Scientific America
June 2004
Title:
Overcoming Self
A company tries to turn the Immune System
against Cancer
by Gary Stix
Pages 40 to 41
SEVERE EDIT
Clinical trials with the drug Provenge, did not at first go according to plan. Dendreon's stock plunged in early 2002 after an analysis by a company statistician estimated that the drug might not meet the trials' goal of delaying
disease progression for patients for whom hormone and other therapies had already failed. After the 127 patient trial ended-the first ever Phase III trial of a <FONT COLOR=BLUE> dendritic cell cancer vaccine </FONT> just having missed acheiving statistical significance-researchers took a closer look at the data.
A subset of the patients, those with a less aggressive form of the disease (seven or less on the Gleason scale) had improved significantly on the therapy with only relatively minor minor side effects.
<FONT COLOR=BLUE>The additional analysis suggested that this population of patients, which accounts for 75 percent of the 75,000 men with late-stage prostate cancer (patients who had failed hormone therapy), could benefit.</FONT> But the FDA prefers not to use after-the-fact analysis as the basis for approving a drug. Investigators can analyze and reanlyze the data until they find a group of patients that seems to have gotten better. To have merit, a solid clinical trial must meet the goal, or end point, that it establishes at the outset. So Dendreon went back to the FDA and got approval to enroll an additional 275 patients whose Gleason scores registered seven or less as part of a second trial of Provenge
that was already underway.
Dendreon also continued to follow patients from its first trial. In January of this year, it reported at an industry meeting on projections that patients with the lower Gleason scores would experience a longer survival time-8.4 months more than patients receiving a placebo.
Moreover, 53 percent of the Provenge patients were still alive at 30 months, compared with 14 percent taking a placebo. The presentation sent the stock soaring and facilitated Dendreon's raising of $150 million in the public markets in January.
Cancer vaccinologists often compare their field with that of monoclonal anitbodies a decade ago, when those molecules that can, say block a specific receptor on a cell had fallen into disrepute. In recent years, monoclonals such as Rituxan (for lymphoma) and Herceptin (for breast cancer) have staged a rousing comeback,
and they now represent the vanguard of cancer therapies.
<FONT COLOR=BLUE> Not everyone concurs with this comparison. Monoclonals are often described as weapons that attack a particular target. "With a monoclonal, you have a smart bullet against cancer cells," says Matthew Geller, a senior biotechnology analyst for CIBC World Markets. "With a vaccine, you're trying to teach the immune system to go after cancer cells, something it hasn't been able to figure out in millions and millions of years of evolution."
Another cancer vaccine researcher also had qualms,
Pramod K. Srivastava, a professor at the University
of Connecticut School of Medicine and a founder
of Antigenics, a cancer vaccine company, questions
whether there is any evidence in the scientific
literature that the antigen PAP induces a protective
immune response, although Dendreon emphasizes that
the antigen must be fused with the cytokine GMCSF
and loaded into a dendritic cell to create autoimmunity.
Srivastava contends that the cytokine or the dendritic cell itself might be producing some immune response, not the PAP. "The antigen might simply be there for the ride," he says. </FONT>
yada yada yada ... the results are next year ...
END OF EDIT
note-
posting this because of the science ...
I don't own the stock or follow it ....
John |
