The European Medicines Agency (EMA) has recommended granting conditional marketing authorisation for Duvyzat® (givinostat) to treat Duchenne muscular dystrophy (DMD) in ambulant patients aged six years and older. If approved by the European Commission, Duvyzat will become available across the European Union as an oral therapy taken alongside corticosteroids.

Duchenne muscular dystrophy is a devastating, progressive genetic disorder caused by mutations in the DMD gene, leading to the absence of dystrophin—a critical protein that maintains muscle fibre strength and integrity. Without dystrophin, muscles progressively weaken, leading to loss of ambulation and eventually affecting the heart and respiratory system.

Current treatments, centred around corticosteroids and supportive care, offer limited options. Duvyzat represents a novel approach by targeting histone deacetylase (HDAC) activity, which is abnormally high in DMD muscles and contributes to inflammation and tissue scarring.

Clinical Evidence Behind the Recommendation

The EMA’s positive opinion is based on the Phase 3 EPIDYS trial, a randomized, placebo-controlled study involving 179 ambulant boys aged six and older, all receiving corticosteroid therapy.

• Primary Endpoint: Duvyzat significantly delayed motor decline, showing a smaller increase in time needed to climb four stairs (4SC test) compared to placebo (1.25 seconds vs. 3.03 seconds).

• Secondary Endpoints: Duvyzat demonstrated favourable results in measures of muscle strength and structure, including the North Star Ambulatory Assessment (NSAA) and MRI analysis of fat infiltration.

While some secondary endpoints did not reach statistical significance individually, they consistently favoured Duvyzat, suggesting an overall trend toward preserving muscle function.

Duvyzat’s safety profile was acceptable, with most adverse events such as diarrhoea, thrombocytopenia, and fever being mild to moderate.

Regulatory Status and Future Steps

Duvyzat had already gained approval in the United States and the United Kingdom in 2024.

• In the US, it was approved for all DMD patients aged six and above, regardless of ambulation.

• In the UK, it received full approval for ambulant patients and conditional approval for non-ambulant patients.

Pending final approval from the European Commission, expected by July 2025, Italfarmaco will work closely with European Member States to make Duvyzat accessible as quickly as possible.

As part of the conditional approval pathway, Italfarmaco has committed to further clinical studies, including trials in younger (2–5 years) and non-ambulant DMD patients.

Cosmael ThinkLab Commentary

The development and pending European approval of Duvyzat mark an important milestone for patients with Duchenne muscular dystrophy. Its novel mechanism—modulating HDAC activity rather than targeting dystrophin directly—represents a broader therapeutic strategy that could benefit many genetic variants of DMD.

While conditional approval highlights the need for continued evidence generation, the early access to a potentially disease-modifying treatment is a major step forward. Duvyzat’s success could also inspire the exploration of HDAC modulation in other neuromuscular and rare diseases.

Sources:

• Italfarmaco S.p.A. Press Release, April 2025

• European Medicines Agency (EMA) CHMP Opinion, April 2025