Considerations in the development of drugs to treat sarcopenia.

Sarcopenia describes reduced skeletal muscle mass and impaired muscle function associated with aging and with a variety of chronic diseases prevalent in the aging population. With increasing understanding of the molecular pathways participating in the structural and functional changes affecting skeletal muscle in these conditions, a number of potential targets for pharmacological interventions to reverse sarcopenia have been identified. The clinical evaluation of therapeutic candidates directed at these targets will require that the efficacy and safety of the drug candidates be adequately evaluated to meet the regulatory standards of the Food and Drug Administration (FDA). Concerns unique to drug development may require different approaches to clinical study design than have been used in the epidemiological research that identified the clinical need for these programs and the intervention trials conducted to date. In addition to being responsive to clinical need as perceived by patients and physicians, clinical trial data must demonstrate to the FDA that the drug provides an objective and clinically meaningful advantage, and must demonstrate to all involved in healthcare decision-making that its benefits justify the associated costs and risks. Potential primary efficacy endpoints for trials of a drug for treatment of sarcopenia include physical performance, falls, fractures, and patient-reported outcomes assessing function and quality of life. Each potential endpoint has advantages and disadvantages from scientific, clinical, and regulatory perspectives that must be carefully considered in the design of trials for sarcopenia treatments.