Medivation, Inc. and Astellas Pharma Inc. announced positive results on all efficacy endpoints from the Phase 3 AFFIRM trial of the investigational drug MDV3100 in men with prostate cancer previously treated with chemotherapy. 

“MDV3100 outperformed our expectations in the AFFIRM trial by meeting the primary and secondary endpoints with strong statistical significance and demonstrating a favorable safety profile,” said Howard I. Scher, M.D., chief, Genitourinary Oncology Service at Memorial-Sloan Kettering Cancer Center, and the co-principal investigator of the AFFIRM study.  “These results, together with its convenient once-daily oral dosing regimen, should make MDV3100 a promising option for men with prostate cancer who have received prior hormones and chemotherapy.”

Of particular note: 

• Men taking MDV3100 lived for a median of 18.4 months, compared with 13.6 months for men taking placebo (p<0.0001; HR=0.631).
• MDV3100 also met all secondary endpoints, including radiographic progression-free survival (8.3 versus 2.9 months; p<0.0001; HR=0.404), soft tissue response rate (28.9% versus 3.8%; p<0.0001) and time to prostate-specific antigen (PSA) progression (8.3 versus 3.0 months; p<0.0001; HR=0.249). 
• PSA declines of 50% or greater were more common in the MDV3100 group than in the placebo group (54.0% versus 1.5%; p<0.0001), as were PSA declines of 90% or greater (24.8% versus 0.9%; p<0.0001).
• MDV3100 was well tolerated.  Common side effects included fatigue, diarrhea and hot flush.  Serious adverse events, adverse events causing patients to stop treatment, and adverse events causing death all were lower in the MDV3100 group than in the placebo group.  Grade 3 or greater side effects of interest were fatigue (6.3% in the MDV3100 group versus 7.3% in the placebo group), cardiac disorders (0.9% versus 2.0%) including myocardial infarction (0.3% versus 0.5%), seizure (0.6% versus 0.0%) and liver function test abnormalities (0.4% versus 0.8%).

“The almost five-month overall survival benefit MDV3100 showed over placebo in this trial is noteworthy, as is the fact that men with post-chemotherapy prostate cancer taking MDV3100 lived for a median of a year and a half,” said Professor Johann de Bono, M.D., MSc, Ph.D., FRCP, Honorary Consultant in Medical Oncology, Professor of Experimental Cancer Medicine, The Institute of Cancer Research and The Royal Marsden Hospital, and the co-principal investigator of the AFFIRM study.  “As a practicing oncologist, I am hopeful that I may be able to offer MDV3100 as a life-prolonging option to these very ill patients.”

“The robust overall survival data produced in the AFFIRM trial by MDV3100, the first androgen receptor signaling inhibitor, clinically validate this novel mechanism of action in treating men with prostate cancer who have received prior chemotherapy,” said David Hung, M.D., president and CEO, Medivation.  “We and our colleagues at Astellas are committed to working diligently to bring MDV3100 to patients as quickly as possible.”

“First of all, we’d like to thank both the investigators and patients for their contributions to the AFFIRM trial, as these results are an important step toward making this potential new treatment available to patients with prostate cancer,” said Steven Ryder, M.D., president, Astellas Pharma Global Development.  “MDV3100 is a significant contributor to our strategy of becoming a global category leader in oncology.  We’re delighted to be collaborating with Medivation on MDV3100 at this critical juncture.”

Date: January 31, 2012
Source: Medivation, Inc.