BioWorld International Correspondent

LONDON - Onyvax Ltd. is discussing the design for a Phase III trial of its prostate cancer vaccine with regulators, following the publication of final Phase II data showing a significant extension of progression-free survival in patients with advanced disease.

Manufacture of vaccine for the trial has begun, and with the number of subjects in Phase III expected to range from 330 to 660 patients, the London-based company now is weighing its options on how to finance the trial.

"The field [of cancer vaccines] has moved beyond clinical proof of principle, and more into the practicalities of manufacturing and registration," Anthony Walker, CEO, told BioWorld International.

In 26 men with advanced hormone-resistant prostate cancer, with no bone metastases, the median progression-free survival was 58 weeks, compared to an expected 26 to 29 weeks. Patients showed biochemical and immunological responses to the Onyvax-P vaccine, which consists of three inactivated cell lines derived from tumors at different stages of development. The mixture is active against a range of prostate cancer-associated antigens.

Eleven patients experienced a prolonged, statistically significant reduction in the rate of increase of prostate-specific antigen (PSA), a blood marker for prostate cancer, which has levels that generally increase exponentially at that stage of the disease.

"In these 11, PSA velocity was increasing [on average] half as fast as it was before the vaccine was given," Walker said.

Vaccinated patients who showed a clinical slowdown in disease exhibited evidence of an immune response, including proliferation of T cells and a cytokine response. Overall, the treatment was well tolerated.

Results from a second cohort in the study of 20 patients with bone metastases will be published later this year.

Onyvax was founded in 1997 and raised £4.3 million (US$7.9 million) in its first funding round in December 1997, and £11.6 million in November 2000. Walker said the company has cash to last until the second half of 2005.

"We have enough to pay for the manufacturing [of Onyvax-P] for the [Phase III] trial, and we are working on the usual approaches to raise money for the trial itself. How much we need to raise will depend on the final design of the trial."

Although not ruling out finding an industrial partner to pay for Phase III work, Walker said Onyvax would like to keep control of the product.

Onyvax has backed off development of its colorectal cancer vaccine. That is in a physician-initiated Phase II trial, but it has proved an expensive indication in which to develop.

"For best effectiveness you need patients with a low burden of disease, because a high tumor burden is immunosuppressive," Walker said. As a result, there is a long follow-up period, and although the cancer is a good target for a vaccine, "we can't afford a long-term trial," he added.

A third vaccine, Onyvax-O, for ovarian cancer, being developed in collaboration with the Mayo Clinic, of Rochester, Minn., is due to enter Phase II trials by the end of 2005. Other vaccines against myeloma and bladder cancer are in preclinical development.

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