By Jim Shrine

Special To BioWorld Today

Onyx Pharmaceuticals Inc. said its viral therapeutic, ONYX-015, in combination with standard chemotherapy produced better and longer responses in head-and-neck cancer patients than chemotherapy alone.

"This is very exciting data," said David Kirn, president of clinical research for Richmond, Calif.-based Onyx. "No one has ever seen anything like this in recurrent head-and-neck cancers. You do not see this response duration and time to progression. We have not seen a single responding tumor progress to date."

Onyx said it will use the Phase II data from 26 patients to support a pivotal study comparing ONYX-015 and the standard regimen of cisplatin and 5-FU against the chemotherapeutics alone. Onyx intends to discuss the trial design with the FDA in the first half of 1999.

Sixteen of the 26 patients in the Phase II study had tumor regression greater than 50 percent, with six of them experiencing complete regressions. The overall response rate was 62 percent and the complete response rate was 23 percent, compared to 35 percent and less than 10 percent, respectively, that would be expected in patients treated with standard chemotherapy.

Typically, the duration of response is about three months in patients using chemotherapy alone. The 16 patients who responded in the trial have been followed for one and a half to 11 months, with a median time to date of more than five months.

"There is almost a doubling of response rate overall and incredible duration," Kirn said. "These tumors are not progressing. We feel this data clearly supports a pivotal trial."

ONYX-015 is an adenovirus that has been genetically engineered so it no longer inactivates the p53 tumor suppressor gene in normal cells. It is designed to replicate in and kill tumor cells deficient in p53 activity. In the Phase II study, the virus was injected directly into tumor sites.

Fifteen of the 26 patients had a single tumor mass and received treatment to their entire cancer. Five of those experienced complete regression. Tumor progression was seen in only one of those 15.

Two of the 15 patients developed a second tumor and were treated at those sites, with both experiencing a complete response in the second site with no additional recurrence.

Search For Phase III Partner Under Way

Kirn, in a conference call Monday, said the results help address the question of redosing. "This is a small number of patients but important anecdotal evidence that we can re-treat patients with this viral therapy," he said.

Hollings Renton, Onyx's president and CEO, said the company anticipates establishing a strategic alliance for ONYX-015 by the middle of next year.

"We feel, to carry out the Phase III trials as efficiently as possible and broaden the market for this agent, that partnering with a major pharmaceutical company is the right approach," Kirn said. "Our plan was to develop this virus through Phase II to prove it was well tolerated and had significant activity which warranted a pivotal trial."

The virus already has been tested in Phase I trials in three other cancer types: pancreatic, liver metastases of colorectal cancer, and ovarian. The Phase II portion of the pancreatic study already has begun, and the others are expected to get under way soon.

ONYX-015 also has been studied as a single agent and produced good responses, Kirn said, but the activity in combination would be expected to be greater than the viral therapy alone. Evidence has shown the agent along with chemotherapy drugs produces regression in both p53 mutants and p53 "wild-type" tumors, he said.

Onyx officials also said they have developed a second viral therapeutic, ONYX-838, that is engineered to replicate in tumor cells and destroy those with defects in the restinoblastoma gene pathway, which are present in most human cancers. It also is designed to leave normal cells unharmed. The company said efficacy has been seen in mouse tumor models.

Results of the Phase II study were presented Saturday in San Diego at the Seventh International Conference on Gene Therapy of Cancer.

Onyx's stock (NASDAQ:ONXX), which was as low as $3.375 in September, closed Monday at $7.25, down $1.375. n