Washington Editor

BETHESDA, Md. - Panel members recommended approving Tarceva (erlotinib) for pancreatic cancer, siding with the drug's developers and against criticism from the FDA.

The agency's Oncologic Drugs Advisory Committee voted 10-3 on the side of approving the tyrosine kinase inhibitor of EGFR, for which OSI Pharmaceuticals Inc. has submitted a supplemental new drug application. The Melville, N.Y.-based company is seeking clearance for 100 mg of Tarceva plus gemcitabine (Gemzar, from Eli Lilly and Co.) as a first-line treatment in patients with locally advanced, unresectable or metastatic pancreatic cancer.

"I think the winners are patients with pancreatic cancer," Pablo Cagnoni, OSI's vice president of medical affairs and translational research, told BioWorld Today. "They have one more option now, physicians have one more option in their arsenal, and I think we showed clearly that Tarceva improves the standard of care."

Supporting its application, the company's speakers stressed the statistically significant survival benefit its product demonstrated in a single two-year study. Those data point to a 25 percent increase in survival, said Gary Clark, the company's vice president of biostatistics and data management, based on a 0.80 hazard ration (p=0.018). OSI first had presented those survival data a year ago. (See BioWorld Today, Sept. 21, 2004.)

"We can debate all day whether the magnitude of that benefit is enough," Cagnoni said, "but we think it's a step forward and the committee thinks it's a step forward, and we look forward to getting this into the hands of physicians."

Committee members voted 13-0 that Tarceva's survival effect was statistically persuasive, and 11-2 in favor of the data's clinical importance. The FDA, which has until Nov. 2 to decide on the application, argued at the meeting against approval, largely because its investigators said the drug's risks outweighed the benefits.

In contrast, public input at the committee meeting condemned the agency for minimizing the value of extending lives among cancer patients already burdened with a dim outlook - a 99 percent mortality rate, which one speaker characterized as a "virtual death sentence." Such sentiments were echoed by a committee member, the University of Southern California's Alexandra Levine, who said the FDA should not ignore "an improvement of one month over" the six-month prognosis given most pancreatic cancer patients.

Other supporters said such an advantage should not be ignored. "The combination of Tarceva and gemcitabine represents an important treatment option for patients and physicians who want a more aggressive, more effective treatment for pancreatic cancer," said Mace Rothenberg, a professor of medicine at the Vanderbilt Ingram Cancer Center, who addressed the panel on behalf of the company. Boston University's Ralph D'Agostino, a committee member, added that the "survival is extremely impressive."

The FDA typically follows the advice of its panels, though the agency's chief investigator, Adrian Senderowicz, was resolute in his criticism of Tarceva.

He said the 12 extra days of median survival benefit conferred by the drug was of "questionable clinical benefit," especially in light of the drug's increased risks. He noted that links to strokes "were a significant concern," given an incidence rate of 2.3 percent in the Tarceva arm compared to zero in the placebo arm, as well as other cardiovascular complications, interstitial lung disease and additional side effects. The agency also charged that there were no clinically meaningful differences in response rate, duration of response or progression-free survival. In concluding, Senderowicz said Tarceva adds "marginal efficacy" while increasing "severe toxicity."

While the committee voted against that advice, his assessment still resonated with many of its members who recommended Phase IV studies to better evaluate Tarceva's benefit in the setting. Others, led by committee Chair Silvana Martino, of the University of Southern California, also expressed concerns over licensing sales of a drug on the basis of a single pivotal study. But the panel voted 12-1 against recommending another confirmatory trial.

A day before the hearing, a briefing document released by the FDA criticized the lack of a second, supportive trial and outlined other concerns of OSI's application, causing the company's stock to slump lower than it has in a year. (See BioWorld Today, Sept. 13, 2005.)

The drug's supplemental new drug application was filed at the end of April. It is partnered with South San Francisco-based Genentech Inc.

Also at the panel meeting, committee members voted 13-0 against a prostate cancer drug, Xinlay (atrasentan, from Abbott Laboratories). The Abbott Park, Ill.-based company had applied for approval in patients with bone metastases, though the drug had failed to achieve its primary endpoint in a Phase III study.

Today, the same panel will vote on Revlimid (lenalidomide, from Celgene Corp.), a product for myelodysplastic syndromes, and Arranon (nelarabine, from GlaxoSmithKline plc), a drug for leukemia and lymphoma.

On Tuesday, OSI's shares (NASDAQ:OSIP) gained $1.41 to $32.15, making up most of the $1.56 the stock lost Monday.

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