Harbor BioSciences closes U.S.-based Apoptone Phase I/IIa clinical trial for castration resistant prostate cancer

Feb 7 2011

Harbor BioSciences, Inc. (OTCBB:HRBR), a biopharmaceutical company developing novel therapeutics for the treatment of cancer, metabolic and inflammatory diseases, today announced it is closing the clinical sites of its U.S.-based Phase I/IIa clinical trial with Apoptone® (HE3235) for castration resistant prostate cancer (CRPC) – also referred to as hormone resistant prostate cancer. The final statistics for the study will be generated after all sites have been closed and the database is locked. The results are not expected to change significantly from the company's September 2010 update. The Phase I/IIa data, which will include the final statistical analysis, will then be transferred to the China State Institute of Pharmaceutical Industry (CIPI), Harbor BioSciences' development partner. That partnership was announced on January 19, 2011.

Apoptone, a novel steroid analog of a testosterone metabolite, has been found to induce cell death (apoptosis) in prostate tumors. The dose-response study was designed to determine safety, maximum tolerated dose and biological activity of Apoptone in both taxane-resistant and chemotherapy-naïve patients with CRPC. The study was conducted with the Prostate Cancer Clinical Trial Consortium (PCCTC) and other clinical sites. Harbor BioSciences recently received a patent for the use of Apoptone in treating breast and prostate cancer: U.S. Patent No. 7,863,261; and patent applications are pending in various foreign countries. Patent applications for formulations and solid-state forms of the compound are also pending.

A total of 68 patients were treated with Apoptone at doses ranging from 10 to 700 mg per day. The drug was judged to be safe and well tolerated. Antitumor effects were noted in all doses studied including the lowest dose. In some individuals, there have been favorable responses in bone scans ranging from decrease of tracer uptake to resolution of some bone tumors; and in one patient there was a sustained partial response (RECIST) for greater than six cycles following the first evaluation at cycle two. 

Data, analyzed using standard methodology for prostate cancer research, demonstrate an effect on circulating tumor cells (CTC). For patients who at baseline have favorable circulating tumor cell counts (< 5), the majority remains favorable at 4 weeks (86.2%) and for those with CTC enumeration at 12 weeks (84.2%). Furthermore, for those patients with unfavorable CTC (greater than or equal to 5), 26% become favorable at 4 weeks and for those with counts at 12 weeks 62.5% become favorable. CTC enumerations below 5 are associated with increased survival.

One patient at the highest dose group (700 mg) experienced a drug-to-drug interaction with simvastatin that resolved after cessation of both drugs and had not been observed at lower doses. Because anti-tumor activity has been seen at all dose levels, and a qualitative difference in this biological activity at even higher doses is not expected, the company concluded that further dose escalation represents a safety concern and that the trial has provided sufficient information to proceed to a Phase IIb study with a suitable partner. Additional clinical trials will also be conducted by CIPI in China and Hong Kong; and with a suitable partner(s) elsewhere, Harbor BioSciences will use CIPI's data to support these further development efforts.