Medivation, Inc. has announced the presentation of new efficacy and safety data from an ongoing Phase 1-2 clinical trial of the Company's novel androgen receptor antagonist MDV3100 in castration-resistant prostate cancer (CRPC) patients.
The new efficacy data cover all 114 patients who have been followed for 12 weeks or longer, and show that MDV3100 consistently demonstrated encouraging anti-tumor activity across dose levels and endpoints.
"The data thus far suggest a favorable benefit/risk ratio for MDV3100 in treating castration-resistant prostate cancer patients," said 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. "These men have a limited life expectancy, and currently their only approved treatment option is chemotherapy. Given these encouraging results and the large unmet medical need for men with castration-resistant prostate cancer, I am enthusiastic about working with Medivation to advance MDV3100 into Phase 3 clinical development this year."
All patients had progressive disease upon enrollment and were heavily pretreated, with 77 percent having failed at least two 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 patients with favorable CTC counts (four or less) at the start of treatment maintained favorable counts at week 12 (89 percent of chemotherapy naive patients and 100 percent of post-chemotherapy patients). Importantly, a significant number of patients 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.
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, as follows:
PSA response > 50% Radiographic Radiographic control: soft control: bony tissue lesions lesions Chemotherapy naive 57 percent 80 percent 61 percent Post-chemotherapy 45 percent 70 percent 64 percent
Thus far, the median time on treatment for chemotherapy-naive patients and post-chemotherapy patients is 276 and 145 days, respectively.
The new safety data include all 140 patients enrolled in the trial. 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 patients taking doses of 600 mg/day and 360 mg/day. Both patients were taking concomitant medications that can cause seizures. A possible but unwitnessed seizure was reported in a patient taking a dose of 480 mg/day.
"We are pleased to continue to see concordance of data across endpoints -- CTC changes, PSA declines, radiographic findings and time on treatment," said David Hung, M.D., president and chief executive officer of Medivation. "We continue to move forward with clinical development of MDV3100 and expect to seek U.S. Food and Drug Administration approval to advance to a pivotal Phase 3 registration study this year."