By Randall Osborne

Bolstered by its $10 million private placement earlier this year, Onyx Pharmaceuticals Inc. started a third Phase II trial of its lead cancer therapeutic, ONYX-015, in head and neck cancer patients.

"This is the right way to use Phase II studies, in an efficacy and dose-seeking fashion, and not take the first data and rush into a pivotal trial," said Hollings Renton, president and CEO of Richmond, Calif.-based Onyx.

ONYX-015 is a genetically engineered adenovirus that has been shown to replicate in and kill tumor cells deficient in p53 tumor-suppressor gene activity. A mutation in p53 is the most common type of genetic abnormality in cancer, occurring in more than 50 percent of human tumors.

The first Phase II trial, a single-agent study with multi-day administration, began last July. Twenty-five patients have been treated, and data will be released this spring.

The second trial, begun in October, combines ONYX-015 with two chemotherapeutic drugs.

"We've had some interesting additive effects with chemotherapy, and we don't think there are any overlapping toxicities," Renton told BioWorld Today. Some data may be available from that trial also in the spring.

In the new trial, up to 30 patients will be treated daily with ONYX-015 alone for five days during two consecutive weeks.

"It's the high-dose arm of the single-agent study," Renton said.

After a third week, with no treatment, patients will be evaluated and may continue for another cycle or get maintenance treatment.

ONYX-015 represents "a very active platform for us," Renton said. A Phase I trial has been completed of the drug in colorectal cancer that has metastasized to the liver.

"We're preparing to move into a Phase II study using hepatic-artery infusion," he said, rather than administering the drug directly into the tumor.

The broad strategy for liver cancer (unlike head and neck) is to develop direct, then regional and finally systemic treatments, Renton added. "We need more experience with regional routes," which the hepatic-artery infusion is expected to provide, he said.

Delivery may ultimately be done intravenously or through another formulation, such as polyethylene glycol. "But that's really a second-generation product," he said.

Another Phase I study is under way in pancreatic cancer.

"In the pancreas, we'll be moving into endoscopic ultrasound delivery," Renton said.

A third Phase I study is "halfway complete" in ovarian cancer, delivering the drug by way of an indwelling catheter.

In January, Onyx raised $10 million in a private placement and expanded its collaboration with the Parke-Davis division of Warner-Lambert Co., of Morris Plains, N.J. to a potential value of $50 million in funding and milestones over a six years. (See BioWorld Today, Jan. 16, 1998, p. 1.)

Onyx's stock (NASDAQ:ONXX) closed Friday at $7.187, down $0.187. *

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