National Editor

With results in hand from a pivotal Phase II/III trial testing its anticancer drug, Onco TCS, in aggressive non-Hodgkin's lymphoma, Inex Pharmaceuticals Corp. was confident the data will hold up in a new drug application to be filed in the third quarter of 2003.

Investors apparently were not so confident. The Vancouver, British Colombia-based company's stock (TSE:IEX) fell C$2.65 Tuesday, or 33.1 percent, to close at C$5.35 (US$3.44).

"The company kind of got caught between a rock and a hard place," said Brian Bapty, analyst with Raymond James Ltd. in Vancouver, who said Wall Street will need some time to sort out the data - which are only the "tip of the iceberg" anyway.

Patients evaluated in the trial were "pretty desperate," Bapty told BioWorld Today, noting that, on average, they had failed four previous regimens. Overall response rate was 24 percent, as compared to a previous Phase I/II trial that garnered a 44 percent response rate.

"That's a little tough," Bapty said. "But in the patient pool that you would have expected to look more like the last study, they had a 50 percent response rate." Neither Bapty nor his firm owns Inex stock.

"There was a real negative in that [Inex] pushed their time filing for the NDA out from the first quarter to the third quarter of 2003," he added. "That is a delay, and that's a material change," although probably not enough to explain entirely the hit taken by the stock, he said.

David Main, Inex's president and CEO, said not everyone grasped the data's importance immediately.

"Sometimes the market wants everything black and white," he said.

In the study of 102 patients, the overall response rate to Onco TCS - Inex's liposomal version of the widely used agent vincristine - was 24 percent, including five patients whose tumors were completely eliminated and 19 patients whose tumor volume was reduced by more than 50 percent.

The median duration of response for the 24 responding patients was about three months, and another 24 percent of patients had their disease stabilized. Even though the patients had been through an average of four treatment regimens, 75 percent had disease still classified as resistant to their last round.

"Fifty percent of the patients were completely refractory to their last therapy," Main told BioWorld Today.

"They're end-stage patients, so you're not expecting to cure them, but hoping to control the cancer for as long as possible," he added. "There's no good precedent on what to expect. On every relapse, the response rate goes down and so does the duration of response."

Bapty said that, given that the trial patients' previous treatments "likely included vincristine," the results are worthy of respect.

"You've got a population destined for palliative care, and you got a response," he said. "Is this a good rate, given what's available? Well, there's always something available. You can always throw some mishmash of chemotherapy at [the disease] and get some kind of response. But as a single-agent, this is fairly impressive, and it's not a bad safety profile."

Five patients' tumors were eliminated completely.

"It's a small number but it's surprising," Main said. "We didn't expect to see any."

Inex said it expects to have a review by the FDA's Oncologic Drugs Advisory Committee (ODAC) and a response from the FDA within six months of filing, with a planned launch in the second half of 2004, if all goes well.

Main acknowledged that ODAC is "always a very public forum and very politically charged, but in the end it's people who are experts in clinical medicine" - like those on the advisory panel assembled by Inex that gave its positive opinion of the data Monday.

Inex Pharmaceuticals Corp. presented interim results from an ongoing non-Hodgkin's lymphoma Phase II trial at the American Society of Clinical Oncology meeting in Orlando, Fla., and the results showed all patients responded to the treatment.

In May, Inex offered interim results from a Phase II trial with Onco TCS in combination therapy - as opposed to single agent in the pivotal trial - for first-line treatment of aggressive NHL, and results from 26 patients in the Phase II trial showed all patients responded to treatment. (See BioWorld Today, May 22, 2002.)

The two trials provide an understanding of Onco TCS's efficacy at "both ends of the spectrum," Main said, adding that complete data will be offered at the American Society of Hematology meeting, which takes place later this month in Philadelphia.