Staff Writer

Dendreon Corp. made history on Thursday, securing a long sought-after FDA approval for prostate cancer vaccine Provenge (sipuleucel-T).

During a conference call discussing the approval, Dendreon President and CEO Mitchell Gold tossed out phrases like "the dawn of an entirely new era in medicine" and "the Holy Grail of oncology." The hype is absolutely warranted: Provenge is the first therapeutic cancer vaccine to gain FDA approval, and Dendreon fought a long, hard battle to get it there.

Provenge's label is for asymptomatic or minimally symptomatic prostate cancer that has spread to other parts of the body and is resistant to standard hormone treatment. Gold said the inclusion of not just asymptomatic but also minimally symptomatic patients clearly positions Provenge as a front-line treatment and the foundation of a new standard-of-care for metastatic prostate cancer.

Common adverse events called out in the label include chills, fatigue, fever, back pain, nausea, joint ache and headache, while serious adverse events include acute infusion reactions and cerebrovascular events, each of which were observed in 3.5 percent of patients. As part of a post-marketing requirement, Dendreon will further evaluate cerebrovascular events through a registry of 1,500 patients.

As Gold noted in the conference call, Provenge's FDA approval is "just the beginning." Dendreon must now turn its attention to commercialization - no small task considering that Provenge is a personalized vaccine custom-made for each patient. The vaccine consists of autologous antigen-presenting removed from the patient via leukapheresis, co-cultured with a recombinant fusion protein at Dendreon's manufacturing facility, and then delivered back to the patient, with the goal of stimulating a T-cell response against prostatic acid phosphatase (PAP), an antigen expressed in more than 95 percent of prostate cancers.

Dendreon expects to treat the first patient next week. But Chief Operating Officer Hans Bishop acknowledged that demand will exceed supply for the first 12 months. During that time, Dendreon expects to provide Provenge to about 2,000 patients, using product manufactured at its Morris Plains, N.J., plant. The vaccine will be distributed through 50 clinics, all of which participated in the clinical trials.

In early 2011, the N.J.-based plant is expected to come up to full operational capacity, and two additional plants in Atlanta and Orange County, Calif., will come online by mid 2011. When all three plants are up to speed, Gold said Dendreon should be able to support $1.2 billion to $2.5 billion worth of Provenge demand. Some analyst estimates of peak sales exceed $4 billion.

Dendreon's pricing for Provenge came in higher than most analysts had expected, at $93,000 per treatment cycle. One treatment cycle includes three infusions, which are given within about a month. Bishop emphasized that Provenge requires minimal additional costs related to supportive care, unlike many other cancer drugs. He added that, considering Provenge's ability to extend survival by 4.1 months, the drug costs about $23,000 per month of survival, which is similar to chemotherapy drug Taxotere (docetaxel, Sanofi-Aventis Group).

Dendreon anticipates that Medicare and private insurance groups will cover Provenge, but the company also has set up a patient assistance program for those who can't afford the drug.

Provenge is not partnered in the U.S., and while Dendreon previously had been exploring overseas partnering opportunities, the company said it has set those discussions aside and now plans to pursue European approval on its own. Bishop estimated that the European market for Provenge could be twice as big as in the U.S.

While analysts on Dendreon's conference call seemed focused on the hard work that lies ahead, there was no shortage of praise for what Dendreon has already achieved.

The idea of using a vaccine to harness the immune system and fight cancer has captivated scientists since the early 1900s, but putting the theory into practice proved no easy task. Among the biotechs to face failure in late-stage trials are Antigenics Inc., CancerVax Corp., Cell Genesys Inc., Favrille Inc., Genitope Corp., Progenics Pharmaceuticals Inc., Therion Biologics Corp. and many more - including Dendreon itself.

Dendreon's first two Phase III trials of Provenge missed their primary endpoint of time to progression but showed a survival benefit in post-hoc analyses. The company filed for approval, and the FDA's Cellular, Tissue and Gene Therapies Advisory Committee gave Provenge the green light, but the agency itself denied approval until efficacy could be confirmed in another Phase III trial. That trial demonstrated that Provenge reduced the overall risk of death by 22.5 percent compared to placebo (p = 0.032; HR = 0.775) and extended median survival by 4.1 months. (See BioWorld Today, March 30, 2007, May 10, 2007, and April 15, 2009.)

Based on those data, the FDA skipped the advisory panel this time around and approved the drug - earlier, in fact, than its May 1 PDUFA date.

Shares of Seattle-based Dendreon (NASDAQ:DNDN) popped 15 percent, or $5.81, in the few minutes before trading was halted on Thursday. When trading resumed, the stock continued to climb, closing at $50.18, a gain of $10.56, or 26.7 percent, for the day.

And Dendreon's stock had been gaining momentum even before the approval. Since Dendreon first announced positive data from its confirmatory Phase III trial, the stock has climbed more than 1,800 percent from a low of $2.61 in March 2009.