West Coast Editor

One of the hotter kidney cancer drug candidates was the subject of good news, as Onyx Pharmaceuticals Inc. and Bayer Pharmaceuticals Corp. said a planned interim review of data from the Phase III study with sorafenib led them to recommend all patients enrolled in the trials get the drug.

Bennett Weintraub, analyst with Hibernia Southcoast Capital in New Orleans, said his firm "already had a 74 percent probability of approval, and I would say that was more cautious than many people, who would say this drug has made it." The latest development, he said, is "icing on the cake."

Wall Street seemed to agree, pushing Onyx's stock (NASDAQ:ONXX) up $1.61 Monday to close at $31.61.

Interim data show patients given sorafenib (formerly BAY 43-9006) achieved a clinically significant improvement in the duration of disease stabilization, defined as progression-free survival. After consulting with the independent data monitoring committee (DMC), the companies talked with investigators, who will offer the drug to all patients.

The multinational, placebo-controlled study recently finished enrolling more than 800 patients with advanced kidney cancer, randomized to get either sorafenib or placebo. The primary endpoint of the pivotal study is overall survival, with progression-free survival, overall response rate and safety also to be examined.

Onyx and Bayer, a subsidiary of Bayer AG in Leverkusen, Germany, started the trial in the fourth quarter of 2003 under a special protocol assessment plan with the FDA, and interim results from the study will be presented at the American Society of Clinical Oncology meeting in mid-May in Orlando, Fla. The firms already have said they intend to file for approval based on interim data, and new drug application paperwork is under way. (See BioWorld Today, March 22, 2005.)

As long ago as last spring, experts were making kidney cancer comparisons between sorafenib, a vascular endothelial growth factor (VEGF) inhibitor and RAF kinase, and the VEGF-binding monoclonal antibody Avastin (bevacizumab), from South San Francisco-based Genentech Inc., which is approved for colorectal cancer. (See BioWorld Today, May 24, 2004.)

A scientist queried by S.G. Cowen said sorafenib looks strong beside Avastin and seemed nearly on par with SU011248, the multi-targeted tyrosine kinase inhibitor from Sugen Inc., a unit of Pfizer Inc.'s Pharmacia Corp., against which the Bayer-Onyx compound is involved in a race to market. Sorafenib has orphan drug status in the U.S. and Europe.

But Weintraub said "people aren't thinking enough about Avastin in that indication," and pointed out that Avastin, alone and with Tarceva (erlotinib) - the epidermal growth factor inhibitor for non-small-cell lung cancer from OSI Pharmaceuticals Inc., of Melville, N.Y. - has "generated some very nice data in kidney cancer."

Weintraub called Avastin "more promising" than the Onyx/Bayer drug, but predicted the compounds likely will not be direct competitors.

"Avastin probably works in combination with any number of other drugs, including the Sugen drug and the Bayer and Onyx drug, as well," he told BioWorld Today. A bigger question is how serious a competitor Sugen's drug will be against sorafenib, and Weintraub said they would contend "more commercially than medically. It comes down to economics, and what the doctor would be more likely to prescribe."

But there's an even larger, near-term question. Drugs for kidney cancer in the past have come up with satisfying data in progression-free survival, like sorafenib's, but afterward fizzled in overall survival. Given that - along with the recent Tysabri embarrassment and others - Onyx and Bayer might confront a more skeptical FDA when asking for approval based on interim results.

Weintraub stood by his 74 percent probability, formulated even before Monday's news, which boosted sorafenib's chances of ultimate approval.

"If the [Phase III data to be disclosed at ASCO] are so blow-your-socks-off good that it just doesn't matter, the FDA could approve it" and ask for follow-up studies, as with Tysabri (natalizumab), he said. That drug, an alpha-4 antagonist for multiple sclerosis from Cambridge, Mass.-based Biogen Idec Inc. and Elan Corp. plc, of Dublin, Ireland, recently was pulled from the market after patients developed often-fatal progressive multifocal leukoencephalopathy.

On the other hand, Weintraub allowed, "the FDA could ask them to go all the way" with the Phase III trials and wait for overall survival data. The latest news "certainly bodes well for the outcome of the trial, but doesn't address whether there's a bubble in the survival [rate]. If they unblind the whole study, they might not be able to answer that question."

Julie Wood, spokeswoman for Emeryville, Calif.-based Onyx, told BioWorld Today the companies will continue the trial to its end, allowing patients to cross over to sorafenib, but have not disclosed whether they will unblind the whole study and "wouldn't take that step without consulting with clinicians, the DMC and regulatory authorities."

Meanwhile, Onyx has all of its chips on sorafenib. Weintraub called the compound "an important new drug, an oral medicine with a limited side effect profile. The company really has ceased to do anything but develop this drug, and Bayer is doing most of that."

Though sorafenib is the main reason to own the stock, another reason might be that Bayer will take what some view as the next logical step and buy out Onyx, which sharply reduced staffing and restructured in 2003 after the loss of Warner-Lambert Co., now part of Pfizer, which was Onyx's partner for the cancer drug ONYX-015, a modified adenovirus. (See BioWorld Today, Jan. 28, 2003, and Sept. 18, 2003.)

"It's mainly this partnership that keeps [Onyx] going as a company," Weintraub said.