Note: This was an analyst conference to discuss the release of data from the Provenge IMPACT clinical trial. This is a detailed summary, not a transcript of the full conference.
Overview: The data appears to be slightly stronger than the levels set by the FDA for the approval of Provenge for metastatic prostate cancer.
IMPACT Study met prespecified endpoints.
Data presented at American Urology Association conference. Average increase life time was 4.1 month. There was a 38% 3 year survival increase compared to placebo. 22% reduction of risk of death, or a Hazard ratio of 0.78. For the placebo arm median survival was 21.7 months, for Provenge it was 25.8 months.
Provenge is sipuleucel-T, an autologous active cellular immunotherapy against prostate cancer.
There were 512 asymptomatic or minimally symptomatic metastatic androgen independent prostate cancer patients in the study. Life expectancy at entry had to be at least 6 months. Castrate levels of testosterone had to be achieved. Statistical P value prespecified with FDA at <0.043. Actual P = 0.032
Ruled out the possibility that survival benefit was due to a subgroup difference with placebo group.
Multiple sensitivity analyses confirmed P values and Hazard ratios.
Time to progressive disease progression (secondary endpoint) was not statistically significant.
Safety profile was consistent with earlier results; mostly headaches, chills, and fever the day following treatment. Less than 10% developed influenza type symptoms, hypertension or hyperhydrosis (sweating). Placebos had 23.8% serious adverse events, Provenge arm 24.0%. But placebo arm had much less mild adverse events.
D9901, D9902A, and IMPACT study had every similar results. Integrating them all gave a Hazard ratio of 0.735, p value 0.001, median survival benefit 3.9 months, and 33% 36 month survival v. 20% for placebo.
Placebo arm survivors can now be given Provenge.
Will apply for licensing this year in U.S.
Conclusion: Results are unambiguous. First active immunotherapy to demonstrate overall survival. Highly favorable benefit to risk profile. Short therapy duration. Could create a new oncology treatment paradigm; platform could be applied across different cancers.
Why can’t you file sooner with FDA? This study has been going on almost 6 years. We need to put together the best amendment we can. It is a type 2 resubmission, giving the FDA 6 months to review it.
Other cancers? Will be evaluating, will update you this summer.
Why 3 infusion maximum? P11 study in early stage prostate cancer showed immune systems had a persistent response against antigen. Did get an increase with boosting infusion. This was 1999. There is no reason to not give more infusions, it was just not part of the study design.
Any side effects statistically significant? Yes, the ones listed were significant.
Median survival results for placebo crossing to Taxotere? Subgroup analysis can be misleading. But we believe there is a benefit to crossover arm.
Partnering for global sales? Our goal is to keep the product for ourselves in U.S. Get a partner ex-U.S. There has been a lot of interest, we have nothing to say so far.
Medians on time to progression? 14 weeks.
This study was not designed to be a comparison study of Taxotere (docetaxel). It has a 2.5 month survival improvement. So Provenge is safer and more effective, and requires less infusions.
Taxotere after Provenge data? We may get some data on that, but have nothing to share at this time.
PSAs were not measured after patients progressed. In androgen independent prostate cancer, PSA does not correlate with survival.
Trend in pain direction? Pain was not an end point after the study was amended.
Time to progression is a difficult to measure statistic, highly subjective. So it is an unreliable endpoint.
48 month rejoin of trends? All survival curves come together eventually. At the tail end of the curve there are very few living patients, so a lot of variability.
Link to Dendreon April 28, 2009 Press Release
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