Duvyzat (givinostat) is the first non-steroidal drug approved by the US FDA for all genetic variant types of Duchenne muscular dystrophy (DMD). The drug slows disease progression by targeting the activity of histone deacetylase (HDAC), providing a new treatment option for DMD patients aged 6 years and above.
Instructions for Duvyzat (givinostat) for the treatment of Duchenne muscular dystrophy
Applicable population and FDA approval background
Duvyzat is suitable for male patients aged 6 years and above who have been genetically diagnosed with DMD. On March 21, 2024, the drug received accelerated approval from the FDA based on key clinical trials showing that it can significantly improve muscle function scores (MFM-32 scale). The original drug produced by Italfarmaco S.p.A. in Spain has a specification of 140ml.
Treatment goals and coverage
Duvyzat is the eighth approved DMD therapy in the world and the only drug that covers all types of gene mutations. Its indications are not limited to patients with specific exon deletions, and provide treatment possibilities for rare mutation types (such as point mutations and repeated mutations).
Clearly defining the scope of indications will help patients and their families develop personalized treatment plans. The following content will analyze the core mechanism of action and clinical effects of Duvyzat.
Effects of Duvyzat
Duvyzat improves muscle degeneration and functional loss in DMD patients by inhibiting histone deacetylase (HDAC) activity, regulating gene expression and inflammatory response. Clinical data show that it can delay disease progression and improve patients' quality of life.
HDAC inhibition and muscle protection
HDAC overactivation can lead to muscle regeneration disorders and fibrosis. Duvyzat selectively inhibits HDAC6/8, restores muscle stem cell differentiation ability, and reduces abnormal collagen deposition. 48 weeks of treatment can reduce creatine kinase (CK) levels by about 30%, indicating reduced muscle damage.
Functional improvement and clinical data
In the Phase III clinical trial, patients treated with Duvyzat had a 40% slower rate of decline in MFM-32 scores, and maintained a 6-minute walking distance of 15 meters more than the placebo group. The daily oral dose for patients weighing ≥40kg is 44.3mg (corresponding to 5ml suspension), which needs to be taken with meals to improve bioavailability.
Understanding the mechanism of action of the drug can enhance patients' confidence in treatment. The following content will explain the common and serious adverse reactions management strategy of Duvyzat.
Side effects of Duvyzat
Duvyzat treatment may cause blood system abnormalities, gastrointestinal symptoms and cardiac risks. Timely identification and intervention can reduce the rate of treatment interruption and ensure the safety of medication.
Management of thrombocytopenia and diarrhea
About 35% of patients have a decrease in platelet count, and the complete blood count needs to be tested monthly. If the platelet count is <150×10⁹/L, the dose needs to be reduced stepwise according to weight (such as 60kg patients from 53.2mg to 39.9mg). 37% of patients have diarrhea, and moderate and severe cases need to suspend medication and supplement electrolytes.
Cardiac monitoring and dose adjustment
The incidence of QTc interval prolongation is 5%, and the risk is increased in patients with abnormal baseline electrocardiogram or taking other QT-prolonging drugs. Electrocardiograms need to be tested every 3 months during treatment. If QTc>500ms or increases by>60ms from baseline, the drug should be discontinued immediately. When serum triglycerides are >300mg/dL, combined lipid-lowering drug intervention is required.
Strictly following the blood and heart monitoring plan is the key to ensuring the continuity of treatment. Patients should seek medical attention immediately if they experience subcutaneous ecchymosis, palpitations, or persistent diarrhea. The drug must be used within 60 days after opening, and the storage temperature must be controlled at 15°C-30°C. Through standardized medication and regular follow-up visits, Duvyzat is expected to bring DMD patients a longer functional maintenance period.
