Harbor BioSciences Apoptone(R) for Prostate Cancer Shows Activity at All Doses Tested

CHICAGO, June 7, 2010 (GLOBE NEWSWIRE) -- Harbor BioSciences, Inc. HRBR today presented new positive data from its ongoing Phase I/IIa clinical trial with Apoptone® (HE3235) for castration resistant prostate cancer (CRPC) – also referred to as hormone resistant prostate cancer – at the American Society of Clinical Oncology (ASCO) Annual Meeting. The most current results from this study included data on the 100 mg cohort of chemotherapy-naive patients indicating a median time to progression of greater than 16 weeks with 80% remaining on treatment, new cohorts of patients tested at the highest dose of 350 mg, and indication of activity at all dose levels including the lowest dose of 10 mg. As no dose-limiting toxicity has been found to date, the trial continues to accrue patients, with a dose escalation group that will receive 700 mg/day.

A novel steroid analog of a testosterone metabolite, Apoptone has been found to induce cell death (apoptosis) in prostate tumors. The dose-response study reported on today was designed to determine safety and time-to-disease progression for both taxane-resistant and chemotherapy-naive patients with CRPC; and is being conducted with participating sites including the Prostate Cancer Clinical Trial Consortium (PCCTC).

Howard Scher, M.D., Chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center and Principal Investigator of the PCCTC, commented, "Conventional treatments for prostate cancer, such as hormone therapy, do not adequately prevent disease progression in some patients. This new treatment appears to induce apoptosis and therefore could potentially provide a complementary approach to hormone therapy in these patients."

The Phase I/IIa trial is an open-label study with the primary objective of assessing safety, tolerability, pharmacokinetics and activity of Apoptone in men with CRPC and an ECOG performance status score of less than or equal to 2 (ambulatory and capable of at least self-care). Patient cohorts are defined by oral daily doses of 10, 20, 30, 50, 100, 200 and 350 mg. Subjects are treated on 28-day cycles until toxicity or disease progression; CT and bone scans are obtained every two cycles to assess progression. Responding patients in both the chemotherapy-experienced and chemotherapy-naive groups will continue to be offered treatment under the current protocol.

Bruce Montgomery, M.D., Associate Professor, Department of Medicine, Division of Oncology, University of Washington School of Medicine, and lead investigator of the ongoing Phase I/IIa clinical trial, presented the updated Apoptone data on June 7 as part of the scientific program of the ASCO annual meeting, with the results described below.

"We are quite satisfied with the disease stabilization we have seen with Apoptone in late-stage patients, and consider this another exciting drug in the new class of hormonal agents that promise a meaningful change in the paradigm for treating men with CRPC," Dr. Montgomery said. 

Apoptone Phase I/IIa Clinical Study Update

Taxane-Resistant Patient Group

To date, 42 taxane-resistant prostate cancer patients with progressive (metastatic) disease have enrolled into the clinical trial at 7 dose levels. Of these, 28 (67%) reached the first reassessment (two 28-day cycles), 16 (57%) of these had stable disease or improvement of metastatic soft tissue and/or bone lesions by imaging and have received 1 to 8 additional treatment cycles before disease progression. Four patients continue to receive treatment. These include patients who are taxane resistant and who failed prior hormonal, chemotherapy and/or experimental forms of therapy including Abiraterone and MDV-3100. Prior treatment with ketoconazole (41.5% of patients) had no effect on the activity of Apoptone to stabilize disease. The drug has been well tolerated and dose escalation has proceeded to 350 mg per day with no overt dose-limiting toxicities observed. Dose escalation to 700 mg per day (350 mg BID) of Apoptone is planned.

The Kaplan-Meier estimate ⁽¹⁾ for the median time to progression in evaluable taxane-resistant patients is 15.9 weeks (range 8-24) in this ongoing trial. Due to early signs of activity, the 20 mg dose group was expanded to include 14 patients for whom the data are complete. Eleven of these were evaluable with an actual median time to progression (TTP) of 20 weeks (range 8-28). At the initiation of therapy, Apoptone induced a disease flare in some patients, which can be mistakenly interpreted as disease progression. Progression was assessed by the Prostate Cancer Working Group 1 (PCWG1) criteria, which does not account for disease flares. Disease flares are not uncommon at the initiation of therapy for metastatic prostate cancer.

 "Use of PCWG1 response criteria appears to lead to an underestimation of the TTP in the taxane-resistant patients in this dose escalation study," commented Dwight R. Stickney, M.D., Chief Medical Officer of Harbor BioSciences. "Consequently, the pre-chemotherapy patients are evaluated for progression with the PCWG2 response criteria, which accounts for disease flares. We believe 18 of the 42 patients may have been prematurely removed from the study without confirmation of disease progression, as required by the PCWG2 recommendations."

Dr. Montgomery explained, "Previously, Halabi, et al, reported TTP for this group based on PSA progression, indicating that subjects who did not progress in three months doubled their survival, . We are very pleased to see that 80% of our subjects are not progressing by PCWG2 criteria, with an actual median time to progression of greater than16 weeks."

Chemotherapy-Naive Patient Group

Eleven chemotherapy-naive patients were enrolled into an expansion group receiving 100 mg of Apoptone per day. Ten of these patients reached their first reassessment at eight weeks with stable disease and have received one to four additional cycles of Apoptone. Using the PCWG2 criteria for progression, the median time to progression has not been reached and is currently greater than 16 weeks with 8 of the 10 patients remaining on study. To assess dose response, a second group of 8 chemotherapy-naive patients has been enrolled into the study at a dose of 350 mg per day. The 350 mg group will include up to 10 chemotherapy-naive patients in order to observe tolerability at this higher dose, to observe early signs of activity, and to make a comparison to the 100 mg group for purposes of dose selection for the planned Phase IIb protocol. 

Overall Patients (Both Groups)

Changes in PSA levels were consistent with the properties of this class of agent. In most patients there is an initial increase followed by a decline and/or stabilization of the PSA levels. A decrease in PSA at any time after treatment is seen in 64% of the taxane-resistant evaluable patients with 25% greater than a 30% decline. Antitumor effects were noted in all doses studied including the lowest dose. In some individuals, there have been responses in bone scans ranging from decrease of tracer uptake to resolution of some bone lesions.

Harbor BioSciences has worked with the PCCTC and designed a 226 patient Phase IIb trial in both taxane-resistant and chemotherapy-naive CRPC patients, with doses that are based on the accumulated data.     

About Prostate Cancer

More than 1,000,000 men in the United States have prostate cancer; approximately 90,000 of these patients have late-stage prostate cancer, resulting in approximately 28,000 deaths each year. There are currently no approved treatments for end-stage (hormone and chemotherapy refractory) prostate cancer and the survival time is estimated to be between 8 and 12 months.

About Harbor BioSciences, Inc.     

Harbor BioSciences is a development-stage company with two product candidates in clinical trials: Apoptone in the cohort expansion portion of a Phase I/IIa trial of patients with late-stage prostate cancer, and Triolex® (HE3286), in a Phase IIa trial in obese type 2 diabetes mellitus patients.   Apoptone and Triolex represent the lead candidates from Harbor BioSciences' small molecule platform based on metabolites or synthetic analogs of endogenous steroid hormones. For more information on Harbor BioSciences please visit www.harborbiosciences.com.

⁽¹⁾ Kaplan-Meier Estimate is the standard statistical method for predicting the outcome of an ongoing study.

This press release contains forward-looking statements within the meaning of the federal securities laws concerning, among other things, the accrual of patients in our Phase I/IIa trial; dose escalation in our Phase I/IIa trial; Apoptone's inducement of cell death (apoptosis) in prostate tumors; Apoptone's potential as a complementary approach to interfere with androgen-receptor signaling to induce apoptosis in castrate-resistant prostate cancer; that responding patients in both the chemotherapy-experienced and chemotherapy-naive groups in our Phase I/IIa trial will continue to be offered treatment under the current protocol; toleration of our drug in our Phase I/IIa trial; and disease progression in our Phase I/IIa trial.   Any statement included in this press release that are not a description of historical facts are forward-looking statements that involve risks, uncertainties, assumptions and other factors which, if they do not materialize or prove correct, could cause Harbor BioSciences' actual results to differ materially from historical results or those expressed or implied by such forward-looking statements. Such statements are subject to certain risks and uncertainties inherent in the Company's business, including, but not limited to: the ability to complete preclinical and clinical trials successfully and within specified timelines, if at all; the Company's capital needs; the Company's ability to obtain additional funding; our ability to obtain regulatory approval for Apoptone, Triolex, or any other investigational drug candidate; and other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Except as required by law, Harbor BioSciences undertakes no obligation to update or revise the information contained in this press release as a result of new information, future events or circumstances arising after the date of this press release.