Duvyzat (givinostat) / Italfarmaco, Medis, Multicare Pharmaceuticals - LARVOL DELTA

Understanding Pharmacokinetic-Drug Interactions With Drugs Approved by the US Food and Drug Administration in 2024 to Better Manage the Risk of Drug Interactions With Concomitant Medications: A Review of Clinical Data From New Drug Applications. (PubMed, Curr Ther Res Clin Exp) - "Of these, 7 drugs were substrates of CYP3A, 3 of CYP2C9, one of CYP1A2, and one of CYP2C8, including the sensitive substrates vanzacaftor (CYP3A) and vorasidenib (CYP1A2). As precipitants, 6 drugs (acoramidis, cefepime/enmetazobactam, givinostat, lazertinib, mavorixafor, and resmetirom) were clinical inhibitors of CYP enzymes (2C8, 2C9, 2D6, 2E1, and 3A), with mavorixafor being a CYP2D6 strong inhibitor. Two drugs (elafibranor and tovorafenib) showed weak induction of CYP3A. Regarding transporter data, 3 drugs were substrates of transporters, including seladelpar (BCRP and OAT3), sulopenem (OAT3), and vadadustat (OAT1/3), and 8 drugs (arimoclomol, danicopan, givinostat, lazertinib, mavorixafor, resmetirom, vadadustat, and vazacaftor/tezacaftor/deutivacaftor) were inhibitors of transporters...Several DDIs with an AUC change <2 also had labeling recommendations, pertaining most often to the concomitant use of drugs with a narrow therapeutic index. Mechanistic DDI..."

Clinical data • FDA event • Journal • NDA • PK/PD data • Review • CYP1A2 • CYP2C9

The Diverse Effect of HDAC Inhibitors: Sodium Butyrate and Givinostat on Microglia Polarization After Hypoxia-Ischemia In Vitro. (PubMed, Int J Mol Sci) - "This effect is associated with suppression of pro-inflammatory gene expression and activation of the PI3K/AKT signaling pathway. These results identify sodium butyrate as a potential modulator of microglial responses following ischemic injury."

Journal • Preclinical • Cardiovascular • Inflammation • CD86 • IL1B • TNFA

Givinostat in Duchenne's Muscular Dystrophy Long-term Safety and Tolerability Study (clinicaltrials.gov) - P2/3 | N=206 | Recruiting | Sponsor: Italfarmaco | Active, not recruiting ➔ Recruiting

Enrollment open • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Pharmacokinetics, Safety and Tolerability of ITF2357 in Participants With Chronic Hepatic Impairment and With Normal Hepatic Function (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Italfarmaco | Recruiting ➔ Completed

Trial completion • Hepatology

Targeting autophagy in Duchenne muscular dystrophy: mechanistic insights and emerging therapeutic strategies. (PubMed, J Med Genet) - "Recent preclinical studies highlight the therapeutic potential of pharmacological and dietary autophagy modulators, including rapamycin, 5-aminoimidazole-4-carboxamide ribonucleotide, low protein diets, SRT2104 and Givinostat, which improve autophagic flux, restore mitochondrial integrity and attenuate fibrosis. Lifestyle interventions and combinatorial approaches further underscore the importance of integrating multimodal strategies.Further research should focus on longitudinal studies to optimise therapeutic timing, validate dynamic biomarkers (LC-II, p62, miRNAs) and leverage artificial intelligence with multiomics integration for precision therapies. Targeting autophagy and its interconnected pathways holds promise for transforming DMD management and improving patient outcomes."

Journal • Review • CNS Disorders • Duchenne Muscular Dystrophy • Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Metabolic Disorders • Muscular Atrophy • Muscular Dystrophy • Musculoskeletal Diseases • Myositis • Respiratory Diseases

Duchenne UK is proud to welcome a major breakthrough for families affected by Duchenne muscular dystrophy (DMD) in Scotland, as the Scottish Medicines Consortium (SMC) approves a new treatment for use on the NHS in Scotland. (Duchenne UK) - "Our Project HERCULES built critical evidence on the real-world impact of DMD, which was used in our submission to the SMC to help demonstrate the potential quality of life benefits of the medicine...Givinostat remains under review by the National Institute for Health and Care Excellence (NICE) for use in NHS England and guidance is yet to be issued."

Reimbursement • Duchenne Muscular Dystrophy

Corticosteroid treatment in Duchenne muscular dystrophy. (PubMed, Arch Pediatr) - "Corticoids are started and maintained at the theoretical dose of 0.75 mg/kg/day of prednisone/prednisolone or 0.9 mg/kg/day of deflazacort, adjusting the dose to weight if the benefit-risk ratio favors treatment. The only reasons to discontinue treatment when the patient and family are adhering to it are the uncontrolled side effects. Thus, in many countries including France, as of late 2025, the only routinely prescribed symptomatic treatment for DMD remains conventional corticosteroids, which will be discussed in this article, followed by a description of vamorolone, a dissociative steroidal compound, and givinostat, a histone deacetylase inhibitor."

Journal • Review • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Genetic Disorders • Infectious Disease • Muscular Dystrophy • Obesity • Osteoporosis • Respiratory Diseases • Rheumatology

Trial in progress: Efficacy and safety of givinostat versus hydroxyurea in patients with polycythemia vera (GIV-IN-PV) (ASH 2025) - P3 | "Current treatments include aspirin,phlebotomies, and cytoreductive drugs, most commonly hydroxyurea (HU) (Tefferi A, Am J Hematol.2023; 98:1465-1487). As of June 2025, 95 patients havebeen randomized in 76 investigational sites worldwide. Countries open for recruitment include Austria,Bulgaria, Croatia, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, Poland, Serbia, Spain,Turkey, UK, US."

Clinical • Hematological Malignancies • Leukemia • Myelofibrosis • Polycythemia Vera • Thrombosis • ABL1 • BCR

Using a medically trained LLM-based end-to-end system in automating patient eligibility screening across a health system for A phase 3 study evaluating the safety of givinostat in patients with polycythemia vera. (ASH 2025) - P3 | "LLMs embedded within EHRs can transform the efficiencyand scope of trial recruitment.We evaluated Synapsis AI, a medically trained, large language model-based (LLM-based) end-to-endsystem, focusing on its accuracy and efficiency in identifying eligible patients for an active PV clinical trial,being conducted at Cleveland Clinic. The trial is a randomized, phase 3 study comparing givinostat versus hydroxyurea(NCT06093672). This comparison demonstrates the potential of a medically trained LLM-based system foraccelerating and expanding patient identification and recruitment for clinical trials, significantly reducingthe time and effort required. The stark contrast in the number of patients identified highlights thesignificant efficiency and time-saving advantage of Synapsis AI's automated pre-screening overconventional screening methods. By streamlining the recruitment process, tools like Synapsis AI canenhance trial efficiency and support faster development of..."

Clinical • P3 data • Hematological Malignancies • Polycythemia Vera • Rare Diseases

Comparative Study of Histone Deacetylase Inhibitors for Radiation Protection Using Survival Outcomes in a Mouse Model. (PubMed, Biol Pharm Bull) - "Male ICR mice received 7.5 Gy TBI followed by a single administration of valproic acid (VPA; 300 or 600 mg/kg), sodium butyrate (NaB; 500 or 1000 mg/kg), trichostatin A (TSA; 0.5 or 1.0 mg/kg), vorinostat (10 or 50 mg/kg), panobinostat (25 or 50 mg/kg), givinostat (5 or 10 mg/kg), or entinostat (25 or 50 mg/kg). VPA's efficacy may reflect a combination of effects on DNA repair, inflammation, and redox regulation rather than HDAC inhibition alone. These findings suggest VPA to be a promising candidate for radioprotection and emphasize the need for further studies to optimize dosing and explore underlying mechanisms."

Clinical • Journal • Preclinical • Inflammation

Trial in Progress: Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera (GIV-IN-PV) (MPN 2025) - No abstract available

Clinical • Polycythemia Vera

Exploring Quality of Life in Duchenne Muscular Dystrophy: Insights From Qualitative Patient and Caregiver Interviews (ISPOR-EU 2025) - "This study aims to generate comprehensive qualitative insights into the daily lived experience of individuals with DMD treated with givinostat and their caregivers. The findings are expected to contribute to the design of future trials and support regulatory and reimbursement decision-making by capturing patient- and caregiver-prioritised aspects of functioning and independence. This work also highlights the challenges of measuring quality of life in a progressive disease such as DMD, where continued decline may occur despite therapeutic benefit."

Clinical • HEOR • Interview • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

PROVIDUS: A Study Evaluating the Real-World Experience of Givinostat in Patients With Duchenne Muscular Dystrophy (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: ITF Therapeutics LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Real-world evidence • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

New Data Presented on Givinostat for Treatment of Duchenne Muscular Dystrophy at 2025 World Muscle Society Congress (The Manila Times)

Clinical data • Muscular Dystrophy

Givinostat inhibits in vitro differentiation of cardiac fibroadipogenic precursors from a mouse model of arrhythmogenic cardiomyopathy. (PubMed, Biomed Pharmacother) - "In parallel, cells cultured under pro-fibrotic conditions showed decreased expression of genes encoding components of the extracellular matrix (Col1a1, Col6a1 and Postn) upon givinostat treatment. Overall, these results support the potential of givinostat in modulating cFAP proliferation and differentiation in vitro, warranting further in vivo studies to assess its impact on fibro-fatty tissue replacement in ACM."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Heart Failure • Metabolic Disorders • CEBPA • COL1A1 • COL6A1 • DSG2 • POSTN • PPARG

Italfarmaco Announces Exclusive Distribution Agreement with Multicare Pharma for DMD Treatment Givinostat in Brazil (GlobeNewswire) - "Multicare Pharma will support the regulatory approval in Brazil and distribute givinostat (Duvyzat), Italfarmaco’s novel histone deacetylase (HDAC) inhibitor to treat Duchenne muscular dystrophy (DMD). According to the terms of the agreement, Multicare will manage supply and distribution operations for the drug within Brazil. No financial terms were disclosed."

Commercial • Duchenne Muscular Dystrophy

Novel Therapies in Essential Thrombocythemia and Polycythemia Vera (SOHO 2025) - P1, P1/2, P2, P3 | "In PV, recommended cytoreductive options include hydroxyurea, pegIGN, ropeginterferon-alpha-2b (ropeginterferon), and ruxolitinib...A novel fully human IgG1 monoclonal antibody against mutant CALR (INCA033989) has demonstrated promising preclinical activity...Another phase 1 trial evaluating JNJ-88549968, a novel bispecific antibody that binds to both mutant CALR and T cells to enhance cytotoxicity, 10 is also enrolling both CALR -mutated ET and MF patients (NCT06150157)...12 A phase 2 trial of bomedemstat in high-risk ET patients who were resistant or intolerant to hydroxyurea demonstrated that 94% (34/36) of patients met hematologic response criteria after a median of 8 weeks, with stable hemoglobin levels and improved white blood cell counts...Novel Therapies in Polycythemia Vera Rusfertide and Hepcidin Mimetics Maintenance of a hematocrit <45% is a core aspect of PV therapy, which can be accomplished with a combination of therapeutic phlebotomy..."

IO biomarker • Chronic Myeloid Leukemia • Essential Thrombocythemia • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • CALR • JAK2 • KLK7 • MPL • TMPRSS6

PROVIDUS: A Study Evaluating the Real-World Experience of Givinostat in Patients With Duchenne Muscular Dystrophy (clinicaltrials.gov) - P=N/A | N=300 | Not yet recruiting | Sponsor: ITF Therapeutics LLC

New trial • Real-world evidence • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Epigenetic small molecule screening identifies a new HDACi compound for ameliorating Duchenne muscular dystrophy. (PubMed, Mol Ther Nucleic Acids) - "Certain histone deacetylase inhibitors (HDACi) have been shown to ameliorate DMD phenotypes in mouse and zebrafish models, and the HDACi givinostat has recently gained FDA approval for DMD...Our results add to the growing evidence that HDACi are promising candidates for treating DMD. Our study also provides further support for the effectiveness of small molecule screening in dmd zebrafish."

Journal • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Old Therapy, New Questions: Rethinking Phlebotomy in a Pharmacologic Landscape. (PubMed, Pharmaceuticals (Basel)) - "The emergence of disease-modifying agents-such as interferons, JAK inhibitors, hepcidin mimetics, and epigenetic modulators like givinostat and bomedemstat-promises more sustained hematologic control with the potential to reduce or eliminate the need for repeated phlebotomies. While phlebotomy remains indispensable in early-stage or low-risk PV, its future utility will likely shift toward complementary or bridge therapy in the context of individualized, pharmacologically driven strategies, redefining the role of phlebotomy in the era of precision medicine."

Journal • Review • Genetic Disorders • Hematological Disorders • Polycythemia Vera

Long-Term Evaluation of Givinostat in Duchenne Muscular Dystrophy, and Natural History Comparisons. (PubMed, Ann Clin Transl Neurol) - P2/3 | "Overall, the safety and tolerability of long-term administration of givinostat in patients with DMD was consistent with previous studies. Comparisons with natural history data suggest that givinostat delays the occurrence of major disease progression milestones."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Safety and Efficacy of Givinostat for patients with Muscular dystrophy: A Systematic review. (PubMed, Pharmacology) - "Givinostat offers potential as a disease-modifying therapy for DMD but requires further investigation to establish its role in BMD."

Journal • Review • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Dyslipidemia • Fibrosis • Genetic Disorders • Hematological Disorders • Hypertriglyceridemia • Immunology • Muscular Dystrophy • Thrombocytopenia

ITF Therapeutics LLC…announced publication of positive long-term safety and efficacy data for givinostat as a treatment for Duchenne muscular dystrophy (DMD) from the company's open-label extensions of its Phase 2 and Phase 3 (EPIDYS) trials. (PRNewswire) - "...long-term treatment with givinostat, a novel histone deacetylase (HDAC) inhibitor, in combination with corticosteroids, delayed disease progression in ambulant patients aged six years and older with DMD....The data suggest that givinostat may delay the loss of the ability to rise from the floor by a median of 2.0 years, loss of the ability to climb four stairs (4SC) by 3.3 years, and loss of the ability to walk by 2.9 years...Givinostat was generally well-tolerated across all cohorts in this open-label extension study, and no new safety signals emerged during long-term treatment."

Clinical data • Duchenne Muscular Dystrophy

Italfarmaco Presents New Cardiac Data for Givinostat at 16th European Paediatric Neurology Society (EPNS) Congress (GlobeNewswire) - P3 | N=179 | EPIDYS (NCT02851797) | Sponsor: Italfarmaco | "Italfarmaco S.p.A. announced today that new cardiac data for givinostat, a novel histone deacetylase (HDAC) inhibitor, in ambulant boys with Duchenne muscular dystrophy (DMD) will be presented at the European Paediatric Neurology Society (EPNS) Congress, taking place July 8 - 12, 2025 in Munich, Germany. Post hoc analysis from the completed Phase 3 EPIDYS trial showed less decline in cardiac function throughout the study, compared to those who received placebo. In addition, the analysis showed no prolongation of the QTc interval in either the placebo or givinostat treatment groups. In a separate crossover study conducted by Italfarmaco in healthy volunteers to assess the impact of a therapeutic and supratherapeutic dose of givinostat, the administration of the therapeutic dose was not associated with any risk of QTc interval prolongation."

P3 data • Duchenne Muscular Dystrophy

Assessing the selective impact of histone modifying drugs on adenoid cystic carcinoma cells and their stem cell counterparts. (PubMed, BMC Cancer) - "These findings demonstrate that CSCs and non‑CSCs respond differently to epigenetic modulation, suggesting that personalized combination therapies targeting both subpopulations may be necessary to improve treatment outcomes for ACC. Although these targeted therapies are still in the early stages of investigation, our study provides a promising pre-clinical foundation for the development of effective, personalized therapeutic strategies for this challenging malignancy."

Journal • Adenoid Cystic Carcinoma • Oncology • Salivary Gland Cancer • EGFR