Pioneering immunotherapy company faces greater competition in treating prostate cancer.

Back in 2010, Seattle-based Dendreon Corporation hit a medical milestone when its autologous vaccine for castration-resistant prostate cancer, Provenge (sipuleucel-T), became the first oncology immunotherapy approved by the U.S. Food and Drug Administration (FDA). Since then, the company has struggled with its business milestones. In recent months, Provenge sales have stalled, and in July Dendreon announced it would lay off 600 staff and close one of its facilities for producing the vaccine.

The company's misfortunes reflect heavy competition in prostate cancer treatment more than declining confidence in autologous vaccines for cancer, says Katherine Xu, PhD, an equity research analyst with William Blair & Co., in New York, NY. “If Provenge had been approved 10 years ago it would have had a much better launch,” she says. “We've got newer oral medications now with better survival data and better pricing.”

Prepared by incubating a patient's dendritic cells with an immune stimulator—granulocyte macrophage colony-stimulating factor—Provenge was associated with a 4.1-month mean improvement in overall survival, from 21.7 to 25.8 months, during the IMPACT phase III clinical trial. A course of 3 intravenous treatments costs $93,000—all of it paid upfront to Dendreon, which prepares the vaccine at a centralized facility.

By contrast, Zytiga (abiraterone; Johnson & Johnson), an oral drug approved by the FDA in April 2011 for the same patient population, costs $6,000 per month. Another oral drug for late-stage prostate cancer, enzalutamide (formerly MDV3100; Medivation), is expected to win FDA approval later this year.

Another issue is that Provenge doesn't easily lend itself to measurable benefits for individual patients: it has virtually no effect on prostate-specific antigen levels, nor does it reduce tumor size. In fact, tumors typically grow larger because of T-cell infiltration during treatment. Without measurable indicators, patients and doctors can only take it on faith that the drug is working.

Moreover, patients must endure 3 rounds of apheresis to supply the requisite cells, points out James Gulley, MD, PhD, deputy chief in tumor immunology at the National Cancer Institute. “If off-the-shelf vaccines are shown to be as effective as autologous vaccines, then logistics favor the simpler, more expedient, and less costly approach,” he says.

Xu adds, however, that despite the challenges associated with autologous vaccines, they can succeed in the marketplace with the right disease and the right staging. “This isn't necessarily a commercial failure that can be extrapolated to other autologous treatments,” she says.