Dendreon Provenge Could See Survival Benefit Extension

April 13, 2013

Provenge is the only immune therapy approved by the FDA for the treatment of prostate cancer. It is an expensive treatment, about $100,000 per patient, and it is only approved for asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. In other words, once prostate cancer has become both malignant and keeps growing despite testosterone being artificially lowered, and before it has become painful.

According to its Seattle-based maker Dendreon (DNDN) , Provenge will "jumpstart your immune system to fight advanced prostate cancer." Unfortunately some prostate cancer has its own tricks for defeating the immune system. As a result, in clinical trials, compared to untreated patients, Provenge therapy extends life by a median (50% of men don't get this much benefit, 50% get more) of 4.2 months. Some lucky men live much longer, including some who have now survived for years.

Finding out why some men don't respond well, and helping all prostate cancer patients live longer, is now a major medical science question. One group of doctors who may have an answer is led by Samir N. Khleif, MD, director or the Georgia Regent University Cancer Center. He believes there is good science indicating cyclophasphamide and CT-011 both inhibit prostate cancer's ability to circumvent both the body's natural immune system and therapies like Provenge.

A trial is planned in which men with metastatic prostate cancer will also take either or both cyclophasphamide and CT-011 along with Provenge. While this is an exciting theory, it should be emphasized that it will likely be a couple of years before the results are known. Then, most likely, the FDA would require a larger Phase III trial to be successful before approving the combined therapy. [See also Interview with Samir N. Khleif, MD in Renal & Urology News]

Prostate cancer is quite common in older men and generally is not a death sentence: In the U.S. 240,000 men are diagnosed annually, and about 30,000 die. Most prostate cancer victims die of some other cause, and it is difficult to predict which individuals will see their disease progress to being metastatic and castrate resistant. However, at that point it tends to be deadly. There is a broad debate over whether earlier interventions like surgery and radiation are overdone. Those who favor early treatment believe it cuts down on the number who progress to deadly disease. Those who oppose early treatment point to its cost, the low likelihood of progression being the cause of death in older men, and the complications from treatment (loss of control and occasional deaths from surgery.) Even lowering testosterone levels has side effects men don't like.

David Crawford, MD, is one of the growing number of physicians who believes that the answer may be in sequencing therapies for late-stage prostate cancer patients. He points out that in the last 3 years several therapies that are proven to help have finally been approved by the FDA, and more may be on the way. In addition to Provenge, we now have Zytiga which lowers testosterone more than previous drugs could, and Xtandi, which is an androgen receptor antagonist.

Doctor Crawford believes that for cancer in general multiple therapies have been more successful than single therapies. This is partly because cancers can develop defenses against therapies over time. By attacking prostate cancer at one, or in quick succession, with the newer therapies, Crawford believes patients will see better results. Trials are underway to determine if there is a preferred sequence for prostate cancer. [See Optimal Sequencing of the New Prostate Cancer Drugs in Renal & Urology News]

Currently doctors are divided into two camps. Some favor either Zytiga or Xtandi first because they act quickly to reduce hormone levels. Others favor Provenge first because the immune system acts over time and the cancer at this stage is already

The consensus in the community seems to be moving towards giving both types of therapy as soon as possible. As with Provenge, neither Zytiga nor Xtandi are cures, but instead, on a statistical basis, prolong the lives of the patients who take them. Xtandi prolongs life by a median of 5 months, slightly longer than the Provenge median.

Disclaimer: I own Dendreon (DNDN) stock and will not trade the stock for 7 days after the publication of this report.

William P. Meyers

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