Harbor BioSciences, Inc. a biopharmaceutical company developing novel therapeutics for the treatment of cancer, metabolic and inflammatory diseases, announced it is closing the clinical sites of its US-based phase I/II a 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/II a 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 analogue of a testosterone metabolite, has been found to induce cell death (apoptosis) in prostate tumours. 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: US 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. Anti-tumour effects were noted in all doses studied including the lowest dose. In some individuals, there have been favourable responses in bone scans ranging from decrease of tracer uptake to resolution of some bone tumours; 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 Tumour Cells (CTC). For patients who at baseline have favourable CTC counts (< 5), the majority remains favourable at 4 weeks (86.2%) and for those with CTC enumeration at 12 weeks (84.2%). Furthermore, for those patients with unfavourable CTC (= 5), 26% become favourable at 4 weeks and for those with counts at 12 weeks 62.5% become favourable. 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-tumour 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 II b 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.
Harbor BioSciences is a development-stage company with two product candidates recently in clinical trials: Apoptone (HE3235) in the cohort expansion portion of a phase I/II a trial of patients with late-stage prostate cancer, and Triolex (HE3286), has completed phase II a trials in obese type 2 diabetes mellitus patients.