The pancreatic cancer community received another blow on Wednesday when Therion Biologics Corp. announced that Panvac-VF failed to meet its primary endpoint of improving overall survival compared with palliative chemotherapy.
The news came one day after South San Francisco-based Genentech Inc. delivered data showing Avastin (bevacizumab), when used in combination with gemcitabine chemotherapy as a first-line treatment, also missed its primary endpoint of overall survival. Panvac-VF was being evaluated as a second-line treatment.
When Cambridge, Mass.-based Therion submitted its application to the FDA to conduct a Phase III trial under a special protocol assessment, the company prepared published data of 12 different randomized pancreatic cancer trials.
"Median survival of that group was three months, no matter what the agent used was," said Mark Leuchtenberger, president and CEO of Therion. "Unfortunately, I think what we've done is just confirm those data right now."
The Phase III trial, begun in May 2004, enrolled 255 patients with advanced pancreatic cancer and was aiming to show a 50 percent improvement - about a two-month extension - in survival over control chemotherapy. The study was designed from two Phase I studies that showed a median overall survival of more than six months.
"This is a big substantial disappointment," Leuchtenberger told BioWorld Today, "but I think the evidence for vaccine therapy or active immunotherapy exists in our other trials."
Panvac-VF is designed to stimulate the immune system to target and destroy cancer cells expressing carcinoembryonic antigen and mucin-1, which are found on more than 90 percent of pancreatic tumor cells. The vaccine incorporates Therion's triad of co-stimulatory molecules (B7.1, ICAM-1 and LFA-3) to enhance and sustain a targeted immune response. The product is being evaluated in several studies sponsored by the National Cancer Institute to treat advanced breast, ovarian, colorectal and non-small-cell lung cancers.
Leuchtenberger said it is unlikely that Panvac-VF will be further developed as a second-line treatment for pancreatic cancer, although the company is just starting to "look below the top-line" data. The company had been expecting to file a biologics license application before the end of the second quarter.
While Panvac-VF received the "green light" at its interim analysis, Leuchtenberger said, Avastin was stopped early after an interim analysis indicated the unlikelihood of success. Genentech's trial included 602 patients. (See BioWorld Today, June 28, 2006.)
Nearly 34,000 Americans will be diagnosed this year with pancreatic cancer, and 32,300 will die of the disease, according to the American Cancer Society. Front-line therapy consists of surgery, radiation and chemotherapy with gemcitabine. When that fails, patients are treated with other single-agent chemotherapies to address symptoms, but there is no second-line pancreatic cancer therapy approved in the U.S.
"It's just a notoriously hard-to-treat disease that has gotten even harder," Leuchtenberger said.
Therion previously announced plans by its lead investor, Hans-Werner Hector, a founder of the enterprise software company SAP AG, of Walldorf, Germany, to sell the company as a way of getting an exit without a public financing. The sale was expected to come soon after the Phase III data of Panvac-VF, and the Phase II data of Prostvac-VF, were announced - regardless of whether the therapies hit their endpoints.
Therion said Wednesday that its investors have identified an investment bank to manage the sale, which should conclude within the next several months.
"Our objective now is to make sure the technology finds a good home," Leuchtenberger said.
Therion secured a $50 million line of credit from lead investor Hector last December, giving it enough money to take it into 2007. Since its 1991 inception, the company has raised more than $160 million. (See BioWorld Today, Dec. 28, 2005.)
The value of the company may have been hurt by the failed Panvac-VF trial, but also by a Phase II study of Therion's second product, Prostvac-VF, which also missed its primary efficacy endpoint, the improvement of progression-free survival in advanced prostate cancer patients. Data from the randomized, double-blind, placebo-controlled trial that evaluated the product in men with advanced prostate cancer were presented at the American Society of Clinical Oncology Annual Meeting in Atlanta earlier this month.
Preliminary results did show, however, that Prostvac-VF was associated with a potential reduction in mortality compared to placebo. As a result, Therion has formalized plans with the Eastern Cooperative Oncology Group to move the product into a Phase III trial.