Research in context
Evidence before this study
Age-associated muscle weakness is responsible for several poor outcomes in older people, including mobility disability, fall-related injuries, institutionalisation, and death. The standard of care for low muscle strength or power relies on resistance exercise training, but its efficacy is variable and its implementation often challenging in older disabled people. A drug that increases muscle power could prevent these poor outcomes. We searched PubMed up to April 1, 2015, with the search terms “clinical” and “trial” and [myostatin or activin] for clinical trials testing drugs that target myostatin or its receptor (AcRIIb) with no language restrictions. Although several molecules have been reported that increase muscle mass or its surrogate, lean mass, the data available about physical performance are limited. Positive effects were reported on 6 min walking distance with bimagrumab (AcRIIb antibody) in 11 patients with sporadic inclusion body myositis versus three patients given placebo, and with follistatin (natural myostatin inhibitor) gene therapy in six patients with Becker muscular dystrophy in an open-label clinical trial. Apart from the design and size limitations of these previous trials, it was unknown whether effects recorded in a purely muscular disorder (such as sporadic inclusion body myositis or Becker muscular dystrophy) would translate into older fallers whose impaired physical performance is generally multifactorial.
Added value of this study
We did a clinical trial testing an antimyostatin antibody in 201 older fallers with low muscle strength. In addition to achieving the primary endpoint (increase in appendicular lean mass), this antibody showed efficacy on several measures of physical performance, predominantly those that are heavily dependent on muscle power (consistent with the mechanism of action) and that are functional (eg, climbing stairs). This trial provides the first robust demonstration that inhibiting myostatin increases lean mass in older weak fallers and most importantly that these changes in lean mass translate into an improved physical performance which is what matters to these patients.
Implications of all the available evidence
Although the clinical importance of these improvements and this antibody's safety remain to be formally shown in larger confirmatory trials, LY might provide significant benefits to this high-risk older population, both in terms of quality of life and prevention of adverse outcomes such as fall related injuries or mobility disability.