updated 9/15/2010 8:45:41 AM ET 2010-09-15T12:45:41

SAN DIEGO, Sept. 14, 2010 (GLOBE NEWSWIRE) -- Harbor BioSciences, Inc. (Nasdaq:HRBR) a biopharmaceutical company developing novel therapeutics for the treatment of cancer, metabolic and inflammatory diseases, today released 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.

The most current results from this study include data on the 100 mg and 350 mg cohorts of chemotherapy-naive patients. One patient in the 350 mg group has a confirmed partial overall response of the disease. The median time to progression (TTP) for the 100 mg cohort is 24 weeks. The median TTP has not been reached for the 350 mg dose. 

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 remarked: "This is an exciting finding because, at the 350 mg dose, we are seeing a quantitative response by RECIST criteria. This response correlates with the patient having the highest serum levels seen thus far and without any evidence of toxicity.   Further dose escalation is justified to explore the promise of activity at higher serum concentrations of the drug."

Dose escalation to 700 mg has been initiated based on both the quantitative response and experience with the 350 mg dose, which demonstrate that the drug is safe and well tolerated.

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

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, 350 and 700 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.

Apoptone Phase I/IIa Clinical Study Update

Chemotherapy-Naive Patient Group

Twenty-two chemotherapy-naive patients were enrolled in two cohorts of eleven patients each, receiving either 100 mg or 350 mg of Apoptone per day. Ten patients of each cohort reached their first reassessment at eight weeks with stable disease and have received one to eight additional cycles of Apoptone. Three patients in the 100 mg group and eight patients in the 350 mg group remain on study. 

One patient in the 350 mg group has a confirmed partial overall response of the disease. The patient had a target tumor (by RECIST criteria) that was 1.1 centimeters in the longest diameter, which disappeared after 56 days. This response was confirmed with a repeat scan 8 weeks later. 

"The response in this patient was impressive and rapid and his bone scan remains stable," commented Michael Gordon, M.D., Oncologist and Associate Professor of Clinical Medicine at the University of Arizona College of Medicine.  "Other non-target tumors that do not qualify by RECIST criteria at baseline also decreased in size, indicating the response to the soft tissue was more widespread than to the one target tumor.  I expect continued regression of tumor in the upcoming radiographic assessments.  Apoptone continues to show a good safety profile and is well tolerated at these higher doses," Dr. Gordon added.

 Taxane-Resistant Patient Group

A total of 42 taxane-resistant prostate cancer patients with progressive (metastatic) disease were enrolled into the clinical trial at 7 dose levels. As previously reported, 28 (67%) reached the first reassessment (two 28-day cycles); 15 (54%) 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. 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 was well tolerated at all doses with no overt dose-limiting toxicities observed. 

The Kaplan-Meier estimate (1) for the median time to progression in evaluable taxane-resistant patients was 16 weeks (range 8-24) in this 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 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," explained 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 19 of the 42 patients may have been prematurely removed from the study without confirmation of disease progression, as required by the PCWG2 recommendations."

Overall Patients (Both Groups)

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 tumors.

About RECIST 1.1 Criteria

A target tumor is defined as a solid tumor with a minimum 1 centimeter (in the longest diameter) that has been designated at baseline as a target. Up to five target tumors can be identified and must be representative of the various organs in the body with solid tumors present with a maximum of two lesions per organ.

A partial response of a target tumor is a reduction in the diameter of 30% or greater from baseline and confirmed by repeat scans no less than 4 weeks later.   A complete target tumor response is the disappearance of the tumor and confirmed by repeat scans no less than 4 weeks later.

A partial overall response is defined as the disappearance of a target tumor with remaining target or non-target tumors. A complete overall response is the disappearance of all tumors.

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, dose escalation in our Phase I/IIa trial; Apoptone's inducement of cell death (apoptosis) in prostate tumors; the breath of the soft tissue response; the continued tumor regression in the patient who experienced a partial overall response; tolerability of our drug in our Phase I/IIa trial; and the underestimation of the TTP in the taxane-resistant patients.   Any statements 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.

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