No Devil in Details: Dendreon Data Stands Up to Scrutiny from Doctors, Investors

4/28/09Follow @xconomy

Suspense has been building for two weeks about just how good Dendreon’s big clinical trial results were going to be, and when the results finally came out today, fans of the company had nothing to be disappointed about.

Earlier in the day, we reported what readers needed to remember about the context of this trial, and then we reported the most essential facts when the data appeared. A clinical trial of 512 men, called Impact, showed that patients lived a median time of 25.8 months if they got Provenge, Dendreon’s experiemental immune-booster, compared to 21.7 months for those on a placebo. This finding represents a 4.1 month advantage in median survival on the drug. The p-value, which tells statisticians whether this might have been due to chance, was 0.032, which is well within the FDA’s threshold to certify the finding as legitimate. Side effects were mostly fever and chills that lasted one or two days after injections.

Dendreon provided much more extensive detail on this trial in a conference call today with analysts, but there was nothing groundbreaking or revelatory beyond what David Penson of USC presented earlier in the day at the American Urological Association meeting in Chicago. Dendreon CEO Mitchell Gold didn’t back off at all from his statement a couple weeks ago that the data was “unambiguous” and a “clear hit.” But I felt the need to follow up with this story to provide a few more details and look ahead at some of the business strategies that will become more important as this year goes on.

This trial matters more than most, and generates way more headlines, because it is the first time after decades of research that scientists have shown an ability to stimulate the immune system to fight cancer cells like a virus. This new mode of treatment is called an immunotherapy, or sometimes a cancer vaccine. It’s also a big step forward for treatment of prostate cancer, which kills about 30,000 men every year in the U.S., and is currently treated with chemical castration, and in the terminal stages, a form of chemotherapy called docetaxel (Taxotere) that has nasty side effects most men would prefer to avoid. Some people balked at why trading in the stock suddenly fell 45 percent before the announcement, but there was nothing in the data to explain why that happened. After hours, the shares recovered, climbing to $27.22 a share, according to this Bloomberg News story. One doctor told the Wall Street Journal that “We’ve been waiting a long time,” for a drug with a profile like Provenge.

“This is a historic day for the company, and a great day for prostate cancer patients,” Gold said.

So Provenge has been eagerly anticipated by patients for years. Chief medical officer Mark Frohlich walked through most of the data on the call for analysts. Here are the highlights:

—Patient demographics in terms of age, race, and tumor status were about the same among patients who were randomly assigned to get Provenge or a placebo when they entered the study. That means the survival benefit couldn’t have been explained by Provenge patients being healthier when they entered the study.

—The Kaplan-Meier survival curves showed the effect of the drug started early in the study, and stood the test of time.

—The company looked retrospectively for any abnormalities in subpopulations who might have done really well and skewed the overall results in favor of the drug. That analysis showed that all subpopulations of people on Provenge, regardless of their tumor aggressiveness, locations, and PSA diagnostic scores showed a consistent survival benefit, Frohlich said.

—The study failed to show a statistically significant benefit on a secondary goal—whether Provenge could help slow the spread of prostate cancer tumors. This matched up with the prior trial, and shows that slowing tumors isn’t necessarily a reliable predictor of whether a drug can help patients live longer. The measurement is difficult to measure reliably, which is one reason why it wasn’t the main goal of the study, Gold said.

—A little more than half of Provenge patients (54.1 percent) developed mild to moderate chills, compared with 12.5 percent on the placebo. Fever was the next most-common side effect, with 29.3 percent of patients reporting that event, which typically went away in one to two days, which is consistent with prior Provenge studies, Frohlich said.

—The number of serious adverse events in the study was almost identical between the Provenge group (24 percent) and the placebo group (23.8 percent). There were more serious fevers and pulmonary embolisms in the Provenge group, and there were more cases of pneumonia and deep vein thrombosis in the placebo group, although the overall numbers were small for all those effects.

—Patients in the placebo group were allowed to “cross over” and get a frozen form of Provenge after their disease progressed, because even though it might muddy up the waters of the trial, it would be unethical to deny a dying patient of a drug that might work. This sort of clinical trial design, assuming that Provenge is effective, might make the placebo arm appear to be doing better than it really is, and reduce the advantage for the Provenge group. Now that the trial is completed, all patients are eligible to get regular Provenge, Frohlich says.

The company plans to take its time to scrub through the records from the trial carefully as it prepares to turn in an amended application to the FDA in the fourth quarter of the year, Gold says. The FDA will then have as long as six months to complete its review of the application, he said.

Lots of questions about the business strategy are still to come, and Gold deferred most of them to an analyst day the company plans to host this summer. In terms of finding a partner, Gold repeated that the company hopes to market this product by itself in the U.S., and find a partner to help with winning regulatory approval and marketing overseas. The company also sees the Provenge method as validating its technology, which can be applied across a platform of other cancers, namely breast, colon, bladder, and kidney, Gold said.

“Clearly the people who treat this disease are excited about the data,” said David Miller, CEO of Biotech Stock Research, a Seattle-based research firm that began recommending Dendreon stock in 2001. “There are some people out there who still want to pick on it.”

News reports are pouring out of Chicago as some more skeptical doctors question how meaningful a median survival advantage of 4.1 months really is. Some might eventually raise a fair point of whether the drug is going to be cost-effective, given that it will undoubtedly cost in the tens of thousands of dollars per patient. Questions like that, and whether Dendreon can manufacture the drug efficiently enough to meet demand, hire the right people to market it cleverly, and win over some of the skeptics in oncology, are sure to be on Dendreon’s mind for months to come.

But those are all questions for another day. Tonight, Dendreon is hosting a party at a hotel in Chicago.

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