West Coast Editor

Lorus Therapeutics Inc. said its Phase III study with Virulizin against pancreatic cancer missed its primary endpoint but yielded what the company called "promising trends" in top-line data.

Wall Street proved unforgiving and whacked the company's stock (AMEX:LRP) by more than 52 percent to close Tuesday at 36 cents, down 40 cents.

"I think the [trial] results could be called mixed,'" said Jim Wright, CEO of Lorus, during a conference call with investors. "We're right in the middle of looking at data - in fact, we don't have all the data yet - but we're very keen about the subgroups analysis that's gone on. We feel we've identified patients that benefit from the use of Virulizin."

Lorus, he added, was "in a lot of detailed discussion with many partner possibilities," as would-be collaborators waited for the first look at Virulizin data. "I don't see any reason to doubt they [would] still want to talk to us about this." Full results are expected in the next six weeks to eight weeks.

The Lorus trial compared the macrophage stimulator Virulizin plus gemcitabine (sold as Gemzar by Indianapolis-based Eli Lilly and Co.) to placebo plus gemcitabine in chemotherapy-na ve patients with locally advanced or metastatic prostate cancer. For the efficacy-evaluable population, data showed that adding Virulizin to gemcitabine reaped a median overall survival of 6.8 months and a one-year survival rate of 27.2 percent, compared to six months and 16.8 percent for placebo plus gemcitabine.

In the intent-to-treat population, the median overall survivals were 6.3 months for Virulizin plus gemcitabine, with a one-year survival rate of 25.9 percent, compared to six months for placebo plus gemcitabine, with a one-year survival rate of 17.6 percent.

Comparisons of the overall survival times fell short of statistical significance, but Lorus pointed to three subsets that hold hope. Among them were patients on Virulizin-plus-gemcitabine treatment with ECOG performance status of 0 or 1 - those made up 68 percent of the evaluable population. They showed a median overall survival of 8.2 months compared to 6.3 months for ECOG 0/1 patients given placebo plus gemcitabine (p=0.063), a result that neared statistical significance.

The ECOG performance scale is named after the Eastern Cooperative Oncology Group, a clinical research organization (funded mainly by the National Cancer Institute) that established the measuring system. Also noted in the trial's ECOG 0/1 population were one-year survival rates in the evaluable population of 32.2 percent in the Virulizin plus gemcitabine patients compared to 20.1 percent in the gemcitabine plus placebo treatment arm.

Checking patients with metastatic (as distinguished from locally advanced) pancreatic cancer - 73 percent of the evaluable population - researchers found those on Virulizin plus gemcitabine showed a positive trend in median overall survival of 6.1 months compared to five months with placebo plus gemcitabine. One-year survival rates in that population were 24 percent in the first category compared to 11 percent in the other.

The trial allowed for an optional second-line therapy stage, whereby patients could continue to receive the study drug or best supportive care after disease progression. Median overall survival in the intent to treat and efficacy evaluable populations were eight and 8.2 months, respectively, for the Virulizin-plus-gemcitabine group, compared to seven months for both the intent-to-treat (p=0.066) and the efficacy-evaluable (p=0.068) population control groups. There again, statistical analysis showed a "trend to significance," favoring continued Virulizin over placebo.

Virulizin proved well tolerated with no major differences observed between the drug-plus-gemcitabine arm and the control group.

Bruce Silver, the contract research organization medical and safety monitor for the trial over the past three years, said he was "reluctant" to make comparisons of the Virulizin study with trials testing Tarceva (erlotinib).

Last month, the FDA's Oncologic Drugs Advisory Committee voted 10-3 to recommend approval of the tyrosine kinase inhibitor of EGFR, for which Melville, N.Y.-based OSI Pharmaceuticals Inc. submitted a supplemental new drug application. The company seeks clearance for 100 mg of Tarceva plus gemcitabine as a first-line treatment in patients with locally advanced, unresectable or metastatic pancreatic cancer. (See BioWorld Today, Sept. 14, 2005.)