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Clinical data | |
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Trade names | Duvyzat |
AHFS/Drugs.com | Monograph |
MedlinePlus | a624025 |
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Routes of administration | By mouth |
Drug class | Histone deacetylase inhibitor |
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ECHA InfoCard | 100.258.524![]() |
Chemical and physical data | |
Formula | C24H27N3O4 |
Molar mass | 421.497 g·mol−1 |
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Givinostat, sold under the brand nameDuvyzat is amedication used for the treatment ofDuchenne muscular dystrophy.[1][2] It is ahistone deacetylase inhibitor with potentialanti-inflammatory,anti-angiogenic, andantineoplastic activities.[3] It is a histone deacetylase (HDAC) inhibitor that works by targeting pathogenic processes to reduce inflammation and loss of muscle.[2]
The most common side effects include diarrhea, abdominal pain, low platelets (thrombocytopenia), nausea/vomiting, an increase in triglycerides (a type of fat in the body) (hypertriglyceridemia), and fever.[2][4]
Givinostat was approved for medical use in the United States in March 2024.[2][5] Givinostat is the firstnonsteroidal medication approved by the USFood and Drug Administration (FDA) to treat people with all genetic variants of Duchenne muscular dystrophy.[2] The FDA considers it to be afirst-in-class medication.[6]
Givinostat is indicated for the treatment of Duchenne muscular dystrophy in people six years of age and older.[1][2]
In clinical trials of givinostat as asalvage therapy for advancedHodgkin's lymphoma, the most commonadverse reactions werefatigue (seen in 50% of participants), milddiarrhea or abdominal pain (40% of participants), moderatethrombocytopenia (decreasedplatelet counts, seen in one third of patients), and mildleukopenia (a decrease inwhite blood cell levels, seen in 30% of patients). One-fifth of patients experiencedprolongation of theQT interval, a measure of electrical conduction in the heart, severe enough to warrant temporary suspension of treatment.[7]
Givinostat inhibits class I and class IIhistone deacetylases (HDACs) and several pro-inflammatorycytokines. This reduces expression oftumour necrosis factor (TNF),interleukin 1α and β, andinterleukin 6.[8]
It also has activity against cells expressingJAK2(V617F), a mutated form of thejanus kinase 2 (JAK2) enzyme that is implicated in thepathophysiology of manymyeloproliferative diseases, including polycythaemia vera.[9][10] In patients with polycythaemia, the reduction of mutant JAK2 concentrations by givinostat is believed to slow down the abnormal growth oferythrocytes and ameliorate the symptoms of the disease.[11]
ITF2357 was discovered atItalfarmaco of Milan, Italy. It was patented in 1997 and first described in the scientific literature in 2005.[12][8]
The efficacy of givinostat for the treatment of Duchenne muscular dystrophy was evaluated in a randomized, double-blind, placebo-controlled 18-month phase III study.[2] The primary endpoint was the change from baseline to month 18 using a four stair climb to measure muscle function.[2] All participants continued to receive a standard of care steroid regimen throughout the study and, after 18 months of treatment, participants treated with givinostat showed statistically significant less decline in the time it took to climb four stairs compared to placebo.[2] The mean change from baseline to month 18 in time to climb four stairs was 1.25 seconds for participants receiving givinostat compared to 3.03 seconds for participants receiving placebo.[2] A secondary efficacy endpoint was the change from baseline to month 18 in physical function as assessed by the North Star Ambulatory Assessment (NSAA)—a scale commonly used to rate the motor function in boys with Duchenne muscular dystrophy who are capable of walking.[2] Compared to placebo, participants treated with givinostat saw less worsening in their NSAA score after 18 months.[2] The USFood and Drug Administration (FDA) granted the application for givinostatpriority review,fast track,orphan drug, and rare pediatric disease designations.[2] The FDA granted the approval of Duvyzat to Italfarmaco S.p.A.[2] The FDA approved givinostat based on evidence from a single clinical trial (NCT02851797[13]) of 179 males with Duchenne muscular dystrophy who were six years of age and older who could walk and were on stable background therapy with steroids.[1][4] The trial was conducted at 45 sites in 11 countries in North America and Europe.[4] Twenty-eight of the participants were from the United States.[4]
Givinostat is theinternational nonproprietary name.[14]
Givinostat is in numerous phase II clinical trials (including for relapsed leukemias and myelomas),[15] and has been grantedorphan drug designation in the European Union for the treatment ofsystemic juvenile idiopathic arthritis,[16]polycythaemia vera.[11] andDuchenne muscular dystrophy.
A preclinical study produced early results suggesting the molecule might help with diastolic dysfunction.[17]