Women were the beneficiaries of the first cancer vaccine―Gardasil, approved in 2006 to prevent cervical cancer. Several weeks ago, the same drug was made available to young males to prevent genital warts. And now it looks as if the first vaccine approved to fight cancer, by enhancing the body's immune response to cancer cells, will benefit males. Last month the Food and Drug Administration committed to deciding the fate of the prostate cancer vaccine Provenge by May 1, 2010. Prostate cancer is an appealing target because it moves slowly (even men whose cancer comes back after prostate surgery often live for well over a decade). That wide window of opportunity gives a vaccine time to prompt the immune system into fighting the body's own cells when they've become cancerous. (The immune system routinely fends off some tumors on its own, generally tiny cancers that are never detected, much less diagnosed.)
But while Provenge is on track to enter the market first, a less-sexy vaccine that hasn't caught the eye of biotech investors could work just as well at a much lower cost.
To the chagrin of patient advocates (and investors), the FDA ruled against allowing Provenge into doctor's hands back in 2007 when the results of its large Phase III trial came in. The trial supported the vaccine's effectiveness—men with advanced prostate cancer lived several months longer after getting the vaccine. But Dendreon, the company that owns the technology, hadn't set out to judge the vaccine's value for extending life. The company had designed the trial, and had so informed the FDA, to assess disease progression—how fast the cancer grew and spread. Those results didn't show that the drug offered a statistically significant improvement. New goal, new game, dictated the FDA. The company had to fund a second large trial, this time designed explicitly to test for survival benefit, if it was ever to see its product enter the U.S. market. The results, announced in April, showed that patients with advanced metastatic prostate cancer who had failed other treatments lived four months longer, on average, if they got the Provenge vaccine. That's statistically significant, but is it clinically significant? Dendreon wants patients and doctors, not the FDA, to decide.
Provenge isn't your typical vaccine. It's custom-made from each patient's dendritic cells. These specialized cells mop up foreign molecules (antigens) and then show them off to the immune system's T-cells. If the T-cells don't like what they see, they seek and destroy any cells that carry the antigen, even the body's own cells. To make the Provenge vaccine, technicians must culture a patient's dendritic cells and expose them to an antigen called PAP, found in cancerous prostate tissue. After the cells take up the antigen, they are reintroduced into the patient's bloodstream in a series of three injections to begin schooling the immune system. Because of all this high-tech labor, Provenge will be very expensive, which has attracted the interest of a lot of investors. A few months more of life for a hefty price is all that most cancer therapies offer, and that won't change with this vaccine.
Now for the cheaper way—David Lubaroff's old-school approach. Lubaroff, director of urology research at the University of Iowa, has fashioned a vaccine from a common cold virus. It can be produced inexpensively in mass quantities like the influenza vaccine. Lubaroff and his team inserted the genetic code for prostate-specific antigen, which is generated by prostate cancer cells, into a weakened virus. When a prostate cancer patient gets Lubaroff's PSA vaccine, the weakened virus causes the body's immune system to think that PSA is a foreign intruder like rest of the virus's proteins, and the T-cells go on a search-and-destroy mission against the invading cancer cells. Lubaroff has already demonstrated this fact in animal models, and this month in the journal Clinical Cancer Research, he reports on the vaccine's first human trial. Only 32 men with advanced prostate cancer got the vaccine—the group was so small because the goal of such a Phase I trial is only to determine whether a drug is safe. That's also why investigators only enrolled men with severe disease who were out of other options. There were no serious side effects. As for cancer fighting, over half of the patients lived longer than would be expected—three patients lived close to four years longer. But the study was too small to say much more.
Men with localized prostate cancer could end up benefiting from a vaccine, but they'd have to get the vaccine only after a prostatectomy to remove the prostate gland. Cancer-fighting vaccines are designed to target your own tissues, and even healthy prostates put out PSA. If you got Lubaroff's vaccine prior to prostatectomy, you'd have a painful inflammation of the prostate gland (prostatitis) as your immune system attacked PSA-producing cells. But while Lubaroff's vaccine and Provenge are being tested in men who have cancer that's spread elsewhere in the body, both vaccines may be more effective if given before that happens. For one thing, men who've received chemotherapy, like some of those in the vaccine trials, may have worn-out immune systems that can't take full advantage of the vaccine's stimulation. For another, it makes sense to nip a cancer in the bud.
If the FDA approves Provenge without specific and strong restrictions, some doctors are sure to use it on patients with localized prostate cancer, and they'll be theoretically correct in doing that. "We thought it would be a harder sell" to do a trial in men with less-advanced disease, says Lubaroff. He thinks cancer vaccines like his would work as effectively, perhaps even more so, in men with cancer that hasn't spread. He has a larger Phase II trial underway, funded by the Department of Defense. For a big Phase III trial like those backing up Provenge, Lubaroff knows he'll need pharmaceutical sponsorship. Will he get such backing? Lubaroff's vaccine is a one-shot, one-size-fits-all deal; there's little opportunity for big money to be made from its manufacture or on the healthcare provider's end. Even the seasonal flu vaccine, which goes out to a far larger "customer base," wouldn't be feasible without special government concessions and sponsorship. But if Provenge goes on the market and doctors offer it to men without advanced disease, the expense will put a huge strain on the healthcare system. If the government truly wants healthcare that is more efficient and affordable, wouldn't it make sense to should seek out and accelerate the development and approval of simple, cheap drugs—like Lubaroff's vaccine?