Washington Editor

Partners Onyx Pharmaceuticals Inc. and Bayer Pharmaceuticals Corp. filed a new drug application for their much-anticipated oncology drug, sorafenib, triggering a $10 million milestone payment to Onyx in the process.

"We're very excited to file this first NDA in kidney cancer for sorafenib," Julie Wood, Onyx's vice president of corporate communications and investor relations, told BioWorld Today.

Should the FDA accept the filing and respond favorably, the companies expect to launch the drug in the first half of next year. Their submission is based on an ongoing Phase III trial, from which results were reported earlier this year at the American Society of Clinical Oncology meeting. Just two months before releasing those specific figures, the partners said they planned to file on interim data. (See BioWorld Today, March 22, 2005.)

"It was our intention to move as quickly as possible once we had favorable [progression-free survival] data from our Phase III international study," Wood said, noting that the trial was the largest such study ever done in kidney cancer patients.

Findings from the randomized, placebo-controlled trial showed that progression-free survival was doubled to a median value of 24 weeks in sorafenib patients compared to 12 weeks in placebo patients (p<0.000001). But Onyx's share value fell on the news, as some stock analysts wrote that the data weren't positive enough. Many were of the opinion that a potential competitor, Sutent (SU011248, from Pfizer Inc.), could prove better. (See BioWorld Today, May 17, 2005).

The FDA has included sorafenib in its Pilot 1 Program for continuous marketing applications, through which the agency is committed to examining each reviewable unit of the submission within a six-month time frame. Wood said a priority review was requested, and if granted, a regulatory response would be due early next year.

Onyx, of Emeryville, Calif., and Bayer Pharmaceuticals, of West Haven, Conn., entered their partnership 11 years ago. If sorafenib receives FDA approval, Wood noted that the filing wouldn't necessarily represent an endpoint in the partners' long collaboration but rather could be seen as a new beginning.

They equally fund the product's clinical program and marketing expenses in the U.S., where it would be co-promoted and generate a 50/50 profit split. In Europe, Bayer would handle sales and marketing responsibilities so it would receive a slightly higher profit percentage, while in Japan, Bayer will control all development and Onyx would receive a high single-digit royalty on sales.

Sorafenib, an oral small molecule, is a multi-kinase inhibitor that targets serine/threonine and receptor tyrosine kinases in both the tumor cell and tumor vasculature. Its pivotal kidney cancer trial began late in 2003 by way of a special protocol assessment with the FDA. Placebo patients already have crossed over to drug treatment based on the survival data, and all patients will continue to be treated and followed for survival. To date, 769 patients have been evaluated for safety and drug-related adverse events that include rash, diarrhea, hand foot syndrome, hair loss, itching, nausea, hypertension and fatigue.

In addition to that study, the investigational drug, also labeled BAY 43-9006, is available to U.S. patients through the Advanced Renal Cell Carcinoma Sorafenib (ARCCS) study. To be eligible, advanced kidney cancer patients cannot have been previously treated with sorafenib. A similar trial soon will start in Europe, and the partners are working with regulators on similar programs in other territories.

In previous preclinical models, sorafenib targeted members of two classes of kinases known to be involved in both tumor growth and blood supply, including RAF kinase, VEGFR-2, VEGFR-3, PDGFR-b, KIT, FLT-3 and RET.

The product also is being tested in Phase III in combination with carboplatin and paclitaxel for advanced metastatic melanoma patients, as well as in a Phase III study of liver cancer patients. Earlier-stage trials sponsored by the partners and the National Cancer Institute are testing sorafenib as a single agent and in combination therapy for additional oncology settings such as lung, ovarian, prostate and breast cancers. (See BioWorld Today, March 9, 2005, and May 16, 2005).

For Onyx, Wood said, the bulk of its focus going forward remains centered on "the excitement about sorafenib, not only the filing of this NDA, but also its potential in a wide variety of tumor types." On Monday, its shares (NASDAQ:ONXX) lost 36 cents to close at $26.42.

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