West Coast Editor

Kosan Biosciences Inc. is stopping its Phase II trial with KOS-862 in prostate cancer based on poor interim data, but the company's stock - possibly helped by investor hopes for an ongoing Phase II study with the compound in breast cancer - escaped damage.

The firm's shares (NASDAQ:KOSN) ended Tuesday at $6.24, down 1 cent.

"We didn't have all the data until fairly recently, so we didn't have expectations or lead anybody to expectations," said Daniel Santi, Hayward, Calif.-based Kosan's chairman and CEO, adding that "everybody has put their bets on the [breast-cancer] trials, would be my guess."

Kosan's decision to stop its Phase II study with KOS-862 for hormone-refractory prostate cancer was based on an early peek at data showing that response rates did not meet the primary endpoint, as measured by the change in prostate specific antigen levels, but the Phase II trial with the polyketide as a monotherapy against breast cancer continues to enroll patients.

The prostate-cancer study tested patients with advanced hormone-refractory disease who had previously progressed on docetaxel-based therapy. Patients got KOS-862 as single-agent therapy, with PSA response assessed every four weeks.

Although Kosan said results from the interim analysis showed the toxicity profile in the KOS-202 trial was "not dissimilar" to the profile observed in the Phase II trial with KOS-862 in non-small-cell lung cancer, a higher incidence of adverse events resulted in patient withdrawal in the prostate-cancer trial. Complete data from the study are expected in the first half of next year.

Working by the same mechanism of action as taxanes such as paclitaxel and docetaxel, KOS-862 also is being evaluated by Kosan and Roche in three Phase Ib combination studies with South San Francisco-based Genentech's breast-cancer drug Herceptin (trastuzumab), Gemzar (gemcitabine, from Eli Lilly and Co., of Indianapolis) and Paraplatin (carboplatin, from New York-based Bristol-Myers Squibb Co.).

The Kosan compound has an eventful history. In June 2004, a Phase II trial with KOS-862 against colorectal cancer was halted in favor of focusing on the prostate cancer indication, after research turned up some cumulative drug toxicities in patients previously treated with oxaliplatin (sold as Eloxatin by the Paris-based Sanofi-Aventis Group). Later in the year, Kosan terminated a Phase II non-small-cell lung cancer trial of KOS-862 when it yielded no tumor response. (See BioWorld Today, June 24, 2004, and Nov. 24, 2004.)

Now the prostate-cancer bid with KOS-862 is over, too, although Kosan's partner for the lead compound, Basel, Switzerland-based F. Hoffmann-La Roche Ltd., said the pharma firm has not lost faith in the epothilone class to which the drug belongs.

"KOS-1584, the backup [compound], is now in two Phase I trials," Santi noted.

Meanwhile, preliminary data from the Phase II trial with KOS-862 as a monotherapy against breast cancer have been accepted for presentation at the San Antonio Breast Cancer Symposium in December, and the Phase Ib portion of a study testing KOS-862 plus Herceptin has finished patient sign-ups. The Phase II part of that trial is expected to start enrolling this quarter.

"I think we have a drug here," Santi said.

Roche and Kosan signed their potential $220 million global deal for epothilones in the fall of 2002, with Roche getting worldwide exclusive rights to market and sell KOS-862 and epothilone analogues owned by or licensed to Kosan for cancer. Kosan is co-developing and has the right to co-promote in the U.S. (See BioWorld Today, Sept 24, 2002.)

"That's been extremely good for us, in terms of the up front we got," as well as financial sponsorship of studies, he said.