Less than two months after filing a new drug application for Tarceva to treat non-small-cell lung cancer, Genentech Inc. and OSI Pharmaceuticals Inc. started a Phase IIIb study of the drug.

The multicenter, open-label study, called ACT (Access to Care, Tarceva), is not being done to supplement the NDA, but rather to provide some hope for patients who have already failed previous regimens.

"This is a method by which patients can access the drug while we're awaiting the FDA decision," said Colleen Sweeney, spokeswoman for South San Francisco-based Genentech.

As the first targeted therapy to show a survival improvement in advanced NSCLC patients, Tarceva (erlotinib HCl) offers another option to patients who have previously received chemotherapy. ACT will evaluate a once-daily oral dose of Tarceva as it focuses on the endpoints of survival and response rate. It will enroll a patient population consistent with the pivotal Tarceva trial in which the NDA is based. That trial enrolled 731 patients.

"The patient population will be similar to the pivotal study," Sweeney told BioWorld Today, "but there's no enrollment cap, so the study will be open until there's an FDA decision."

That decision is expected to come early next year, assuming a six-month fast-track review. If approved, it would be marketed in the U.S. by Melville, N.Y.-based OSI and South San Francisco-based Genentech, with the profits being equally shared. Genentech would take the lead role in marketing the product, while OSI would provide manufacturing. The product is partnered overseas with Basel, Switzerland-based F. Hoffmann-La Roche Ltd., which submitted a marketing authorization application in Europe in August for Tarceva.

OSI filed the NDA in July for Tarceva as a monotherapy for patients with advanced NSCLC after failure of at least one standard chemotherapy regimen. The FDA gave Tarceva Pilot 1 status under its program for Continuous Marketing Applications, which is designated for products with fast-track status that have demonstrated significant promise in clinical trials as an advance over available therapies. (See BioWorld Today, Aug. 3, 2004.)

Tarceva is designed to block tumor cell growth by inhibiting the tyrosine kinase activity of the epidermal growth factor receptor, thereby blocking the HER1/EGFR signaling pathway inside the cell.

"There are a couple of things that are unique about Tarceva," Sweeney said. "The first is it's a small molecule, so it's a pill that patients take every day, which is convenient. Second, the pivotal trial showed a survival improvement in these patients, and this was for those that already have failed a chemotherapy regimen."

The double-blind, placebo-controlled pivotal Phase III trial compared Tarceva to placebo. Tarceva improved median survival by 42.5 percent. The survival improvement was 4.7 months in patients in the control arm, compared with 6.7 months in patients treated with Tarceva.

Adverse events found in the Tarceva group included mild to moderate rash and diarrhea, prompting researchers to lower the Tarceva dose. More serious pulmonary events, including potential cases of interstitial lung events, appeared infrequently and were equally distributed between the treatment arms.

The results were presented in June at the 40th Annual American Society of Clinical Oncology meeting in New Orleans. (See BioWorld Today, June 8, 2004.)

There are more than 1.2 million cases worldwide of lung and bronchial cancer each year, according to World Health Organization data. In the U.S., it is the largest cause of cancer deaths, accounting for 30 percent of them. NSCLC accounts for almost 80 percent of all lung cancer occurrences.

Aside from Tarceva, Genentech is focused on various cancer products, including its three marketed therapies, Rituxan, Herceptin and Avastin. It markets Herceptin and Avastin on its own, but co-markets Rituxan with Biogen Idec Inc., of Cambridge, Mass. Roche has rights to all three products outside of the U.S. In early development, the company is working on a Phase II therapeutic antibody, a small molecule directed at the hedgehog pathway, and a humanized anti-CD20 antibody for hematology/oncology indications.

OSI exclusively markets Novantrone for oncology and Gelclair for pain associated with oral mucositis. It also is developing a liposomal product designed to mimic a long-term infusion of 5-FU and a co-inhibitor of c-Kit and vascular endothelial growth factor.

The company's stock (NASDAQ:OSIP) dropped 1 cent on Friday, to close at $60.43. Genentech's stock (NYSE:DNA) rose 77 cents, to close at $49.85.

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