吉维诺司他的适应症

Givinostat is a novel histone deacetylase (HDAC) inhibitor that has shown unique value in the treatment of specific neuromuscular diseases. This article will analyze the clinical application scope of this drug from three aspects: drug indications, pharmacological mechanism of action, and contraindications for use.

Indications of givenostat

The clinical application has a clear disease spectrum limitation, mainly targeting specific types of hereditary muscular dystrophy.

Duchenne Muscular Dystrophy (DMD)

Givenostat’s only approved indication is the treatment of Duchenne muscular dystrophy in patients 6 years of age and older. Clinical studies have confirmed that the drug can delay disease progression and improve patients' motor function. Suitable for patients who are able to walk independently or who require assisted walking.

Other potential indications

Research in the clinical trial phase shows that givenostat may have certain efficacy in Becker muscular dystrophy (BMD). In addition, a trend toward improved muscle function was observed in a phase II study in facioscapulohumeral muscular dystrophy (FSHD), but formal approval has not yet been obtained.

Applicable population characteristics

The ideal drug targets are patients diagnosed with DMD and retaining some ability to walk. Genetic testing to confirm dystrophin gene mutations is necessary for diagnosis. The patient's baseline platelet count needs to be ≥150×10⁹/L, and the triacylglycerol level should be within the normal range.

Accurately grasping the scope of indications is the first condition to ensure the rational use of givenostat.

Efficacy and effects of givenostat

Givinostat produces multiple therapeutic effects through a unique pharmacological mechanism, and its effects are different from traditional treatment options.

Disease-modifying effect

As an HDAC inhibitor, givenostat can regulate the expression of genes related to muscle regeneration. Clinical data shows that continuous treatment for 72 weeks can delay the patient's level 4 ladder climbing time and improve the 10-meter walking test. This protective effect on motor function increases with the extension of the treatment course.

Anti-inflammation and anti-fibrosis

The drug reduces muscle inflammatory response by inhibiting the NF-κB pathway. Muscle biopsy confirmed that muscle fiber necrosis was reduced and the degree of fibrosis was significantly reduced in the treatment group. Serum creatine kinase levels decreased, suggesting a sarcolemmal stabilizing effect of the drug.

Long-term functional protection

Extended studies show that patients who continue to receive treatment for 3 years will delay the time of wheelchair dependence by 18 months. The annual decline in lung function is slowed. This protective effect is particularly evident in patients aged 7-13 years, and long-term follow-up data support its potential to change the natural course of the disease.

Givenostat’s multiple pharmacological effects provide DMD patients with treatment options beyond symptom control.

Contraindications of givenostat

Clear medication contraindications are of great significance to prevent serious adverse reactions and need to be strictly evaluated before treatment.

Absolute contraindications

It is prohibited to be used by patients with platelet count <150×10⁹/L. Contraindicated for those known to be allergic to drug ingredients. This drug is contraindicated in patients with severe hepatic insufficiency (Child-Pugh class C). Patients with congenital long QT syndrome are listed as contraindications.

Relative contraindications

Patients with moderate hepatic insufficiency need to reduce the dosage. Use with caution in patients taking strong CYP3A4 inhibitors or inducers. Patients at risk for active gastrointestinal bleeding need to carefully evaluate the benefit-risk ratio.

Special contraindications

Contraindicated for pregnant women. Women of childbearing age must take reliable contraceptive measures. Breastfeeding women should suspend breastfeeding. Safety data for use in children under 6 years of age have not been established and use is not recommended.

Patients should read the instructions carefully before taking the medicine and follow the instructions of the doctor or pharmacist to avoid misuse, which may lead to reduced efficacy or increased side effects.