Data showing givinostat can be a safe and effective treatment for boys with Duchenne muscular dystrophy are raising hopes of new therapeutic avenues for the condition.

While there is still no silver bullet, the phase 3 trial highlights the potential of histone deacetylase inhibition – as provided by givinostat – as an additional component in Duchenne management, it is being argued.

The randomised, double-blind, placebo-controlled trial included 179 ambulant boys in 11 countries, all aged older than six years with genetically confirmed diagnoses and already on stable treatment with corticosteroids.

Findings showed a decline in four-stair climb assessment times after 72 weeks in both the 118 patients who received givinostat and the remainder who were given placebo treatment.

However, the decline was significantly smaller with givinostat (1.25 s) than with placebo (3.03 s), the researchers reported in The Lancet Neurology (link here).

Secondary outcomes were also superior in the active treatment arm, which averaged better scores in the functional North Star Ambulatory Assessment and other measures, such as a change in time to rise and six-minute walk, albeit without a statistically significant result.

But there were issues with drug tolerance, with the starting dose needing to be reduced following a masked interim safety review. Beyond that, some 48% of boys in the givinostat group required dose reduction, mainly due to adverse events, compared with 11% in the placebo group,

The most common adverse events in the givinostat group were diarrhoea (43 of 118 boys vs 11 of 61 receiving placebo) and vomiting (34 vs 8); no treatment-related deaths occurred.

But no new safety signals were reported by the team, which is now conducting an ongoing extension study evaluating long-term safety and efficacy.

Expert cautiously optimistic

Importantly, the observed treatment effects occurred in addition to the benefits derived from a stable glucocorticoid regimen, which was used in all patients, it was noted in a linked commentary (link here).

“The observed benefits of givinostat in this study suggest new therapeutic avenues for treating patients with Duchenne muscular dystrophy,” wrote Professor Janbernd Kirschner of the University of Freiburg Department of Neuropediatrics and Muscle Disorders.

“Recognising that no single treatment is likely to arrest the progression of the disease fully, a multifaceted therapeutic strategy might be needed in the future.”

“Alongside corticosteroids and treatments aimed at restoring dystrophin, histone deacetylase inhibition—as provided by givinostat—could be an additional component in the management of Duchenne muscular dystrophy, potentially reducing inflammation and fibrosis.”

Another positive was givinostat’s mode of action, which was not mutation-specific and could have potential to address similar downstream effects in other types of muscular dystrophy, said Professor Kirschner.

But whether it could engender clinically meaningful improvements in a wider cohort of Duchenne patients remained to be seen, he added.

He concluded: “Considering the mixed history of successes and setbacks in the development of treatment for this condition, managing expectations continues to be a major challenge in the daily care of patients and their families, underscoring the need for a balanced and informed approach.”