Medivation, Inc. (MDVN) announced that its on-going clinical trial (phase I & II) of MDV3100 in castrate resistant prostate cancer has demonstrated both efficacy and safety in its current trials. The drug under study, MDV3100, is novel androgen receptor antagonist. This trial tracked 114 prostate cancer survivors who are hormone resistant (CRPC) for 12 weeks or longer, and show that MDV3100 consistently demonstrated “encouraging anti-tumor activity” across dose levels and endpoints.

Howard Scher, M.D., principal investigator of the trial and chief of the Genitourinary Oncology Service and the D. Wayne Calloway Chair in Urologic Oncology at Memorial Sloan-Kettering Cancer Center said, “These men have a limited life expectancy, and currently their only approved treatment option is chemotherapy.” They indicated they look forward to the phase III trial and hope to see the trial in development this year.

The men participating in the trial had progressive disease upon enrollment and were heavily pretreated, with 77 percent having failed at least 2 lines of prior hormonal therapy and 43 percent having also failed one or more chemotherapy regimens.

Efficacy endpoints in the study included circulating tumor cell (CTC) counts, serum prostate specific antigen (PSA) levels, soft tissue and bony metastases, and time on treatment.

Almost all of the men who had favorable CTC counts (four or less) at the start of treatment maintained these favorable counts at week 12 (89 percent of chemotherapy naive patients and 100 percent of post-chemotherapy patients). Even more interesting was that a significant number of the men with unfavorable CTC counts of five or higher at baseline converted to favorable counts of less than five at week 12 (73 percent of chemotherapy naive patients and 40 percent of post-chemotherapy patients). This CTC conversion rate is encouraging in light of a recently published study in the October 2008 issue of Clinical Cancer Research, in which post-treatment conversion to a CTC count below five was associated with a 15-month survival benefit in castration-resistant prostate cancer patients.

The trial drug, MDV3100 also produced significant PSA declines (50 percent or more from baseline) and radiographic control (partial response or stable disease) in both chemotherapy naive and post-chemotherapy patients at week 12.

Thus far, the median time on treatment for chemotherapy-naive patients and post-chemotherapy patients is 276 and 145 days, respectively.

MDV3100 has been generally well tolerated at doses of up to and including 240 mg/day. The most frequently reported adverse event was fatigue. Two witnessed seizures occurred in men taking doses of 600 mg/day and 360 mg/day. Both men were taking concomitant medications that can cause seizures. A possible but not witnessed seizure was reported in a man taking a dose of 480 mg/day.

The new MDV3100 efficacy and safety data will be presented in a poster session on Friday, February 27 at 11:45 a.m. Eastern Time at the American Society of Clinical Oncology’s (ASCO) 2009 Genitourinary Cancers Symposium in Orlando, Fla.

Joel T Nowak MA, MSW