MK-2866 (Ostarine™)
GTx and its collaboration partner, Merck & Co., are evaluating Ostarine™ (also designated by Merck as MK-2866) and other selective androgen receptor modulators, or SARMs, for a variety of potential indications, including chronic sarcopenia, which is the loss of skeletal muscle mass resulting in reduced physical strength and ability to perform activities of daily living, muscle loss in patients with chronic obstructive pulmonary disease (COPD), and other musculoskeletal wasting conditions.
Chronic Sarcopenia
Chronic sarcopenia is a disease state of progressive skeletal muscle loss associated with impaired strength and mobility frequently accompanied by disability and a loss of independence. Chronic sarcopenia can exacerbate and be aggravated by comorbid illnesses, such as diabetes, depression and frailty in the elderly. There are currently no FDA approved therapies for chronic sarcopenia.
In December 2006, GTx completed a Phase II clinical trial evaluating four doses of Ostarine (0.1, 0.3, 1.0 and 3.0 mg) compared to placebo in 120 patients comprised equally of postmenopausal women and elderly men. The treatment period in the study was three months. In that trial, Ostarine treatment compared to placebo resulted in a dose-dependent increase in lean body mass and an improvement in muscle function (performance) in a 12 stair climb test measuring speed and calculating power. Ostarine had a favorable safety profile, with no serious adverse events reported. Ostarine also exhibited tissue selectivity with beneficial effects on lean body mass and performance and with no apparent change in measurements of serum PSA, sebum production or serum LH.
Cancer Cachexia
Cancer cachexia, or the unintentional loss of muscle mass and body weight, may lead to loss of protein stores, severe weakness and fatigue, immobility, loss of independence and an inability to tolerate and respond to cancer treatments. An estimated 1.3 million cancer patients in the United States have cancer cachexia.1 Cancer-induced muscle wasting is thought to be responsible for greater than 20% of cancer deaths.2
There are no drugs currently approved for the treatment of cancer wasting.
In October 2008, GTx announced topline results of the Phase II trial evaluating Ostarine in patients with cancer cachexia. The clinical trial enrolled 159 cancer patients (average age of 66 years) with non-small cell lung cancer, colorectal cancer, non-Hodgkin lymphoma, chronic lymphocytic leukemia or breast cancer at 35 sites in the U.S. and Argentina. Participants were randomized to receive placebo, 1 mg or 3 mg oral capsule of Ostarine once daily for 16 weeks. Average reported weight loss prior to entry among all subjects was 8.8%. Subjects were allowed to have standard chemotherapy during the trial.
The study met its primary endpoint of absolute change in total lean body mass (muscle) compared to placebo and the secondary endpoint of muscle function (performance). The incidence of serious adverse events, deaths and tumor progression were similar among placebo and the treatment arms. The most common side effects reported among all subjects in the trial were fatigue, anemia, nausea and diarrhea.
References
1. Tan HL and Fearon KC Curr Opin Clin Nutr Metab Care 2008, 11:400-7.
2. Tisdale MJ J Support Oncol 2003, 1:157-68.