Triolex® Demonstrates Evidence of Anti-Inflammatory Activity in a Phase IIa Clinical Trial in a Subset of Type 2 Diabetes Mellitus Patients
San Diego, CA - May 10, 2010 - Harbor Biosciences (NASDAQ:HRBR), a biopharmaceutical company developing novel therapeutics for the treatment of cancer, metabolic and inflammatory diseases, today released an update to its development program for Triolex to treat obesity-induced insulin resistance and type-2 diabetes mellitus (T2DM).
Triolex is a synthetic derivative of a naturally occurring steroid in humans, which is currently in clinical development. Triolex has demonstrated potent anti-inflammatory properties in numerous animal models of inflammation, but without the side effects associated with the commonly used glucocorticoid anti-inflammatory steroid products. In a recently completed three-month Phase IIa clinical trial of patients with T2DM, those who were obese and were treated with Triolex showed significantly improved blood levels of hemoglobin A1c (HbA1c).
Recently Completed Phase II Study
The purpose of this double-blind, randomized, placebo controlled study was to assess the safety, tolerance and activity of Triolex administered orally for 12 weeks in patients with type 2 diabetes mellitus. The Phase IIa T2DM proof-of-principle trial was conducted in two stages: an exploratory phase in patients with diabetes whose disease was inadequately controlled while taking a stable dose of the diabetes drug metformin (treatment-experienced patients) and a subsequent confirmatory stage in patients not on metformin (treatment-naïve). The primary endpoint was to determine the difference in HbA1c levels (a marker of blood glucose) in Triolex-treated patients when compared to placebo.
While there was no significant HbA1c difference in the overall Triolex-treated patients when compared to placebo in either stage of the trial, subpopulations were found in both stages that responded to Triolex. In the second stage of the study, a retrospective analysis identified obese patients in the drug-naïve group (BMI = 31.3) that responded to treatment; a significant time-dependent decrease in HbA1c was observed with a change from baseline of -0.55% at day 84 and -1.1% at day 112 (p=0.041). Triolex reduced HbA1c at least 1.0 % in 5/9 (56 %) compared to 2/13 (15%) in the placebo group at day 112.
Fasting plasma glucose levels were decreased but the change from placebo did not reach statistical significance. However, measurement of the treatment effects on post-meal (post-prandial) glucose in both responding Phase II patient populations (Triolex vs placebo), using the 1, 5-anhydroglucitol biomarker (GlycoMark assay), demonstrated that Triolex significantly improved post-prandial glucose control (urinary 1, 5-anhydroglucitol reabsorption) on day 84 (+ 1.8 µg/mL, p=0.038) vs. placebo (- 0.1 µg/mL).
These results suggest that Triolex decreased obesity-induced inflammation and insulin resistance in type 2 diabetes patients. BMI at entry varied between the two stages of the study (BMI > 26.0 in stage 1 vs. BMI of > 31.3 in stage 2). The treatment-naïve patients in stage 2 with the higher BMI showed a more robust response to Triolex.
Jerrold M. Olefsky, M.D., Dean for Scientific Affairs and Professor of Medicine at the University of California San Diego School Of Medicine, commented: "Chronic tissue inflammation is emerging as a substantial cause of insulin resistance in obese patients with type 2 diabetes, so it is important to fully explore the potential of anti-inflammatory therapeutic approaches to this disease. Triolex produced excellent anti-inflammatory, insulin sensitizing effects in preclinical studies. The early clinical results in the more obese patients with elevated signs of inflammation show some promise and should be further explored."
Triolex was found to be safe and well tolerated in both treatment-naïve and metformin-treated T2DM patients; of the 4 SAE's reported in the 164 subjects, only 1 SAE, an elevated amylase, was reported as possibly related to study drug. Triolex has an estimated margin of safety greater than 80 based on plasma-drug exposure for the 10 mg dose used in this trial.
A study to identify the Triolex target organs in obese, impaired glucose-tolerant assessment of optimal combination effects with marketed products. This trial is designed to study Triolex effects on liver glucose output and muscle glucose uptake in response to insulin. Results from this study are expected in Q3 2010.
"We are encouraged by the activity that has been observed in the Triolex Phase IIa trials," stated James Frincke, Ph.D., President and Chief Executive Officer of Harbor BioSciences. "This data will be reviewed with potential corporate partners to determine the most favorable plan for further development of the drug in obesity-related metabolic diseases. Currently, approximately one third of Americans are obese (defined by a BMI > 30 kg/m2); and the potential to intervene in inflammatory-mediated metabolic processes with a safe, oral medication offers significant future promise for this condition."
Details of the Triolex technical analysis can be found on the Harbor BioSciences home page (www.harborbiosciences.com) in the "Triolex Clinical Development Backgrounder" under the Highlights section.
Previously, Triolex demonstrated potent anti-inflammatory properties in numerous animal models of inflammation. Triolex has been studied in the standard in vivo mouse models of insulin resistance and these results were recently published in the peer reviewed scientific literature. (Amelioration of glucose intolerance by the synthetic androstene HE3286: link to inflammatory pathways. Wang T, Villegas S, Huang Y, White SK, Ahlem C, Lu M, Olefsky JM, Reading C, Frincke JM, Alleva D, Flores-Riveros J. J Pharmacol Exp Ther. 2010 Apr;333(1):70-80).
The beneficial effects of Triolex on glucose homeostasis, liver cholesterol and triglyceride in the diabetic fatty Zucker rat have also been recently published. (A new antidiabetic compound attenuates inflammation and insulin resistance in Zucker diabetic fatty rats. Lu M, Patsouris D, Li P, Flores-Riveros J, Frincke JM, Watkins S, Schenk S, Olefsky JM., Am J Physiol Endocrinol Metab. 2010 May; 298(5)).
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 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.
This press release contains forward-looking statements within the meaning of the federal securities laws concerning, among other things, Triolex decreasing obesity-induced inflammation and insulin resistance in type 2 diabetes patients in the recently completed Phase IIa clinical trial of patients with T2DM; Triolex representing a new class of agents targeted to fat-induced insulin resistance; further studies to identify the optimal dose range in obese, pre-diabetic and diabetic patients; Triolex's margin of safety based on plasma-drug exposure for the 10 mg dose used in the recently completed Phase IIa clinical trial; timing of results from the study to identify the Triolex target organs in obese, impaired glucose-tolerant subjects; potential corporate partners reviewing data from the recently completed Phase IIa clinical trial; further development of Triolex in obesity-related metabolic diseases; and Triolex intervening in inflammatory-mediated metabolic processes. 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 risks that the development of Triolex may not proceed due to financial, technical, commercial or other reasons; that results to date with the Company's compounds may not be predictive of future clinical results; 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; the Company's 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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Source: Harbor BioSciences, Inc.