FDA Rejects Promising Prostate Cancer DrugSeptember 2007
By William Faloon
Americans with life-threatening illnesses are denied access to promising therapies, but the federal government does nothing to prohibit high-risk activities that result in people being killed for no worthwhile purpose.
In early December 2006, the number one news topic related to three mountaineers who were lost while attempting to summit Mount Hood in Oregon despite dangerous weather conditions. Huge amounts of public resources were expended in an attempt to rescue the climbers, but to no avail: one was found dead, while the other two are still missing.1
During the very same week in December 2006, about 600 American men with advanced prostate cancer were on the verge of death.2 The federal government prohibited a drug from reaching these prostate cancer victims, even though this drug had demonstrated efficacy in a carefully controlled clinical study. In fact, from the time of the release of the data on this drug in 2002, tens of thousands of American prostate cancer patients have died in the FDA’s waiting room.
The government argues that advanced prostate cancer patients should not risk taking a drug that could cause side effects, even though all these patients face imminent death.
Parachuting to Death off a Bridge
The third Saturday of October in Fayette County, West Virginia is called “Bridge Day.” The highlight of the event involves hundreds of people parachuting off a high bridge. While a handful of minor injuries occur each year, last October’s “Bridge Day” had one person die when his parachute did not open. This is the fourth fatality since this local tradition started.3
There is no talk about banning the bridge jumps, but the federal government holds steadfast that promising drugs cannot be sold to terminally ill cancer patients until the FDA deems them as safe and effective.
No government restrictions on mountain climbing, bridge jumping, or other risky activities that contribute nothing to society, but an armada of federal officers, prosecutors, and FDA investigators are ready to pounce on anyone who dares offer a cancer therapy before it receives official approval.
Drug Shown to Save Lives—But Not Approved!
In mid-2004, I reported in this column about a randomized study involving men with late stage, metastatic prostate cancer who received either an immune-boosting vaccine called Provenge® or a placebo.4 Patients were randomized to receive three vaccinations of Provenge® or placebo over a four-week period. Analysis of the data revealed that the single most important predictor of response to Provenge® was a patient’s Gleason score, a measure of the aggressiveness of a patient’s tumor.5,6
In patients with a Gleason score less than or equal to 7, the placebo group had an average time to cancer progression of 9.0 weeks, compared with 16.0 weeks for the Provenge® group. This finding was statistically significant with a p-value of 0.002 (indicating a two in 1000 probability of this occurring by chance alone). In addition, patients receiving Provenge® whose disease had not progressed six months after randomization had more than an eight-fold advantage in progression-free survival compared with those patients who received placebo (34.7% versus 4%).
However, in the formal protocol of this government-approved study, the primary endpoint was the time to objective disease progression. Comparison of the Provenge®-treated group with the placebo group (using Kaplan-Meier survival curves) revealed a clinical benefit in the Provenge® treated patients (p-value=0.085) that approached but did not achieve the pre-specified primary endpoint of the study (p-value=0.05).
Provenge® was rejected by the FDA because the agency does not accept a retrospective subgroup analysis to show benefit of an experimental drug. To gain FDA approval, the company who created Provenge® planned a new study on men with Gleason scores of 7 or less. However, the company continued to follow patients in the original study, and the results continue to be impressive.
Of the 75 patients who entered the trial with a Gleason score of 7 or less, those receiving Provenge® were 3.7 times more likely to be alive after 30 months; this translates into 53% of the Provenge® group staying alive compared with only 14% of the placebo group. The Provenge® group also remained pain-free twice as long on average as the placebo group.7
A Wall Street Journal editorial commented on the FDA’s deplorable delay by stating:
“We know that it works, and we know why it works. In any rational regulatory environment, that would be reason to speed Provenge® to market. But this is the FDA we are talking about.” 8
Fast forward to 2005, and the results of a new clinical study on Provenge® showed that three times as many advanced prostate cancer patients who received Provenge® were alive compared with patients receiving a placebo.9-11 This study evaluated patients with prostate cancer who had progressive disease during androgen-deprivation therapy and who were categorized as having androgen-independent prostate cancer. This patient subset has a highly adverse prognosis, with most dying of the disease within a few years. In the Provenge® study, 34% of the patients receiving Provenge® were still alive after three years, compared with only 11% of men who were randomly assigned a placebo.
FDA Condemns Placebo Group to Death
Under FDA regulations, end stage prostate cancer patients had to risk receiving no therapy (the placebo) in the hope that they might be lucky enough to be in the study arm that received the promising drug (Provenge®). Life Extension has long advocated that cancer patients with advanced disease should not have to risk receiving a worthless placebo. Historical controls could be used instead of placebos to spare such patients almost certain death.
Prostate cancer kills more than 30,000 American men every year.2 Provenge® has clearly demonstrated that it improves survival rates, yet the FDA still has not approved it. Considering that the FDA could have approved Provenge® as an experimental therapy as early as 2002, the agency’s delay in approving this one drug alone may have resulted in the premature death of tens of thousands of men.
FDA Advisory Panel Recommends Approval of Provenge®
On March 30, 2007, an FDA advisory panel reviewing all data on Provenge® recommended by a 13-4 vote that the agency approve it.12-14 The approval of Provenge® would open a new front in the war on cancer, because its mode of action is different from that of existing chemotherapy drugs and radiation. Provenge® is a personalized therapy in which some of a patient’s white blood cells are removed, programmed outside the body to attack prostate cancer cells, and then infused back into the body three or four days later.
FDA Ignores Its Own Advisory Panel
The clinical trials provided direct evidence that those who received Provenge® lived longer compared to control groups.9,15-29 According to the FDA, however, these “survival advantages” had “issues.” When these same “issues” were discussed in the Provenge® public meeting, the majority of the FDA Advisory Panel (in a 13-4 vote) thought that the issues, while relevant and important, were superseded by the solid immunology science behind the product.
Despite irrefutable data showing Provenge® extends life span, FDA bureaucrats succumbed to intense cancer establishment lobbying, and they denied approval. The FDA now insists on more data, which could take several years. This leaves those with advanced prostate cancer without a treatment that has the possibility of extending their lives.