BioWorld International Correspondent

LONDON - Shares in Xenova Group plc fell by 14.5 pence to 23.5 pence Friday when partner QLT Inc. announced patient enrollment in two Phase III studies of tariquidar was suspended because of safety concerns. The shares continued to fall on Monday morning, losing a further 2.5 pence to 21 pence.

The trials of tariquidar in combination with the standard chemotherapy regimens of paclitaxel plus carboplatin, or vinorelbine alone, will be held up for approximately three months pending an interim safety and efficacy analysis. That will be carried out by the independent data and safety monitoring committee (DSMC) that is overseeing the trials.

Paul Hastings, president and CEO of Vancouver, British Columbia-based QLT, told a teleconference audience the temporary halt to enrollment was disappointing but he was encouraged that existing patients will continue to be treated. Hasting said this was "a good signal there could be enough benefit [from taking tariquidar] to offset increased toxicity."

Hastings said the DSMC "had not come to its decision easily," and had stated all data should remain blinded in order to preserve the integrity of the trial. The DSMC said that its recommendations "provided the best opportunity for these trials to remain intact and to serve, in their entirety, as pivotal registration trials for regulatory purposes."

Hastings stressed that the committee has not seen any efficacy data, adding, "You must not draw any conclusions about the future of tariquidar until the interim analysis is completed." Between now and the completion of the interim analysis QLT will prepare for the continuation of the trial.

The two trials have already enrolled about one-third of the total population of 1,000 patients (500 in each trial). The first 150 of them will now be assessed and monitored for three months, while the rest continue to receive treatment. Hastings said the 150 patients should be sufficient to see differences in response rates, allowing an initial assessment of efficacy vs. safety. Efficacy will be assessed by using CAT scans to measure tumor shrinkage.

The trials are designed to show that tariquidar enhances the efficacy of chemotherapy by preventing tumors developing resistance to the treatment. It does so by inhibiting expression of P-glycoprotein, a membrane protein that pumps chemotherapeutic agents out of cancer cells.

Mohammad Azab, QLT's chief medical officer, said the company has been reviewing overall adverse events in the trial each day, without knowing which patients are receiving which treatment. "What we are seeing is what you usually see with cytotoxics. We are not seeing anything you would not expect," he said.

The guidelines in the trial protocol say that efficacy in the tariquidar arm should be higher than in the placebo arm. Azab said this needed to be viewed in context. "Most regimens that have increased efficacy have increased toxicity in some respect. Increased toxicity could be acceptable if there was increased efficacy."

There was minimal interaction between tariquidar and cytotoxic agents in Phase II, but there was no control arm in those trials.

QLT is continuing its open-label Phase II trial of tariquidar in breast cancer.

Xenova signed the deal with QLT in August 2001, giving QLT development and licensing rights in North America and Mexico. Slough-based Xenova retains the rights in Europe and elsewhere, and on Monday said it intends to establish further collaborations. Commenting on the interruption, CEO David Oxlade said, "Although enrollment has been temporarily suspended for tariquidar, the trials continue and both we and our partner QLT remain confident in the long-term potential of the drug."