Givinostat in Duchenne muscular dystrophy: a profile of its use

Givinostat (Duvyzat™) is an efficacious and generally well-tolerated histone deacetylase (HDAC) inhibitor approved in the EU and the USA for the treatment of Duchenne muscular dystrophy (DMD) in patients aged ≥ 6 years. It is the first non-steroidal therapy available for the treatment of DMD arising from all genetic causes. By inhibiting HDACs, some of which are constitutively activated in DMD, givinostat initiates a cascade of events leading to improved muscle regeneration and reduced inflammation in dystrophin-deficient muscles. In the randomised, multinational phase 3 EPIDYS trial in ambulant boys with DMD receiving concomitant corticosteroid treatment, twice-daily oral givinostat significantly reduced four-stair climb worsening compared with placebo over 72 weeks. Additional functional outcomes favoured givinostat over placebo but did not reach statistical significance. The most common adverse events were thrombocytopenia, hypertriglyceridaemia and gastrointestinal disturbances; these were typically mild or moderate in severity and were generally manageable with dose reduction or interruption. The ongoing long-term safety extension has not identified any new safety signals. Duchenne muscular dystrophy (DMD) is a severe and progressive neuromuscular disease. An absence of dystrophin, a muscle cell-stabilising protein, leads to muscle damage and loss of function and, ultimately, early death. In DMD, continuous histone deacetylase (HDAC) activation contributes to disease progression. Givinostat (Duvyzat™), an oral HDAC inhibitor, is the first non-steroidal therapy for DMD caused by any genetic mutation and is approved in the EU and the USA in patients aged ≥ 6 years. In these patients, twice-daily givinostat in addition to corticosteroids resulted in significantly less decline in four-stair climb time (an assessment of motor function) than placebo in a 72-week clinical trial. Adverse events were generally mild or moderate in severity; no new safety concerns have been raised from a long-term extension study. Thus, givinostat, when added to corticosteroid treatment, is an efficacious and generally well-tolerated treatment for patients with DMD.