Staff Writer

Cancer vaccine companies are no longer Wall Street's red-headed stepchildren, forced to hide their true nature behind deceptively alluring phrases like "specific active immunotherapy." In fact, publicly traded companies with late-stage cancer vaccines have nearly doubled their worth over the past two months, their stocks climbing an average of 92 percent. Some have soared even higher: Antigenics Inc. is up about 300 percent since mid-April, while Dendreon Corp. has gained 235 percent.

On the private side, Pique Therapeutics Inc. just closed an oversubscribed Series A round for cancer vaccines. And in other cancer vaccine news: Merck KGaA started a Phase III breast cancer trial with Stimuvax, Merck & Co. Inc. advanced a Phase I cancer vaccine trial, Apthera Inc. licensed NeuVax South Korean rights to Kwang Dong Pharmaceutical Co. Ltd., Lytix Biopharma AS and KAEL-GemVax teamed up on a cancer vaccine program, and Pro-Cure Therapeutics Ltd. signed a deal with Adjuvantix Ltd. to develop a prostate cancer vaccine - all in the last two months.

After years of skepticism thanks to late-stage failures by the likes of Cell Genesys Inc., Favrille Inc., Genitope Corp., CancerVax Corp., Progenics Pharmaceuticals Inc. and many others, sentiment has swung the other direction, and a cancer vaccine craze is upon us, said Joseph Pantginis, an analyst with Merriman Curhan Ford and Co.

It's all due to Dendreon, which in April announced that prostate cancer vaccine Provenge (sipuleucel-T) significantly improved survival in a confirmatory Phase III trial. It was the first definitively positive Phase III data with a cancer vaccine, proving the approach can potentially work and paving the way to FDA approval. (See BioWorld Today, April 29, 2009.)

But while many cancer vaccine companies are basking in Dendreon's reflected glow, few appear quite ready to follow in its footsteps.

Antigenics owes most of its impressive stock performance of late to data presented at the American Society of Clinical Oncology (ASCO) meeting showing that kidney cancer vaccine Oncophage (vitespen) reduced the risk of death by 46 percent (p = 0.036) in a Phase III trial follow-up. But the Phase III study missed its primary endpoint of improving progression-free survival and secondary endpoint of improving overall survival - the good data came from a subset analysis. Oncophage is approved in Russia and under review in Europe. Antigenics isn't taking its chances with the FDA yet.

Biovest International Inc. has seen a 62 percent stock gain since mid-April also mostly due to ASCO data. The company's BiovaxID, a personalized anti-idiotype vaccine, induced median progression-free survival of 44.2 months compared to 30.6 months for control (p = 0.045) in a Phase III non-Hodgkin's lymphoma study. But again, the data came from a subset. Biovest's parent company Accentia Biopharmaceuticals Inc. filed for bankruptcy protection.

Other Phase III cancer vaccines include Merck KGaA and Oncothyreon Inc.'s Stimuvax, now in Phase III trials for both lung and breast cancer based on a Phase II lung cancer trial that failed but showed strong survival in a retrospective subset analysis. And there's AVAX Technologies Inc.'s M-Vax for melanoma, which has been in Phase III since 1998, plagued by manufacturing problems. And Oxford BioMedica plc's TroVax for kidney cancer, which was dropped by partner Sanofi-Aventis SA after a Phase III trial was halted.

None of this is to say Dendreon's road to positive Phase III data was smooth; the company had its fair share of subset data, retrospective analyses and protocol changes. In the end, the FDA made the company run a confirmatory pivotal trial, which ultimately proved Provenge's survival benefit.

But even the best-laid confirmatory plans don't always work, as Synta Pharmaceuticals Corp. and GlaxoSmithKline plc know all too well after watching melanoma drug elesclomol fail a confirmatory Phase III study despite solid Phase IIb data. (See BioWorld Today, March 2, 2009.)

Whether Dendreon's path will serve as a model for others in the field or just an example of extraordinary good luck remains to be seen. In the interim, cancer vaccine stocks remain cheap despite their recent run-up, and many investors believe their limited downside and potentially significant upside make them worth the gamble.