BioWorld International Correspondent

Without burning any additional cash, Pharmexa A/S is adding to its project portfolio a second Phase III clinical trial of its lead therapeutic vaccine candidate, GV1001. TeloVax, an investigator-initiated trial in the UK, plans to recruit 1,100 patients with pancreatic cancer. It follows an earlier Phase III clinical trial on the European mainland, called PrimoVax, which got under way last year. (See BioWorld International, May 3, 2006.)

Each is assessing the survival benefit of GV1001 in pancreatic cancer, but their respective designs differ considerably. PrimoVax, which is recruiting 520 patients, comprises a head-to-head comparison with Gemzar (gemcitabine), the current gold standard treatment, which is marketed by Indianapolis-based Eli Lilly and Co.

"The one thing about that study is it gives you a very clean readout," Gary Middleton, chief investigator on the TeloVax trial, told BioWorld International. However, GV1001 is unlikely to replace chemotherapy, unless it achieves a dramatic improvement, he said.

The TeloVax study has three arms, each of which will recruit 370 patients. Those in one arm will receive chemotherapy, comprising Gemzar and Xeloda (capecitabine), alone. A second group will receive chemotherapy for eight weeks, followed by treatment with GV1001. Those in the third arm will receive chemotherapy and vaccine concurrently.

"We're prospectively evaluating not only the impact of the vaccine per se but also we're asking questions about how best to combine the vaccine with chemotherapy," said Middleton, who is based at the Royal Surrey County Hospital, in Guilford, UK. "It's not a me-too' study. It's a fundamentally different question really."

The comparator arm in the TeloVax study differs from that in the PrimoVax trial because the addition of Xeloda or Tarceva (erlotinib) to Gemzar recently has been shown to provide a small but statistically significant survival benefit in pancreatic cancer, Middleton said. In the case of capecitabine, it's the equivalent of a 7 percent improvement, approximately, in the 12-month survival data.

The design of the other two arms was influenced by research over the past decade, Middleton said, which indicates that chemotherapy actually may enhance rather than undermine the immune response to cancer by increasing antigen presentation and by having an adjuvant or stimulatory effect on the immune system following the induction of apoptosis in cancerous cells.

Pancreatic cancer is a difficult condition to detect and to treat. Only about 10 percent of cancers are operable, Middleton said. Patients with untreated cancers generally survive for three to four months. Treatment with Gemzar can double that figure. "If you look at Gemzar as a monotherapy, it's remarkably consistent, giving you around six months median survival."

GV1001 has shown promise because a group receiving an intermediate dose in an open label Phase I/II clinical trial of three doses of the vaccine achieved median survival of 8.6 months. "The [TeloVax] study is actually powered to detect a 10 percent improvement in 12-month survival," Middleton said.

GV1001 consists of a 16-mer peptide encoding a catalytic domain of the telomerase, an enzyme that is over-expressed in a wide range of cancers. The peptide is processed and presented as both a 16-mer and a 9-mer, Middleton said, and thus elicits both a T-helper cell response and a cytotoxic T lymphocyte response.

Data from the TeloVax trial will not be available until around 2012. "Hopefully the drug will be already registered around that time," Claude Mikkelsen, head of investor relations at Hørsholm, Denmark-based Pharmexa told BioWorld International. PrimoVax is scheduled to finish in 2009, with a filing penciled in for the following year.

Pharmexa also is planning a Phase II clinical trial of GV1001 in liver cancer later this year, the results of which would be available before the year end. The company gained ownership of the vaccine when it acquired Oslo, Norway-based GemVax AS in 2005. (See BioWorld International, April 13, 2005).

Its share price gained about 3 percent on the Copenhagen Stock Exchange following release of the news last Thursday, closing at DKK16.20, up from the previous day's close of DKK15.70.

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