Assistant Managing Editor

Last year's decision to amend its Phase III protocol to include subset analyses could end up reviving excitement in Oxford BioMedica plc's troubled cancer vaccine, as data presented at this week's European oncology conference in Berlin showed that TroVax had significant activity in one predefined patient group in the Phase III renal cancer trial.

Data from the 733-patient TRIST (TroVax Renal Immunotherapy Survival Trial) study showed no significant survival advantage in the treated group over placebo for the total population, with median survival of 20.1 months for patients on TroVax vs. 19.2 months for placebo.

Those results weren't unexpected given the fact that a data monitoring board concluded in July 2008 that the study would not reach its primary overall survival endpoint, though some investors might have been reacting to that old news Tuesday, sending shares of the Oxford, UK-based firm (LSE:OXB) falling to 11.25 pence (US18 cents), down 1 pence. (See BioWorld Today, July 14, 2008.)

After being hit with the monitoring board's recommendation last year, the company went to the FDA with proposed revisions to its special protocol assessment for TRIST that would allow for subset analyses. (See BioWorld Today, Oct. 8, 2008.)

The new data from Oxford BioMedica's trial came from those analyses and showed that one group of patients, specifically those with good prognostic profiles receiving interleukin-2 as their standard of care, had reduced risk of death by 46 percent in the TroVax arm over placebo, with a hazard ration of 0.54 and a "p" value of 0.046.

Also encouraging is that median survival for that TroVax subset had not been reached as of interim data collection. Median survival for the placebo group was 19.6 months.

But the real question is whether those results will be enough to attract a new partner to fund a confirmatory Phase III study of the 5T4 antigen-targeting vaccine.

Oxford BioMedica said in July that the FDA has provided a path forward for TroVax development in several cancer settings, but the firm has said it has no intentions of funding another Phase III program on its own.

Former TroVax partner, Paris-based Sanofi-Aventis Group, bailed out of the deal earlier this year, citing a reorganization of its pipeline that prompted it to drop TroVax among 13 other programs. But Oxford BioMedica managed to score an £11 million termination fee, and at the same time, it added another £18 million in a new, early stage Sanofi deal using its LentiVector technology to develop gene-based therapies for eye diseases. (See BioWorld Today, April 30, 2009.)

With enough cash on hand to support operations into 2012 and, finally, some promising TroVax data in hand, Oxford BioMedica expects to move into partnering talks, reaching out to companies and the oncology community "as soon as possible," CEO John Dawson stated in a press release.

The TRIST trial was designed to test TroVax in patients with advanced or metastatic renal cancer, who had either a good or intermediate prognosis and were randomized to receive either IL-2, interferon-alpha or Sutent (sunitinib, Pfizer Inc.) as standard of care. Additional data showed that patients with normal vs. abnormal baseline platelets had a more favorable immune response to TroVax, as did patients with lower baseline platelet and monocyte levels and higher hemoglobin levels, who showed a 27 percent reduction in the risk of death on TroVax over placebo.

TroVax was well tolerated, with the most common treatment-related adverse events being pyrexia, fatigue, weight loss and nausea.

In other conference news:

• Algeta ASA, of Oslo, Norway, reported clinical data from Phase II trials of Alpharadin, an alpha-emitting pharmaceutical recently partnered in a potential $800 million deal with Leverkusen, Germany-based Bayer Schering Pharma AG. Among results presented included two-year follow-up data from the 64-patient BC1-02 study, showing that 10 of 33 (30 percent) patients with hormone-refractory prostate cancer with bone metastases receiving Alpharadin were alive at 24 months vs. four of 31 (13 percent) placebo patients. Algeta also showed final results from its 100-patient BC1-03 study, which demonstrated that a single dose of Alpharadin alleviated pain in a dose-dependent manner in HRPC patients and also showed a dose-dependent reduction in bone alkaline phosphatase, a severity marker of bone metastatic disease. And data from a 122-patient BC1-04 study showed that Alpharadin produced a significant prostate-specific antigen response rate.

• Bavarian Nordic A/S, of Kvistgaard, Denmark, presented data from a 125-patient Phase II trial of therapeutic vaccine Prostvac in metastatic prostate cancer, showing that patients in the treatment group had a significantly longer median overall survival (by 8.5 months) compared to the control group. Prostvac also demonstrated a favorable safety and tolerability profile.

• Bayer Schering Pharma AG, of Leverkusen, Germany, presented results from a Phase II trial of oral, multikinase inhibitor regorafenib (BAY 73-4506), showing a 31 percent partial response rate and a 50 percent stabilization rate in patients with metastatic renal-cell carcinoma. Data also showed an estimated median progression-free survival of 8.3 months at the end of the study. At the time of data analysis, 25 patients remained on treatment and 12 of the 15 patients who had achieved a partial response had an ongoing response.

• Genomic Health Inc., of Redwood City, Calif., reported results confirming that the distribution of Oncotype DX recurrence scores in breast cancer patients in Europe and the Middle East is consistent with that observed in the U.S. Oncotype DX is designed to measure the expression of 21 genes of an individual tumor to generate a recurrence score result that quantifies the magnitude of chemotherapy benefit and the likelihood of recurrence for early stage breast cancer patients.

• Helsinn Group, of Lugano, Switzerland, reported data showing that palonesetron, its second-generation 5-HT3 receptor antagonist, improved emesis and nausea control in patients undergoing multiday high-dose chemotherapy and autologous stem cell transplantation. The addition of a second palonesetron dose 48 hours after the first also significantly reduced the detrimental impact of nausea on daily activities. The study accrued 60 patients diagnosed with lymphoma, myeloma, sarcoma, acute leukemia or breast cancer.

• Nektar Therapeutics Inc., of San Carlos, Calif., presented Phase I data showing that NKTR-102, a prodrug of irinotecan, demonstrated efficacy in both of the evaluable patients with recurrent ovarian cancer. Both showed significant antitumor activity, including tumor reductions of up to 37 percent and a decrease in CA-125 marker levels of up to 80 percent. The firm also reported preclinical data, which demonstrated NKTR-102's superiority over irinotecan in an ovarian cancer mouse model at all dose levels, with 100 percent of NKTR-102 animals demonstrating partial or complete tumor regression compared to only of one of 10 animals with a partial response at the highest irinotecan dose. Shares of Nektar (NASDAQ:NKTR) gained 90 cents, or 9.4 percent, to close Tuesday at $10.47.

• Pfizer Inc., of New York, presented longer-term data from its HES (Intergroup Exemestane Study) trial, showing that women who switched to Aromasin (exemestane tablets) after taking tamoxifen for two to three years experienced a significant reduction (18 percent) in the risk of disease-free survival events compared to those who continued on tamoxifen for a full five years of treatment.