Selective Androgen Receptor Modulator (SARM)

LGD-4033 is a non-steroidal selective androgen receptor modulator (SARM), expected to produce the therapeutic benefits of testosterone with improved safety, tolerability and patient acceptance due to tissue-selective mechanism of action and an oral route of administration.

Ligand has discovered several novel orally active, non-steroidal SARM compounds, including LGD-4033, based on tissue-specific gene expression and other functional, cell-based technologies. In animal models, LGD-4033 demonstrates anabolic activity in muscles, anti-resorptive and anabolic activity in bones and a robust selectivity for muscle and bone versus prostate and sebaceous glands. LGD-4033 has recently completed a Phase I Multiple Ascending Dose study in healthy volunteers.

Goals of SARM Therapy:

 Improve Lean Body Mass (LBM)
 Improve muscle strength
 Improve Physical Performance
 Enhance Quality of Life(QOL)

LGD-4033 has the potential to prevent and treat a variety of muscle wasting conditions:

 

Clinical Experience

Phase I single and multiple dose escalation studies of LGD-4033 were conducted in a total of 116 healthy male subjects. The safety, tolerability and preliminary efficacy of LGD-4033 was evaluated in the double-blind, placebo-controlled Phase I multiple ascending dose study. Healthy male subjects were randomized to receive 0.1, 0.3 or 1.0 mg LGD-4033 or placebo once daily over 21 days.

Key findings of this study include:

 LGD-4033 was safe and well tolerated at all doses following daily oral administration for three weeks in young healthy males 
 No clinically significant dose-related adverse events were reported 
 No clinically significant changes in liver function tests, PSA, hematocrit or ECG were seen 
 Positive dose-dependent trends in lean muscle mass increase were observed with drug-treated subjects 
 Positive dose-dependent trends in functional exercise and strength measures were consistent with anabolic activity

LGD-4033 is positioned to enter into Phase II development. Studies are planned to evaluate LGD-4033 over 12-weeks of oral dosing in conditions such as muscle wasting associated with cancer, acute rehabilitation (e.g. hip fracture), and acute illness.
Cachexia is a wasting syndrome defined by progressive weight loss, anorexia, and muscle atrophy. Cachexia is a significant factor in the poor performance status and high mortality rate of patients in multiple disease states such as cancer, COPD, severe burns, AIDS and end stage renal disease. Cachexia significantly impairs quality of life and response to medical treatment. Approximately 25% of all cancer deaths can be attributed to cachexia.

SARM Posters and Presentations

 Phase I clinical trial of LGD-4033, a novel selective androgen receptor modulator (SARM)
 LGD-4033 builds muscle and bone with reduced prostate activity and may be beneficial in age-related frailty 
 LGD-4033, a Novel Non-Steroidal Oral Selective Androgen Receptor Modulator (SARM), is Safe in Healthy Young Men
 The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men