Roche and Kosan to Initiate Phase 2 Cancer Development Program Roche and Kosan to Initiate Phase 2 Cancer Development Program With Epothilone R1645 (KOS-1584)
Tuesday February 27, 6:00 am ET
BASEL, Switzerland and HAYWARD, Calif., Feb. 27 /PRNewswire-FirstCall/ -- Roche and Kosan Biosciences Incorporated (Nasdaq: KOSN - News) announced today that the companies have selected their second-generation epothilone R1645 (KOS- 1584) to advance into a Phase 2 clinical development program exploring clinical activity and safety in multiple solid tumor types. While the first- generation compound R1492 (KOS-862) demonstrated meaningful objective response rates in metastatic breast cancer and non-small cell lung cancer, the companies have decided to discontinue its development and focus resources on advancing R1645.
As a second-generation epothilone R1645 is designed to have greater safety, efficacy and an enhanced pharmaceutical profile. In Phase 1 dose escalation trials, R1645 was well tolerated and demonstrated antitumor activity against ovarian and non-small cell lung cancers. On the basis of R1645's tolerability and antitumor activity in multiple tumor types, Roche and Kosan have agreed to rapidly advance this compound into later-stage development.
"Phase 1 results encouraged us to support the expanded clinical development of R1645," said Peter Hug, Global Head of Pharma Partnering for Roche. "We look forward to working further with Kosan on the Phase 2 program exploring the therapeutic potential of R1645 in multiple solid tumor types."
"R1645 (KOS-1584) combines the optimal properties of Kosan's proprietary epothilone D class with properties of other epothilones to produce an active, well-tolerated and easily formulated anticancer agent," said Robert G. Johnson, Jr., M.D., Ph.D., Kosan's President and Chief Executive Officer. "With the ongoing support from our partner Roche, we can continue our broad- based clinical program for the development of improved epothilones such as KOS-1584, which we believe ultimately has the potential to compete successfully in the large taxane market."
Kosan and Roche established a global development and commercialization agreement for epothilones to treat cancer in September 2002. Under the terms of the agreement, Roche will fund development activities and have the worldwide exclusive rights to market and sell R1645 if approved. Kosan will co-develop and have the right to co-promote the product in the U.S. Kosan is eligible to receive additional payments upon achievement of certain clinical, regulatory and commercial milestones. Kosan will receive royalties on sales and may further increase such royalties through a buy-in option at a later stage of clinical development.
About R1645 (KOS-1584)
Kosan has reported data from two Phase 1 clinical trials of KOS-1584 using different dosing regimens. In both of these trials, R1645 demonstrated meaningful antitumor activity and a high level of tolerability. Both of these trials are ongoing with the goal of identifying the recommended Phase 2 dose and regimen.
In a Phase 1 open-label clinical trial of R1645 being administered as a single agent on a weekly dosing schedule, antitumor activity was observed in 17% of 37 patients with advanced solid tumors who had been heavily pre-treated (median of five prior chemotherapy regimens). One confirmed partial response (44% tumor shrinkage by RECIST) was observed in a patient with non-small cell lung cancer. One patient with advanced refractory ovarian cancer had a 40% decrease in CA125 tumor marker, and four patients experienced stable disease over four or more cycles of treatment (greater than or equal to 16 weeks). Common toxicities were generally low-grade and typical of a cytotoxic agent and were most frequently gastrointestinal.
In an open-label Phase 1 trial of R1645 being administered as a three-hour intravenous infusion every three weeks, conducted in 45 patients with advanced solid tumors, antitumor activity was seen in 29.5% of patients. One patient with ovarian cancer (six prior therapies) had an unconfirmed partial response (31% tumor shrinkage by RECIST) with 62% decline in CA125 after the second cycle. Twelve patients experienced stable disease after four or more cycles, including one patient with ovarian cancer who had a 28% decrease in CA125 after six cycles of treatment. In this trial, R1645 was well tolerated. Common toxicities were primarily gastrointestinal (grade 1 and 2) and fatigue.
About Epothilones
Epothilones are anticancer agents which inhibit cell division with a mechanism of action similar to taxanes, one of the most widely used classes of chemotherapeutic agents. Epothilones have demonstrated activity in taxane- sensitive and taxane-resistant tumors. Kosan's epothilones are designed to be superior to other epothilones, having the potential to overcome multi-drug resistance, to be synergistic in combination with other therapies and have a broad therapeutic index against a wide range of tumors. |
