conference date: May 31, 2007
At Bank of America 2007 Health Care Conference
Overview: Explained results of talks to FDA about criteria for allowing Provenge to market. FDA has agreed prior submitted data showed survival benefit. They agreed that interim data from continuing study due in 2008 can be sufficient for marketing approval.
Immune response from Provenge [sipuleucel-T], an active cellular immunotherapy, is persistent. Antigen delivery cassette is key to the technology; uses recombinant protein for a well-validated antigen. Covered basics of how therapy works and manufacturing of the therapy, including collection of each patient's antigen presenting cells from blood. They have a potency assay for the cassettes to be sure the process has worked. The process is well controlled and has been replicated over 2000 times for clinical trials. Actual infusion takes thirty to sixty minutes; they get three infusions over a one month period. Extremely well tolerated by patients.
Addressable market: for androgen-dependent cancer 30 to 40% of patients fail primary therapy. These go to hormonal manipulation therapy. All eventually fail hormone therapy, becoming androgen-independent. These have asymptomatic, metastatic, androgen-independent prostrate cancer. Provenge is for them. There is currently only one drug approved for this condition, docetaxel, which has a 2.5 month average survival benefit. Typical survival without therapy is 18 to 20 months. Majority of patients reject this chemotherapy because of the quality of life issues versus the slight survival benefit.
First Phase III study 9901 with 127 men showed a 31% delay in time to disease progression, the primary endpoint (P=.052, hazard ratio 1.45). Also required following subjects for 3 years for survival. Overall survival showed 41% reduction in risk of death, 4.5 months median survival benefit (P=.01, hazard ratio 1.7). This was the focus of the application and advisory committee opinion given in March 2007. But in addition long term (3 years) follow up showed 34% in drug arm alive versus 11% alive with placebo. Adverse events were fevers and chills in 30 to 60% of patients.
9902a study was underpowered and stopped early. Integrated analysis include 225 patients with 3.3 months median survival benefit. (hazard ratio 1.3, P=.331). There were imbalances that after adjustment gave a P= .023.
Combined 9901 and 9902a study data showed 225 patients, 4.3 months median survival benefit, 1.5 hazard ratio, P=.01.
May 8 complete response letter requested additional efficacy data. At most recent meeting with FDA they agreed BLA contains data that shows Provenge prolongs survival. FDA agreed that either a positive interim or final analysis for survival as described by the Impact, or 9902b ongoing study special protocol will be sufficient for licensing of Provenge.
Interim results from ongoing Impact study expected next year.
Design of continuing Impact study similar to 9910 (double blind, randomized), but enrolling 500 men with asymptomatic, metastatic, androgen-independent prostrate cancer. Primary endpoint is overall survival, secondary endpoint time to disease progression. Conducted under special protocol agreement with FDA. Modeled after combined prior Phase III studies. Well powered for interim analysis because interim will have more than 164 death events and assumed a lower hazard ratio. Patient profile is important (how sick patients are to begin with); will use Halabi model to predict survival of patients when they enroll.
132,000 men have androgen-independent prostrate cancer. About 96,000 of them have metastatic disease. Our label (type Dendreon is asking FDA to licenses Provenge for) is 55,000 men with asymptomatic, metastatic, androgen-independent prostrate cancer.
Urologists and Oncologists debate which type of doctor are best equipped to do infusions. Requires about 125 sales reps.
Have data showing potential for earlier stage prostate cancer, but will have to do clinical trials to get approval for it.
Antigen cassette immunotherapy system is ready to be tried on other types of cancers with other antigens.
Has $88 million in cash and equivalents. For full fiscal 2007 expects total $95 million cash burn; minimizing that by restructuring work force. Many costs are tied to third party charges from trial. These will be reduced in 2008, so $55 million of 2008 cash burn. Has completed commercial scale inventory build and it has a multi-year life span. Manufacturing facility is operational and ready to go; current trial therapy is manufactured in plant.
Has potential to be first-to-market with cancer active cellular immunotherapy. Owns 100% of world-wide rights. Can expand Provenge to earlier and later stage of disease. Can try platform with other types of cancer.
Expanded access for compassionate use? We don't have the resources for that, so there are no plans for that. Best way to bring to patients is to complete the regulatory process.
Unusual for FDA to go against one of its advisory committees. Can you now tell us more about the reason for the data package rejection? Survival benefit was compelling but not primary endpoint of study. Availability of Impact study to answer FDA questions definitively. Human factors in FDA decision making as well.
Interim analysis P-value and alpha spend problem? Based on 9901 and 9902a, which had 164 death events. Interim analysis will have more than 164 death events. Hazard ration for integrated was 1.5. Impact study was chosen to be less. Enrollment is strong and will be completed this year. Interim is spending a fair amount of alpha compared to other interims because they have a good handle on analysis plan.
Halabi model? Well known model in prostate cancer for predicting overall survival. Used to make sure they have comparable patient demographics.
Second trial was stopped early? Stopped in 98 men when impact study was started. These studies were designed to be integrated together.
Interim P value required to stop trial? Overall alpha is .05, to be divided between interim and final analysis. Interim has a fair amount of power associated with it partly because it started enrollment in 2003.
Believes results will come in between the middle and second half of 2008. Data won't be released unless study is stopped with positive outcome. Could also stop for futility.
Hazard ratio is the same for interim and final analysis.
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