RegulationPriority Review (United States), Fast Track (United States), Orphan Drug (United States), Orphan Drug (European Union), Orphan Drug (Japan), Conditional marketing approval (European Union), Rare Pediatric Disease (United States)

Structure/Sequence

Molecular FormulaC24H30ClN3O5

InChIKeyFKGKZBBDJSKCIS-UHFFFAOYSA-N

CAS Registry732302-99-7

Clinical Trials associated with Givinostat Hydrochloride

JPRN-jRCT2071260086

/ RecruitingPhase 2

A Multicenter, Open-Label Phase 2 Study to evaluate safety and pharmacokinetics of givinostat in Japanese patients with Duchenne Muscular Dystrophy

Start Date31 Aug 2026

Sponsor / Collaborator

JCR Pharmaceuticals Co., Ltd.

NCT06736223

/ CompletedPhase 1

A Multicentric, Open-label, Non-randomized Study to Evaluate the Pharmacokinetic, Safety and Tolerability of ITF2357 Given as an Oral Single 50 mg Dose in Participants With Chronic Hepatic Impairment Relative to Matched Participants With Normal Hepatic Function

This was a multicentric, open-label, non-randomized study to evaluate the pharmacokinetic, safety and tolerability of ITF2357 in participants with chronic hepatic impairment relative to matched participants with normal hepatic function.

Start Date29 May 2025

Sponsor / Collaborator

Italfarmaco SpA

[+1]

NCT06769633

/ RecruitingPhase 2

A Phase 2 Open-label (Core Phase Plus Extension Phase) With 2 Cohorts Study to Assess the Pharmacokinetics and Safety of Givinostat in DMD Patients Ages From at Least 2 Years to Less Than 6 Years Old

This is a Phase 2 Open-label (Core Phase Plus Extension Phase) With 2 Cohorts Study to Assess the Pharmacokinetics and Safety of Givinostat in younger DMD Patients.
* Planned screening duration: approximately 4 weeks
* Planned Core Treatment duration: approximately 48 weeks
* Planned Extension Treatment duration: approximately 96 weeks
* Planned Follow Up duration: approximately 4 weeks (? 7 days)
* Total duration of study participation: up to 151 weeks (ie, 37-38 months)

Start Date02 Jan 2025

Sponsor / Collaborator

Italfarmaco SpA

[+1]

100 Clinical Results associated with Givinostat Hydrochloride

100 Translational Medicine associated with Givinostat Hydrochloride

100 Patents (Medical) associated with Givinostat Hydrochloride

249

Literatures (Medical) associated with Givinostat Hydrochloride

01 Dec 2026·MOLECULAR BIOLOGY REPORTS

ITF2357 exerts anti‑tumor activity in colorectal cancer via the miR‑1938/ADAM12 axis

Article

Author: Xiao, Hongbing ; Jiapaer, Zeyidan ; Maimaiti, Yusupujiang ; Yakupu, Zulihumaer ; Salikebai, Baligen ; Wang, Zhili ; Daoken, Yeerbulati ; Wang, Ting ; Mahemuti, Mairepati ; Zhang, Baoming ; Zhang, Lingying ; Shi, Xiaojing

PURPOSE:

Histone deacetylase inhibitors (HDACi) have emerged as promising anticancer agents. This study aimed to investigate the antitumor efficacy and molecular mechanism of ITF2357 (Givinostat), a novel HDACi, in colorectal cancer (CRC).

METHODS:

In vitro, CT26 cell viability, proliferation, colony formation, and cell cycle distribution were assessed. In vivo, a subcutaneous CT26 tumor model was established in female BALB/c mice to evaluate the antitumor effect of ITF2357. Multi-omics analysis (miRNA-seq, mRNA-seq, ATAC-seq) was performed to identify key regulatory molecules, followed by qRT-PCR, dual-luciferase reporter, and knockdown assays for mechanistic validation.

RESULTS:

ITF2357 significantly inhibited CT26 cell proliferation and induced G0/G1 phase arrest. In vivo, ITF2357 suppressed tumor growth without affecting body weight or liver and kidney tissues, suggesting no obvious systemic toxicity. Multi-omics analysis revealed that ITF2357 upregulated miR-1938, which directly targeted the 3'-UTR of ADAM12. ADAM12 knockdown phenocopied the anti-proliferative and cell cycle arrest effects of ITF2357. Clinically, high ADAM12 expression correlated with poor prognosis in CRC patients.

CONCLUSION:

ITF2357 exerts anti-CRC activity by upregulating miR-1938 to suppress ADAM12, leading to cell cycle arrest. These findings provide new mechanistic insights into the anti-CRC effects of ITF2357 and establish a foundation for exploring its therapeutic potential in CRC.

01 Sep 2026·Molecular Therapy-Nucleic Acids

Givinostat enhances antisense oligonucleotide efficacy in the mdx52 model of Duchenne muscular dystrophy

Article

Author: Spitali, Pietro ; Gastaldi, Cecile ; Mottais, Astrid ; Garcia, Luis ; Doisy, Mathilde ; Goyenvalle, Aurélie ; Le Coz, Olivier ; Phongsavanh, Xaysongkhame ; de Haan, Sandra

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, with deletions within the exon 45-55 hotspot being the most common. Despite advances in antisense oligonucleotide (ASO)-mediated exon skipping, therapeutic efficacy remains limited by suboptimal transcript availability and delivery barriers. We investigated whether histone deacetylase inhibitors (HDACis), particularly givinostat, can enhance the efficacy of an exon 51-targeting ASO in the clinically relevant mdx52 mouse model. For the first time, we identified a pronounced 5'-3' DMD transcript imbalance associated with exon 52 deletion, contrasting with the classical mdx model and potentially compromising ASO effectiveness. In human DMD myoblasts carrying an exon 52 deletion, givinostat significantly improved exon skipping and dystrophin restoration. In vivo, givinostat and ASO co-treatment resulted in a modest but significant increase in dystrophin levels compared to ASO alone (1.3-fold), along with reduced muscle fibrosis, improved fiber morphology, and better extracellular matrix organization. Notably, treated mice showed improved muscle function, as evidenced by a significant reduction in force loss after eccentric contractions, a clinically meaningful outcome. Although the precise molecular mechanisms underlying these effects remain to be fully elucidated, these findings support the therapeutic potential of combining givinostat with ASOs to enhance dystrophin restoration and muscle preservation in DMD.

01 Jun 2026·CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL

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

Review

Author: Owens, Katie ; Argon, Sophie ; Yu, Jingjing ; Ragueneau-Majlessi, Isabelle ; Wang, Yan

Objective:

This analysis aimed to provide a mechanistic understanding and an evaluation of the clinical relevance of pharmacokinetic drug-drug interactions (DDIs) associated with drugs approved by the Food and Drug Administration in 2024.

Methods:

Drug metabolism, transport, and absorption-based DDI data available in New Drug Applications (NDAs) of small molecular drugs approved (n = 34) was analyzed. The mechanism and clinical outcome of these interactions were characterized based on in vitro, in silico, and clinical data.

Results:

As objects, 11 drugs were identified as clinical substrates. 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. All clinical DDIs with AUC changes ≥ 2-fold triggered labeling recommendations. 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.

Conclusions:

Mechanistic DDI insights from newly approved therapies can be extrapolated to inform the management of commonly co-administered drugs, supporting a safer and more effective use of new drug products in the context of polypharmacy.

News (Medical) associated with Givinostat Hydrochloride

02 Oct 2026

·www.biospace.com

Italfarmaco and JCR Pharmaceuticals Enter into Exclusive License Agreement for the Development and Potential Commercialization of Novel Investigational Therapy for Hunter Syndrome in the United States, Europe, and Latin America

- JR-141 is a potentially transformative therapy designed to deliver enzymes to the brain and peripheral tissues to treat neuronopathic and somatic symptoms of Hunter syndrome through intravenous administration - JCR is conducting a global Phase III clinical trial evaluating JR-141 in Hunter syndrome - Italfarmaco will exclusively commercialize JR-141 in the United States, Europe, and Latin America upon regulatory approval MILAN & HYOGO, Japan--(BUSINESS WIRE)-- Italfarmaco S.p.A. (“Italfarmaco”) and JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”) today announced an exclusive license agreement to develop and commercialize JR-141 in the United States, Europe, and Latin America (“licensed territories”) upon regulatory approval. JR-141 is a blood-brain barrier (BBB) penetrating enzyme replacement therapy currently in Phase III ( NCT04573023 ) evaluation as a treatment of Hunter syndrome (also known as mucopolysaccharidosis type II or MPS II). Approved and launched in Japan in 2021 as IZCARGO™ (INN: pabinafusp alfa), JCR and Italfarmaco seek to obtain regulatory approval for JR-141 from the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), and the Brazilian Health Regulatory Agency (ANVISA). Following regulatory approvals by the FDA, EMA, MHRA and ANVISA, Italfarmaco will commercialize and distribute the product in the licensed territories, while JCR will retain responsibility for manufacturing JR-141 upon marketing authorizations. JCR will receive upfront, milestone and royalty payments, in addition to revenues associated with product supply. JR-141 is a next-generation recombinant fusion protein of an antibody against the human transferrin receptor and iduronate-2-sulfatase, the enzyme that is missing or malfunctioning in individuals with Hunter syndrome. JR-141 was developed using J-Brain Cargo ® , JCR’s proprietary BBB-penetration technology. J-Brain Cargo ® is engineered to transport the therapeutic enzyme across the BBB to directly reach the brain and address both the somatic and neuronopathic symptoms of the disease, which can lead to progressive cognitive decline. This agreement expands the relationship between JCR and Italfarmaco, which entered into an exclusive license agreement in December 2025 for the commercialization of givinostat in Japan, a treatment for Duchenne muscular dystrophy, together with a strategic partnership agreement for rare disease therapies. “We are pleased to enter into this strategic agreement with Italfarmaco and collaborate with an ideal global commercialization partner as we work toward our goal of delivering JR-141 to people living with Hunter syndrome around the world,” said Hiroyuki Sonoda, Ph.D., President and Chief Scientific Officer of JCR Pharmaceuticals. “Italfarmaco has expertise in developing and commercializing therapies worldwide, and we look forward to working with Italfarmaco to make JR-141 available to patients outside Japan as soon as possible. This agreement extends our commitment to the partnership with Italfarmaco, developing therapies for rare and genetic diseases for patients around the globe.” “This agreement marks an important milestone in the relationship between Italfarmaco and JCR Pharmaceuticals and reflects a shared commitment to advancing innovative therapies for people living with rare and genetic diseases,” said Francesco Di Marco, Chief Executive Officer of Italfarmaco Group. “By bringing together JCR’s pioneering expertise in blood-brain barrier technologies and Italfarmaco’s global capabilities in rare disease development and commercialization, we are creating a strong foundation to accelerate innovation for underserved patient communities.” “Building on the success of our existing collaboration in Duchenne muscular dystrophy, this agreement further strengthens our partnership and reinforces our shared ambition to be a leading force in the rare and genetic disease field,” said Antonio Nardi, Vice President and Head of Business & Portfolio Development of Italfarmaco. “Alongside our trusted partner, we look forward to advancing our mission of delivering transformative treatments to the patients and families who need them most.” The upfront payment under this agreement has been incorporated into JCR’s consolidated earnings forecast for the fiscal year ending March 31, 2027. About the J-Brain Cargo ® Platform Technology JCR Pharmaceuticals has developed a proprietary blood-brain barrier (BBB)-penetrating technology, J-Brain Cargo ® , to bring biotherapeutics into the central nervous system (CNS). The first drug developed based on this technology is IZCARGO™ (INN: pabinafusp alfa), which is approved in Japan for the treatment of Hunter syndrome, a lysosomal storage disorder (LSD). With J-Brain Cargo ® , JCR seeks to address the unresolved clinical challenges of LSDs by delivering the enzyme to both the body and the brain. About Hunter Syndrome (Mucopolysaccharidosis Type II, or MPS II) Hunter syndrome (mucopolysaccharidosis type II, or MPS II) is an X-linked recessive lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase, an enzyme that breaks down complex carbohydrates called glycosaminoglycans (GAGs, also known as mucopolysaccharides) in the body. Hunter syndrome, which affects an estimated 2,000-3,000 individuals worldwide (according to JCR research), gives rise to a wide range of somatic and neurological symptoms. The current standard of care for Hunter syndrome is enzyme replacement therapy, which does not address the central nervous system-related symptoms of this lysosomal disease. About JR-141 JR-141 (pabinafusp alfa) is a recombinant fusion protein of an antibody against the human transferrin receptor and iduronate-2-sulfatase, the enzyme that is missing or malfunctioning in subjects with Hunter syndrome. It incorporates J-Brain Cargo ® , JCR’s proprietary blood-brain barrier (BBB)-penetrating technology, to cross the BBB through transferrin receptor-mediated transcytosis, and its uptake into cells is mediated through the mannose-6-phosphate receptor. This novel mechanism of action is expected to make pabinafusp alfa effective against the central nervous system (CNS) symptoms of Hunter syndrome. In pre-clinical trials, JCR has confirmed both high-affinity binding of pabinafusp alfa to transferrin receptors and passage across the BBB into neuronal cells. In addition, JCR has confirmed enzyme uptake in various brain tissues. The company has also confirmed a reduction of substrate accumulation in the CNS and peripheral organs in an animal model of Hunter syndrome. 1,2 In several clinical trials of pabinafusp alfa, JCR obtained evidence of reducing heparan sulfate (HS) concentrations in the cerebrospinal fluid (CSF), a biomarker for assessing effectiveness against CNS symptoms; these results were consistent with those obtained in pre-clinical studies. 3 Clinical studies have also demonstrated the positive effects of pabinafusp alfa on CNS symptoms. 4,5,6 Pabinafusp alfa was approved in Japan by the Ministry of Health, Labour and Welfare and marketed since May 2021 under the brand name “IZCARGO™ I.V. Infusion 10mg.” It was also approved in the United Arab Emirates (UAE) in 2026. Important Safety Information INDICATION: IZCARGO™ is indicated for the treatment of mucopolysaccharidosis type II (MPS II), which is also known as Hunter syndrome. IZCARGO™ is approved in Japan and the United Arab Emirates (UAE). CONTRAINDICATION: IZCARGO™ is contraindicated in patients with a history of anaphylactic shock to its components. WARNINGS AND PRECAUTIONS: Warnings Since serious anaphylaxis and shock may occur with use of IZCARGO™, adequate emergency measures should be made ready for execution before initiation of administration, and the patient should be closely monitored during and after the administration. If a serious infusion associated reaction (IAR) occurs, administration of IZCARGO™ should be discontinued, and appropriate actions should be taken. When IZCARGO™ is administered to patients with severe respiratory failure or acute respiratory disease, an IAR may lead to acute exacerbation of symptoms. A patient’s condition should be closely monitored, and appropriate actions should be taken as needed. Precautions for Use IZCARGO™ is a protein medicinal product and may cause anaphylactic shock, for which close monitoring is required. If any signs of anaphylaxis are noted, discontinue the infusion, and take appropriate actions. Considering the onset of such symptoms, emergency measures should be made ready for execution. IZCARGO™ may cause IARs such as headache, chills, syncope, fatigue, dizziness, pyrexia, rash, erythema, urticaria, or other symptoms. If an IAR occurs, reduce the rate or temporarily discontinue the infusion, and initiate appropriate drug treatment (e.g., corticosteroids, antihistamines, antipyretic analgesics, anti-inflammatory drugs) or emergency procedures (e.g., oxygen administration, securing of airway, adrenaline administration). Premedication with antihistamines, corticosteroids, etc., should be considered for the subsequent infusion of IZCARGO™. ADVERSE REACTIONS: The most commonly reported adverse reactions were pyrexia and urticaria. Prescribing information, indications, contraindications, warnings, and adverse reactions may differ by jurisdiction. Healthcare professionals should consult the locally approved prescribing information. About Italfarmaco S.p.A. Founded in 1938 in Milan, Italy, Italfarmaco is a private global pharmaceutical company that has led the successful development and approval of many pharmaceutical products around the world. The Italfarmaco group has operations in more than 90 countries through directly controlled or affiliated companies. The company is a leader in pharmaceutical research, product development, production and commercialization with proven success in multiple therapeutic areas including oncology, gynecology, neurology, cardiovascular disease and rare diseases. Italfarmaco’s rare disease unit includes programs in Duchenne muscular dystrophy, Becker muscular dystrophy, amyotrophic lateral sclerosis and polycythemia vera. About JCR Pharmaceuticals Co., Ltd. JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceutical company that develops treatments that go beyond rare diseases to solve the world’s most complex healthcare challenges. We continue to build upon our 50-year legacy in Japan while expanding our global footprint into the U.S., Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. Our core values – Putting people first, Forging our own path, Always advancing, and Committed to excellence – mean that the work we do benefits all our stakeholders, including partners, patients and employees. We strive to expand the possibilities for patients while accelerating medical advancement at a global level. For more information, please visit JCR’s global website: . Cautionary Statement Regarding Forward-Looking Statements This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future. References: Sonoda, et al. A blood-brain-barrier-penetrating anti-human transferrin receptor antibody fusion protein for neuronopathic mucopolysaccharidosis II. Mol. Ther. 2018; 26(5): 1366-1374. Morimoto, et al. Clearance of heparin sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice. Mol. Ther. 2021; 29(5): 1853-1861. Okuyama, et al. Iduronate-2-sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1/2 Trial. Mol Ther. 2020; 27(2): 456-464. Okuyama, et al. A Phase 2/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II. Mol Ther. 2021; 29(2): 671-679. Giugliani, et al. Iduronate-2-sulfatase fused with anti-human transferrin receptor antibody, pabinafusp alfa, for treatment of neuronopathic and non-neuronopathic mucopolysaccharidosis II: Report of a phase 2 trial in Brazil. Mol Ther. 2021; 29(7): 2378-2386. Giugliani, et al. Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II; an Integrated Analysis of Preclinical and Clinical Data. Int. J. Mol. Sci. 2021, Volume 22, Issue 20, 10938. Contacts Media enquiries - Italfarmaco: Gretchen Schweitzer / Adolfo Luna | +49 (0) 151 626 74395 | italfarmaco@trophic.eu Other enquiries - Italfarmaco: Samantha Parker | Patient Advocacy and Communications Lead | RDEnquiries@italfarmacogroup.com Investors & Media - JCR Pharmaceuticals Co., Ltd.: Corporate Communications ir-info@jp.jcrpharm.com

Phase 2Drug ApprovalLicense out/inPhase 3

30 Sep 2026

·www.biospace.com

Italfarmaco Presents New Givinostat (Duvyzat®) Clinical Data Supporting Preservation of Upper Limb Function in Duchenne Muscular Dystrophy Patients at the 2026 World Muscle Society Congress

New data suggest that givinostat treatment may slow the decline of upper limb function in boys with Duchenne muscular dystrophy compared with modelled external comparator disease trajectories derived from a single centre natural history study Findings further expand the growing body of evidence supporting the potential long-term clinical benefits of givinostat across multiple measures of disease progression MILAN, Italy, September 30, 2026 – Italfarmaco S.p.A. today announced new long-term data from the ongoing Phase 3 EPIDYS open-label extension (OLE) study showing that treatment with givinostat (Duvyzat ® ) may help preserve upper limb function in boys with Duchenne muscular dystrophy (DMD). The findings, presented at the 31st Annual International Congress of the World Muscle Society (WMS), provide further evidence supporting the long-term clinical benefits of givinostat across multiple measures of disease progression. John Brandsema, MD, Paediatric Neurologist in the Division of Neurology at Children’s Hospital of Philadelphia, presented the poster "Trajectory of Performance of Upper Limb in Patients With Duchenne Muscular Dystrophy Treated With Givinostat Relative to a Modeled Natural History Cohort from a Single Centre," which compared upper limb function in givinostat-treated patients with counterfactual trajectories estimated from an external natural history-based model representing predicted disease progression in the absence of treatment, using the Performance of Upper Limb 2.0 (PUL 2.0) assessment. Upper limb function is an increasingly important measure of disease progression as DMD advances and loss of ambulation occurs. “Preserving upper limb function is critically important for people living with Duchenne because it directly affects independence and the ability to perform everyday activities,” said Scott Baver, PhD, VP, Head of Global Medical Affairs, Rare Diseases. “These new findings extend our understanding of givinostat beyond ambulatory outcomes and provide exploratory evidence suggesting a potential effect on the preservation of upper limb function, an important aspect of disease progression for people living with DMD.” “Upper limb function becomes increasingly important as Duchenne progresses because it has a direct impact on independence and participation in daily life,” said John Brandsema, MD, Paediatric Neurologist at Children’s Hospital of Philadelphia and presenter of the analysis. “Preserving upper limb function is an outcome that matters greatly to patients and families.” Key findings: These exploratory analyses compared observed outcomes in patients receiving givinostat with predicted outcomes generated from an external natural history-based model and should be interpreted within the context of this study design. Patients were assessed based on PUL 2.0 evaluations: 115 patients were evaluable for the 12-month analysis. In this cohort, the observed mean change in PUL 2.0 score was –0.78, compared with an average predicted decline of –4.57 (a difference of 3.79; nominal p<0.001) based on the model developed using natural history data In the cohort evaluable at 24 months (n=96), the observed mean change in PUL 2.0 score was –2.26, compared with an average predicted decline of –8.55 (a difference of 6.29; nominal p<0.001) These findings suggest that patients receiving givinostat experienced a slower average decline in upper limb function than predicted based on counterfactual trajectories Abstract details are available under poster session 2, poster ID 2.041eP, in the 2026 WMS Congress programme . About Givinostat Givinostat was discovered through Italfarmaco’s research and development efforts in collaboration with Telethon and Duchenne Parent Project (Italy). Givinostat is an orally administered histone deacetylase (HDAC) inhibitor that regulates the excessive HDAC activity characteristic of DMD muscles. By doing so, it helps restore the expression of key genes and biological processes essential for muscle maintenance and repair. Its mechanism of action is independent of the specific dystrophin gene mutation causing the disease. The EPIDYS Phase 3 study is a randomized, placebo-controlled clinical trial designed to evaluate the efficacy and safety of givinostat in patients with DMD. MRI-based assessments of muscle composition were included as exploratory endpoints to better characterize disease progression. The ongoing open-label extension (OLE) study is intended to provide additional information on longer-term outcomes in patients previously enrolled in clinical trials. Givinostat is approved as a treatment of DMD in multiple regions, including the US and EU, for patients aged 6 years and older, with differences across regions in ambulatory status criteria. About ITALFARMACO Founded in 1938 in Milan, Italy, Italfarmaco is a private global pharmaceutical company that has led the successful development and approval of many pharmaceutical products around the world. The Italfarmaco group has operations in more than 90 countries through directly controlled or affiliated companies. The company is a leader in pharmaceutical research, product development, production and commercialisation with proven success in many therapeutic areas including immuno-oncology, gynaecology, neurology, cardiovascular disease and rare diseases. Italfarmaco's rare disease unit includes programmes in Duchenne muscular dystrophy, Becker muscular dystrophy, amyotrophic lateral sclerosis and polycythaemia vera. For more information visit . Intended Audiences Notice This press release is issued from our Corporate Headquarters in Milan, Italy and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country. Media enquiries: Anja Heuer / Adolfo Luna |+49 (0) 151 106 199 05 | italfarmaco@trophic.eu Other enquiries: Samantha Parker |Patient Advocacy and Communications Lead| RDEnquiries@italfarmacogroup.com Attachment Italfarmaco Presents New Givinostat (Duvyzat®) Clinical Data Supporting Preservation of Upper Limb Function in Duchenne Muscular Dystrophy Patients at the 2026 World Muscle Society Congress

Phase 3Clinical Result

28 Sep 2026

·www.biospace.com

JCR Pharmaceuticals Receives Orphan Drug Designation from the Ministry of Health, Labour and Welfare of Japan for Givinostat for Duchenne Muscular Dystrophy

HYOGO, Japan--(BUSINESS WIRE)-- JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”) today announced that the Ministry of Health, Labour and Welfare of Japan granted orphan drug designation to givinostat, an investigational drug for the treatment of Duchenne muscular dystrophy (DMD). Givinostat (marketed as Duvyzat ® in the US, EU, and the UK) is an orally administered histone deacetylase (HDAC) inhibitor developed by Italfarmaco S.p.A. It has been approved in multiple countries and regions, including the US, EU, and the UK, and is prescribed to patients aged 6 years and older with DMD in accordance with local prescribing information. It is currently not approved in Japan. In December 2025, JCR entered into an exclusive license agreement with Italfarmaco for the development and commercialization of givinostat in Japan. JCR is currently advancing development toward obtaining marketing approval in Japan and plans to submit a marketing authorization application for the product in Japan by the end of 2026. In addition to receiving orphan drug designation in Japan, givinostat has also been granted Priority Examination status. “The designation of givinostat as both an orphan drug and a product eligible for Priority Examination represents an important milestone toward its commercialization in Japan,” said Hiroyuki Sonoda, Ph.D., President and Chief Scientific Officer of JCR Pharmaceuticals. “We remain committed to bringing this new treatment option to patients with DMD in Japan as quickly as possible, addressing the significant unmet medical needs of the DMD community.” JCR remains committed to advancing research and development to help meet the expectations of patients and families waiting for effective treatment options. About Orphan Drug Designation in Japan Under the orphan drug designation system, the Ministry of Health, Labour and Welfare of Japan takes special measures to support and promote research activities for the development of drugs for rare diseases. Drugs satisfying the following criteria may be designated as orphan drugs: they are targeting a condition with an incidence of fewer than 50,000 patients in Japan, or their intended use is for the treatment of a designated intractable disease. The drugs should be indicated for the treatment of serious diseases including difficult-to-treat diseases for which there are high unmet medical needs, such as there is no approved medicinal product or higher efficacy, or safety is expected compared with an approved medicinal product. Moreover, the applicant for orphan drug designation needs to have enough resources and plans for development of its product as an orphan drug in Japan. About Duchenne Muscular Dystrophy (DMD) Duchenne muscular dystrophy (DMD) is a rare, progressive neuromuscular disorder caused by mutations in the dystrophin gene. These mutations prevent the production of functional dystrophin, causing the dystrophin-associated protein complex (DAPC) to break down. This makes muscle fibres more vulnerable to damage and increases histone deacetylase (HDAC) levels in the muscle cells, blocking the activation of important genes needed for muscle maintenance and repair. As a result, muscle fibres experience ongoing damage, leading to chronic inflammation and poor regeneration. Over time, muscle cells die and are replaced by scar tissue and fat. 1-4 DMD primarily affects males, with symptoms typically appearing between the ages of two and five years. As the condition progresses, muscle weakness worsens, leading to difficulty walking and eventually loss of ambulation. Over time, the heart and respiratory muscles are also affected, which are the leading causes of premature death. 5 DMD is one of the most severe and common forms of childhood muscular dystrophy, with a global birth incidence of approximately 1 in 5,050 boys. 6 DMD affects an estimated 3,500 patients in Japan. 7 About Givinostat Givinostat (Duvyzat ® ) was discovered through Italfarmaco’s research and development efforts in collaboration with Telethon and Duchenne Parent Project (Italy). Givinostat is an orally administered histone deacetylase (HDAC) inhibitor that regulates the excessive HDAC activity characteristic of DMD muscles. By doing so, it helps restore the expression of key genes and biological processes essential for muscle maintenance and repair. Its mechanism of action is independent of the specific dystrophin gene mutation causing the disease. About Italfarmaco S.p.A. Founded in 1938 in Milan, Italy, Italfarmaco is a private global pharmaceutical company that has led the successful development and approval of many pharmaceutical products around the world. The Italfarmaco group has operations in more than 90 countries through directly controlled or affiliated companies. The company is a leader in pharmaceutical research, product development, production and commercialization with proven success in multiple therapeutic areas including oncology, gynecology, neurology, cardiovascular disease and rare diseases. Italfarmaco's rare disease unit includes programs in Duchenne muscular dystrophy, Becker muscular dystrophy, amyotrophic lateral sclerosis and polycythemia vera. About JCR Pharmaceuticals Co., Ltd. JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceutical company that develops treatments that go beyond rare diseases to solve the world’s most complex healthcare challenges. We continue to build upon our 50-year legacy in Japan while expanding our global footprint into the U.S., Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. Our core values – Putting people first, Forging our own path, Always advancing, and Committed to excellence – mean that the work we do benefits all our stakeholders, including partners, patients and employees. We strive to expand the possibilities for patients while accelerating medical advancement at a global level. For more information, please visit JCR’s global website: Cautionary Statement Regarding Forward-Looking Statements This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future. References: Sandonà M, Cavioli G, Renzini A, et al. Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies. Int J Mol Sci. 2023;24(5):4306. Consalvi S, Saccone V, Giordani L, Minetti G, Mozzetta C, Puri PL. Histone Deacetylase Inhibitors in the Treatment of Muscular Dystrophies: Epigenetic Drugs for Genetic Diseases. Mol Med. 2011;17(5):457–465. Bez Batti Angulski A, Hosny N, Cohen H, et al. Duchenne muscular dystrophy: disease mechanism and therapeutic strategies. Front Physiol. 2023;14:1183101. Giuliani G, Rosina M, Reggio A. Signaling pathways regulating the fate of fibro/adipogenic progenitors (FAPs) in skeletal muscle regeneration and disease. FEBS J. 2022;289(21):6484–6517. Walter MC, Reilich P. Recent developments in Duchenne muscular dystrophy: facts and numbers. J Cachexia Sarcopenia Muscle. 2017;8(5):681–685. Crisafulli S, Sultana J, Fontana A, Salvo F, Messina S, Trifirò G. Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet J Rare Dis. 2020;15(1):141. Kawai M. The Number of Patients with Duchenne Muscular Dystrophy in Japan. No To Hattatsu. (Japanese) 2013;45(Supple.):S324. Contacts Investors & Media: JCR Pharmaceuticals Co., Ltd. Corporate Communications ir-info@jp.jcrpharm.com

Orphan DrugLicense out/in

100 Deals associated with Givinostat Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D12742 D12743	Givinostat Hydrochloride	M09AX14	DB12645

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Muscular Dystrophy, Duchenne	United States	Italfarmaco SpA	21 Mar 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Musculoskeletal Diseases	NDA/BLA	Canada	ITF Therapeutics, LLC.	01 Jun 2026
Polycythemia Vera	Phase 3	United States	Italfarmaco SpA	26 Mar 2024
Polycythemia Vera	Phase 3	Austria	Italfarmaco SpA	26 Mar 2024
Polycythemia Vera	Phase 3	Bulgaria	Italfarmaco SpA	26 Mar 2024
Polycythemia Vera	Phase 3	Croatia	Italfarmaco SpA	26 Mar 2024
Polycythemia Vera	Phase 3	France	Italfarmaco SpA	26 Mar 2024
Polycythemia Vera	Phase 3	Germany	Italfarmaco SpA	26 Mar 2024
Polycythemia Vera	Phase 3	Hungary	Italfarmaco SpA	26 Mar 2024
Polycythemia Vera	Phase 3	Ireland	Italfarmaco SpA	26 Mar 2024
Polycythemia Vera	Phase 3	Israel	Italfarmaco SpA	26 Mar 2024

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06736223 (CTgov)	Phase 1	Hepatic Insufficiency	24	ITF2357 (Mild HI)	vwzgsxprbw(tgmujpnqgv) = vieneqemzo gmtgrcuyet (oqeptgkbdf, 33.5) View more	-	18 Jun 2026
NCT06736223 (CTgov)	Phase 1	Hepatic Insufficiency	24	ITF2357 (Moderate HI)	vwzgsxprbw(tgmujpnqgv) = nupjogqylj gmtgrcuyet (oqeptgkbdf, 54.7) View more	-	18 Jun 2026
NCT03373968 (MDA2026)	Phase 3	Muscular Dystrophy, Duchenne	207	Givinostat	cudqhwmnpm(ljgewfqfuq) = ovvyopvzfc cseqxrxfvq (cjdxeghvnz ) View more	Positive	08 Mar 2026
NCT03373968 (MDA2026)	Phase 3	Muscular Dystrophy, Duchenne	207	Delayed Givinostat	cudqhwmnpm(ljgewfqfuq) = rghwlrgvim cseqxrxfvq (cjdxeghvnz ) View more	Positive	08 Mar 2026
EPIDYS (MDA2026)	Phase 3	Muscular Dystrophy, Duchenne	179	Givinostat	judcbckpxz(elxsjcomtw) = pdxfaexido luzfavumna (xwiiavbbrn )	Positive	08 Mar 2026
NCT03373968 (MDA2026)	Phase 3	Muscular Dystrophy, Duchenne	225	Givinostat in combination with corticosteroids	ozffacwlki(gixjrjsjul) = published estimates from a meta-analysis reporting a median age at LoA of 11.0-13.4 years in patients treated with corticosteroids alone talsibxekr (njzdhujprs )	Positive	08 Mar 2026
NCT02851797 (EPIDYS, MDA2026)	Phase 3	Muscular Dystrophy, Duchenne	179	Givinostat	zarkmpfklo(cstmlyvhad) = kneyjfdrwn pwehvpybon (jqrcmzsvgi ) View more	Positive	08 Mar 2026
NCT06093672 (GIV-IN-PV, ASH2025)	Phase 3	Polycythemia Vera JAK2V617F mutation	220	Givinostat	aztbokuecr(xiwnxxodfa) = dxstfaezdh xqtkufnrwm (znadmwiipw ) View more	Positive	06 Dec 2025
NCT06093672 (GIV-IN-PV, ASH2025)	Phase 3	Polycythemia Vera JAK2V617F mutation	220	Hydroxyurea	yyfnkfpytc(tiezqtilpo) = wjfefxqxec ditzcpwgeg (rtmpzahpjz ) View more	Positive	06 Dec 2025
NCT06093672 (ASH2025)	Phase 3	Polycythemia Vera	904	Givinostat	rherxjdxrg(vadacmunst) = zjkixjuzwu pbhahcsiwy (oaozrktiaq )	Positive	06 Dec 2025
NCT03373968 (EPIDYS, Pubmed \| Ann Clin Transl Neurol)	Phase 3	Muscular Dystrophy, Duchenne	194	Givinostat oral suspension + Givinostat oral suspension	insbttuoyt(umnigimmho) = uxrcqzqvye stzsbqcuap (nbcpcsntbv )	Positive	01 Nov 2025
NCT02851797 (EPIDYS, GlobeNewswire) Manual	Phase 3	Muscular Dystrophy, Duchenne	179	Givinostat	bzbrlnadts(xjszmnkvwb) = 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. tpaabufywy (hlcszujtow ) View more	Positive	11 Jun 2025
NCT02851797 (EPIDYS, MDA2025)	Phase 3	Muscular Dystrophy, Duchenne	56	Givinostat in addition to steroids	tomvcoliaz(ersjxwhcnb) = tkizywbwix ygjnpzyfkx (yzufttqruz, 2.2) View more	Positive	16 Mar 2025
NCT02851797 (EPIDYS, MDA2025)	Phase 3	Muscular Dystrophy, Duchenne	56	Steroids only (PRO-DMD-01)	tomvcoliaz(sscxnjywtt) = tndnuwrlim btdittictu (cpqhcywuid, 2.2) View more	Positive	16 Mar 2025

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