) -- Investors mindful of competitive threats to
newly launched prostate cancer therapy Provenge may have less to fear from
experimental pill zibotentan.
The survival benefit reported earlier in a phase II prostate cancer study of zibotentan has narrowed and is no longer statistically significant, according to a new and final analysis of the study published in a medical journal last week.
This makes it more likely that a closely watched phase III study of zibotentan won't produce results strong enough to knock Dendreon's Provenge from its perch as the king of newly approved prostate cancer therapies.
AstraZeneca is expected to announce top-line results from the phase III zibotentan study in the fourth quarter.
Dendreon fans have been somewhat worried about zibotentan because the drug is being studied in the same type of advanced, hormone-refractory prostate cancer patients who are, right now, eligible for treatment with Provenge, making the drugs direct competitors were zibotentan to be approved.
Moreover, zibotentan is a pill taken once a day, making it more convenient and likely less expensive than Provenge -- a personalized vaccine requiring special manufacturing and three infusions over the course of one month.
Zibotentan earned a certain amount of attention in 2007 when an interim analysis of the randomized, controlled phase II study demonstrated a median survival benefit of seven months compared to a placebo. By comparison, Provenge demonstrated a median four-month survival boost in the phase III study that won the drug approval earlier this year.
recently won approval for a new prostate cancer drug and
Johnson & Johnson
has its own prostate cancer drug in development that recently posted positive phase III results, Yet compared to AztraZeneca, neither company is seen as much of a near-term direct threat to Dendreon because use of their respective drugs at least initially, is directed towards patients with more advanced disease and after Provenge treatment.
Zibotentan's credibility as a Provenge killer took a hit last week after researchers published a final analysis of the phase II study in the
British Journal of Urology
, showing zibotentan to be not as effective as previously thought.
At the final analysis conducted in December 2008, patients treated with the higher, 15 mg dose of zibotentan had a median overall survival of 23.9 months compared to a median overall survival of 19.9 months in patients treated with a placebo.
That four-month survival benefit for zibotentan was not statistically significant and was lower than the statistically significant, seven-month survival benefit recorded at an interim analysis of the trial conducted in February 2007.
Overall survival was actually a secondary endpoint in the zibotentan study. The drug also failed to achieve the study's primary endpoint of time to disease progression.
In the study article, researchers note the narrowing of the zibotentan survival advantage over time but say one possible explanation is that doctors in the study stopped treating patients with the drug too soon.
"While these data do make us less worried about zibotentan as a competitive threat, they do not remove that worry," wrote Biotech Stock Research's David Miller in a note sent last week to subscriber's of his biotech investment newsletter. Miller is a long-time Dendreon bull.
"We've always said we expected the phase III ENTHUSE M1 Trial would see a narrowed median survival advantage from the 7.2 months. Now we're potentially talking about a narrowing from 4 months. If zibotentan's median survival number is noticeably less than 4 months (say below 3.6 months) even insurers would be hard pressed to make the case zibotentan should come first," Miller added.
AstraZeneca's is conducting three phase III studies of zibotentan in prostate cancer, the first of which goes by the moniker ENTHUSE M1.
Zibotentan works by blocking receptors on prostate cancer cells that help tumors grow and survive. The FDA rejected the approval of a similar drug developed by
Provenge is a cancer immunotherapy that trains a patient's own immune system to identify and destroy prostate cancer cells.
--Written by Adam Feuerstein in Boston.
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Adam Feuerstein writes regularly for TheStreet.com. In keeping with TSC's editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet.com. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback;
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