Raymond, analyst with Robert W. Baird & Co. in Chicago, pointed out in a research report there's been no head-to-head comparison of Dacogen with Vidaza, but the former's 17 percent overall response rate falls in line with Vidaza's label, which boasts a 16.2 percent rate. Raymond modeled launch of Dacogen for 2006, estimating revenue at $29 million.

Rodman & Renshaw in New York reiterated its "market outperform" rating on SuperGen in a research note Monday, but lowered the target price from $21 to $17.

No Comments