BioWorld Today Correspondent

LONDON - Oxford BioMedica plc's share price plunged 60.3 percent to 7.35 pence (US15 cents) on Friday when the company said the Phase III trial of its cancer vaccine TroVax would not reach its primary endpoint of overall survival in renal cancer.

As a result, the product, which was partnered with Sanofi-Aventis SA in a $690 million deal agreed to in March 2007, will not meet the terms of the FDA's special protocol assessment, and a further trial will be required to register TroVax in that indication.

The news follows the fourth interim review by the data safety monitoring board, carried out at the point when 190 of the patients recruited into the 733 patient study had died. While the primary endpoint will not be reached, the board recommended the trial continue in a blinded form until its end, but that no further vaccinations should be administered.

The study protocol allowed for patients to receive up to 13 vaccinations, and the implication is that after a certain number of treatments the vaccine becomes less effective. Mike McDonald, Oxford BioMedica's CEO, said the data to which the company has access "suggests there may be an optimal number of doses and perhaps going beyond that in frailer patients may be unhelpful."

The intention is to amend the statistical plan of the study to determine whether patient outcome is dependent on the number of doses administered. McDonald said there has been a high degree of retention and more than 500 patients remain in the trial. All patients have received at least four vaccinations, and above that, the average number of doses received is eight. McDonald said it will be possible to assess the dose effect, and running the study to completion will provide "strong data to support or refute the hypothesis that there could be overtreatment."

The TroVax Renal Immunotherapy Survival Trial (TRIST), a randomized, placebo-controlled study was initiated in November 2006 and recruitment of 733 patients at more than 100 sites was completed in March.

While TRIST will not deliver data that can be used for registration, McDonald said he is optimistic that TroVax may yet show benefits. "This is clearly disappointing. However, there is good reason to continue the study, and potentially a late survival benefit for TroVax may still be demonstrated."

The fact that TRIST will not meet its primary endpoint has implications for two Phase III trials in colorectal cancer that Sanofi-Aventis was planning to start later this year. McDonald said it was too early to say whether and when the trials, in which it was planned to recruit 4,300 patients, would go ahead.

"There will be valuable information from [the TRIST] study. It is premature to draw any conclusions, including whether [Sanofi-Aventis] will have to wait until the end of the [TRIST] trial to derive information from it," McDonald noted. He said he still expects TRIST to report as planned in the first quarter of 2009.

Although the financial fallout for Oxford, UK-based Oxford BioMedica is not clear at this stage, the fact that TRIST will not provide the data to support a regulatory submission and that the colorectal cancer trials are likely to be delayed, will mean milestone payments from Sanofi-Aventis will not be triggered as expected.

Andrew Wood, Oxford BioMedica CFO, told an analysts' meeting that even if no milestones are received the company's cash position of £30 million (US$59.7 million) is sufficient to last until the end of 2009. "But we are now looking at our assets to see how to generate the best value for shareholders and patients, given that milestones will, at best, be delayed," he added.

An additional Phase II trial of TroVax, which uses Modified Vaccinia Ankara to deliver the gene for 5T4 - a tumor antigen found on many solid tumors - is in progress in prostate cancer.

In more than 900 patients treated with TroVax to date, the majority have mounted an immune response, with the strongest responders showing the greatest clinical benefit. There have been no safety issues.