Dendreon CEO: rival prostate drugs to boost market

Mon Mar 12, 2012 11:17pm EDT

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(Reuters) - Dendreon Corp expects the entry of rival prostate cancer drugs from Johnson & Johnson and Medivation Inc to boost demand for new therapies, including its own Provenge, the company's new chief executive said.

"People have missed that there are a large number of patients sitting in urology offices today who don't know they have metastatic disease," CEO John Johnson said in a telephone interview. "Historically, there hasn't been an imperative to identify those patients. Now that we have new agents there is an imperative."

J&J said last week that a trial of its prostate cancer pill Zytiga in patients who had not received chemotherapy was stopped early so that those in the control group could be offered the drug after its benefits became obvious to safety monitors.

Shares of Dendreon have fallen about 9 percent since the J&J news as investors worry that Zytiga, rather than Provenge, will become the drug of choice for prostate cancer patients whose disease has stopped responding to conventional hormonal therapy. The shares ended down 2 percent on Monday.

Johnson said Dendreon still expects modest quarter-over-quarter growth for sales of Provenge this year. Analysts, on average, have projected 2012 sales of $384 million, according to Thomson Pharma.

ISI Group has estimated that around 30,000 U.S. men with prostate cancer are currently eligible for treatment with Provenge. Johnson declined to comment on Dendreon's own estimate of the Provenge-eligible population.

Hopes for future Provenge sales were sky high when U.S. regulators approved the therapeutic vaccine in April 2010 for patients with prostate cancer who had failed to benefit from hormone therapy. Some analysts had expected Provenge, which spurs the immune system to attack prostate cancer cells, to have sales in the billions.

But those forecasts have been ratcheted back.

COMBINATION WITH ZYTIGA

Zytiga, a pill, is already approved for patients after they have undergone chemotherapy, while Provenge, an injected immunotherapy, is approved in the pre-chemotherapy setting. J&J said it plans to file this year for approval of Zytiga in patients no longer being helped by hormonal therapy.

An experimental pill from Medivation and Astellas Pharma, with a mechanism of action similar to Zytiga's, has been shown to help patients with advanced prostate cancer live longer and is expected by many industry observers to also be effective in earlier-stage cancer.

Johnson said that as soon as late this year Dendreon could have the first batch of results from a trial looking at the use of Provenge and Zytiga in combination and in sequence.

He said it is possible that the pool of patients eligible for treatment with Provenge could shrink if it turns out that pre-chemotherapy patients are routinely treated first with Zytiga.

"That's not how we see it playing out, but it is a possibility," the CEO said.

Johnson was named as Dendreon's CEO last month, succeeding Mitchell Gold, who had served in that post for nearly a decade. Gold will serve as executive chairman through June, at which point he will continue as a director and Johnson will become Dendreon's chairman.

A course of therapy with Provenge, which has been shown in a pivotal trial to extend survival by 4.1 months, is priced at $93,000. Zytiga is less costly, at about $5,000 a month, usually for eight cycles, and is much easier to manufacture and administer.

JNCI STUDY

A recent study published in the Journal of the National Cancer Institute which concluded that Provenge trial patients treated with a sham infusion may have been harmed by it, making survival results for Provenge look comparatively better, was dismissed by Dendreon as without scientific merit.

"That theory was circulated a couple of years ago, when Provenge was under review for Medicare coverage," said Mark Frohlich, the company's chief medical officer, referring to the government health insurance program for the elderly.

Treatment with Provenge requires that immune system blood cells be removed from the patient, treated with a prostate antigen and stimulating factor, then infused back into the patient. In the original trial of Provenge, patients in the comparison group went through the same process, but were re-infused with untreated cells.

Frohlich said the authors of the latest study failed to acknowledge that the massive volume of lymphocytes circulating in the body means the number removed from patients during the trial was between just 0.3 and 1.4 percent of that total.

"If you ask any immunologist, it's not really biologically plausible that those patients were immunologically depleted," Frohlich said.

Prostate cancer kills about 250,000 men a year globally and is the second most common cause of cancer death in men in the United States, after lung cancer.

"I do think this issue around the growth of the market and the benefit of having multiple companies working in the urology space is one that has been underappreciated," Johnson said.

(Editing by Gary Hill, Tim Dobbyn and Muralikumar Anantharaman)

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Comments (2)
jra wrote:
It should be noted that this Zytiga trial was stopped even though overall survival (OS) for the drug was not found to be statistically significant according to a J&J spokesperson. OS was one of the two primary endpoints for this trial, and continuing the study may have been perceived as a futile pursuit by the Data Monitoring Committee. Progression free survival (PFS), as measured by a reduced doubling time in PSA levels, was, as expected beforehand, statistically significant. It is debatable if patients in the control arm would want to cross over given the apparent inability of Zytiga to extend survival in this space for which Provenge is the standard of care.

Mar 13, 2012 1:06am EDT  --  Report as abuse
MarieHuber wrote:
Information re accuracy of quoted statements:

“In the original trial of Provenge, patients in the comparison group went through the same process, but were re-infused with untreated cells.”
— Only 0-12% of the cells removed from the comparison group were reinfused. 65% of cells were lost during initial cell processing (as for Provenge patients), then a further 2/3 (23% of starting number) were removed and frozen for possible later use. The remaining cells were placed in the fridge for 40+ hours, and no checks of their viability were reported, so it is not known how many died at this stage. Thus, at best placebo patients received 12% (median) of their originally-removed cells back, and at worst they received an infusion of dead cells.

“Frohlich said the authors of the latest study failed to acknowledge that the massive volume of lymphocytes circulating in the body means the number removed from patients during the trial was between just 0.3 and 1.4 percent of that total.”
— The body’s 500 billion lymphocytes are by no means freely “circulating”. Lymphocytes express particular receptors which determine which endothelia various subtypes can cross, targeting and confining cells to specific tissues and organs. Several experiments demonstrate that lymphocytes are not a single freely-equilibrating pool. The proportion that blood lymphocytes represent of the body’s total is irrelevant when considering the repeated depletion of 95% of them from the peripheral circulation of elderly patients with metastatic cancer with 0-12% returned 3-4 days later.
The 3 placebo treatments lost a net 20 billion lymphocytes (median, plus 6 billion monocytes, median) from those patients.

“If you ask any immunologist, it’s not really biologically plausible that those patients were immunologically depleted,” Frohlich said.
— It is certainly biologically plausible that the repopulated lymphocytes in these elderly patients differed significantly from those which were removed. Immunologists with expertise in immune aging are those best qualified to speak to the many ways in which the post-treatment immune system may have been impaired.

Mar 13, 2012 1:30pm EDT  --  Report as abuse
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