West Coast Editor

Effectively handicapping themselves in the race with Pfizer Inc. to get a kidney cancer drug to market, Onyx Pharmaceuticals Inc. and Bayer Pharmaceuticals Corp. said they plan to pursue FDA clearance of their drug based on results from an ongoing Phase III trial rather than data gleaned from the Phase II study.

Richmond, Calif.-based Onyx's stock (NASDAQ:ONXX) lost a third of its value, closing Monday at $27.34, down $13.47.

"The company has never guided for approval on the Phase II data, but they said it was possible," noted David Witzke, analyst in the New York office of SunTrust Robinson Humphrey. "We thought they had a chance but it wasn't something we'd count on."

The companies said data from the recently completed Phase II trial will be used to support the Phase III results, which are not yet available. If all goes well, the partners expect to launch BAY 43-9006 - an orally active inhibitor of the enzyme Raf kinase and vascular endothelial growth factor receptor - in 2006.

About a year ago, Onyx and Bayer, of West Haven, Conn., a subsidiary of Leverkusen, Germany-based Bayer AG, hailed the positive interim Phase II data when they disclosed the Phase III program would begin. (See BioWorld Today, Oct. 28, 2003.)

Data disclosed Monday focused on the 502 patients enrolled in the study, 202 of whom were advanced kidney cancer patients with progressing disease upon study entry.

After 12 weeks of treatment with BAY 43-9006, 65 patients with stable disease were randomized to receive placebo or BAY 43-9006. After a subsequent 12-week treatment period, there was a statistically significant higher percentage of participants whose disease did not progress in the BAY 43-9006 group, compared to those never randomized to placebo.

Based on investigator assessments, 70 percent of study participants with kidney cancer had tumor shrinkage or disease stabilization. Along with the 65 randomized patients with stable disease, 79 kept getting the drug on an open-label basis.

Investigators found the time to tumor progression was 169 days for the entire kidney cancer population (including placebo patients). In control groups of similar studies, time to progression has been about 60 days to 90 days.

As long ago as July, Bayer noted in its handout to investors that the drug partnered with Onyx likely would not be launched until 2006 (and positive interim Phase III data could move up approval to late 2005). Still, the unlikelihood of filing on Phase II data was the bigger factor in the trouncing delivered to Onxy's stock, Witzke told BioWorld Today.

Adding to the somewhat-complex picture is the fact that the Phase II trial, although it showed some tumor shrinkage, was geared to show stabilization - so characterizing the results as "mixed" (as some reports did) might be misleading. The trial, after all, did meet its primary stabilization endpoint.

But the response rate as first reported by investigators was 12 percent, Witzke pointed out, "and the final response rate with independent review was 4 percent. How that number changed could have been viewed negatively by some investors."

Those response rates could affect how the Onyx/Bayer drug competes in the kidney cancer marketplace. New York-based Pfizer's drug is SU011248 (brand named Sutent), a multitargeted tyrosine kinase inhibitor originally from Sugen Inc. The compound, like BAY 43-9006, is in Phase III trials, and the pair appear due for a tight race.

"The Pfizer data have been impressive, with a 33 percent response rate and 8.3 months time to progression in second-line patients," Witzke said. "The one concern has been tolerability. There's a lot of fatigue, but it appears they can manage it in some cases with dose reduction."

Also in the running against kidney tumors is the approved drug for colorectal cancer Avastin (bevacizumab). In June, South San Francisco-based Genentech Inc. and OSI Pharmaceuticals Inc., of Melville, N.Y., said Phase I/II data of Avastin with Tarceva (erlotinib) to treat metastatic renal-cell carcinoma and relapsed non-small-cell lung cancer showed that 21 percent of patients experienced an objective response and 66 percent experienced a minor response and disease stabilization. Overall survival after six months was 92 percent.

"Most of the data we've seen is first-line data, and the data with Tarceva are quite interesting because [the drug] appears to be better than either agent on its own," Witzke said.

Also, a Phase III trial called CALGB 90206 is designed to test overall survival, time to disease progression and objective response rates in patients with advanced renal-cell carcinoma when treated with interferon alfa-2b, with or without Avastin, though experts consulted by SG Cowen & Co. in New York opined in the spring that the Onyx and Pfizer drugs would prove better against kidney cancer. (See BioWorld Today, May 24, 2004.)

Data from that trial are expected in the first half of 2006.

How BAY 43-9006 might fit in with the others for kidney cancer remains to be seen.

"It's early and they're still trying to learn where they'll use these drugs," Witzke said.