Givinostat, sold under the brand name Duvyzat is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used for the treatment of

Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy predominantly affecting boys. The onset of muscle weakness typically begins around age four, with rapid progression. Initially, muscle loss occurs in the thighs and pe ...

. It is a

histone deacetylase inhibitor Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that enzyme inhibitor, inhibit histone deacetylases. Since acetylation of histones, deacetylation of histones produces transcriptionally silenced heterochromatin ...

with potential

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

anti-angiogenic An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical d ...

, and antineoplastic activities. It is a histone deacetylase (HDAC) inhibitor that works by targeting pathogenic processes to reduce inflammation and loss of muscle. 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. Givinostat was approved for medical use in the United States in March 2024. Givinostat is the first

nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents. List of nonsteroidal steroid receptor mo ...

medication approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) to treat people with all genetic variants of Duchenne muscular dystrophy. The FDA considers it to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

Medical uses

Givinostat is indicated for the treatment of Duchenne muscular dystrophy in people six years of age and older.

Adverse effects

In clinical trials of givinostat as a

salvage therapy Salvage therapy, also known as rescue therapy, is a form of therapy given after an ailment does not respond to standard therapy. The most common diseases that require salvage therapy are HIV and various cancers. The term is not clearly defined; i ...

for advanced

Hodgkin's lymphoma Hodgkin lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the lymph nodes. The condition was named a ...

, the most common adverse reactions were

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

(seen in 50% of participants), mild

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

or abdominal pain (40% of participants), moderate

thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...

(decreased

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

counts, seen in one third of patients), and mild

leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...

(a decrease in

white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

levels, seen in 30% of patients). One-fifth of patients experienced

prolongation In music theory, prolongation is the process in tonality, tonal music through which a pitch (music), pitch, interval (music), interval, or triad (music), consonant triad is considered to govern spans of music when not physically sounding. It is a ...

of the

QT interval The QT interval is a measurement made on an Electrocardiography, electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the QRS complex, Q wave to the end of the T wave, an ...

, a measure of electrical conduction in the heart, severe enough to warrant temporary suspension of treatment.

Mechanism of action

Givinostat inhibits class I and class II

histone deacetylase Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important becaus ...

s (HDACs) and several pro-inflammatory

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s. This reduces expression of

tumour necrosis factor Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors ...

(TNF),

interleukin 1 The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults. Discovery Discovery of these cytokines began with studies on t ...

α and β, and

interleukin 6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...

. It also has activity against cells expressing ''JAK2(V617F)'', a mutated form of the

janus kinase 2 Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CS ...

(JAK2) enzyme that is implicated in the

pathophysiology Pathophysiology (or physiopathology) is a branch of study, at the intersection of pathology and physiology, concerning disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is ...

of many

myeloproliferative disease Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. ''Myelo'' refers to the bone marrow, ''proliferative'' describes the rapid grow ...

s, including polycythaemia vera. In patients with polycythaemia, the reduction of mutant JAK2 concentrations by givinostat is believed to slow down the abnormal growth of

erythrocyte Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...

s and ameliorate the symptoms of the disease.

History

ITF2357 was discovered at Italfarmaco of Milan, Italy. It was patented in 1997 and first described in the scientific literature in 2005. 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. The primary endpoint was the change from baseline to month 18 using a four stair climb to measure muscle function. 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. 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. 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. Compared to placebo, participants treated with givinostat saw less worsening in their NSAA score after 18 months. The US

(FDA) granted the application for givinostat

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

, fast track,

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

, and rare pediatric disease designations. The FDA granted the approval of Duvyzat to Italfarmaco S.p.A. The FDA approved givinostat based on evidence from a single clinical trial (NCT02851797) 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. The trial was conducted at 45 sites in 11 countries in North America and Europe. Twenty-eight of the participants were from the United States.

Society and culture

Legal status

In April 2025, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Duvyzat, intended for the treatment of Duchenne muscular dystrophy (DMD). The applicant for this medicinal product is Italfarmaco S.p.A. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The CHMP's opinion is based on data from a subgroup of 120 participants (79 treated with givinostat and 41 with placebo) in a randomized, placebo-controlled study in ambulant participants with Duchenne muscular dystrophy aged six years of age or older on concomitant steroid treatment. The safety profile of Duvyzat is based on data from 179 participants. The most common events in participants treated with givinostat were diarrhoea, abdominal pain, thrombocytopenia (low levels of blood platelets), vomiting, hypertriglyceridaemia (high blood levels of triglycerides, a type of fat) and fever. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Givinostat was authorized for medical use in the European Union in June 2025.

Names

Givinostat is the international nonproprietary name.

Research

Givinostat is in numerous phase II clinical trials (including for relapsed leukemias and myelomas), and has been granted

designation in the European Union for the treatment of systemic juvenile idiopathic arthritis, polycythaemia vera. and

. A preclinical study produced early results suggesting the molecule might help with diastolic dysfunction.