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

Thorough QT Study on the Effect of Therapeutic and Supratherapeutic Dosing of Givinostat in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "In the concentration-QTc analysis, an Emax model captured the data better than the prespecified linear model and showed that an effect on ∆∆QTcF exceeding 10 ms could be excluded within the full range of observed givinostat concentrations in this study and up to ≈745 ng/mL. Givinostat at the maximum labeled dose (up to 53.2 mg twice daily for DMD) is not expected to pose a QT prolongation risk."

Clinical • Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Histone deacetylase inhibitor givinostat attenuates metabolic dysfunction-associated steatotic hepatitis and liver fibrosis (APASL 2026) - No abstract available

Epigenetic controller • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders

EXPERT CONSENSUS ON TREATMENT GUIDANCE FOR FDA-APPROVED AND SECOND-GENERATION EXON-SKIPPING THERAPIES IN DUCHENE MUSCULAR DYSTROPHY (DMD): A RAND/UCLA MODIFIED DELPHI PANEL (ISPOR 2026) - "We aimed to characterize the current therapeutic landscape for DMD, including exon-skipping therapies, gene therapy, and givinostat, as well as emerging second-generation exon-skipping agents. Using the RAND/UCLA modified Delphi panel method, nine US experts (seven pediatric neurologists, two physical therapists) rated the likelihood of recommending FDA-approved therapies (eteplirsen, golodirsen, viltolarsen, casimersen, GT, givinostat) and the anticipated clinical value of investigational therapies with Phase 1/2 data (delpacibart zotadirsen, DYNE-251, WVE-N531, and NS-089/NCNP-02)... The panel reached consensus that approved exon-skipping therapies provide modest benefit, particularly in earlier stages, while early data suggest that second-generation exon-skippers may have the potential to offer greater functional improvement. However, trials remain in early stages, and the full risks and benefits of these therapies are not yet known. The findings highlight the rapidly..."

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

Cardiac surveillance in the era of Duvyzat: do we need to do more? (PubMed, Acta Myol) - No abstract available

Journal

Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Italfarmaco | Not yet recruiting ➔ Recruiting

Enrollment open • JAK2V617F • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Myeloproliferative Neoplasm • Oncology

Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Italfarmaco

JAK2V617F • New P2 trial • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Myeloproliferative Neoplasm • Oncology

Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Italfarmaco | N=60 ➔ 90 | Trial primary completion date: Dec 2019 ➔ Jun 2020

Enrollment change • JAK2V617F • Trial primary completion date • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology

Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: Italfarmaco | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Jun 2025 ➔ Dec 2026

JAK2V617F • Trial completion date • Trial primary completion date • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Myeloproliferative Neoplasm • Oncology

Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: Italfarmaco | Trial completion date: Dec 2022 ➔ Dec 2025 | Trial primary completion date: Jun 2022 ➔ Jun 2025

JAK2V617F • Trial completion date • Trial primary completion date • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Myeloproliferative Neoplasm • Oncology

Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: Italfarmaco | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2020 ➔ Dec 2022 | Trial primary completion date: Jun 2020 ➔ Jun 2022

Enrollment closed • JAK2V617F • Trial completion date • Trial primary completion date • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Myeloproliferative Neoplasm • Oncology

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