Givinostat Hydrochloride

10,000-square-foot facility to house corporate offices and serve as a center for meetings and events with members of the Duchenne muscular dystrophy and other rare disease communities CONCORD, Mass., March 5, 2025 /PRNewswire/ -- ITF Therapeutics LLC, the U.S. affiliate of Italfarmaco, today announced the opening of the company's new U.S. headquarters in Concord, Massachusetts. The 10,000-square-foot facility located at 575 Virginia Road, Unit 201, will include corporate offices as well as meeting spaces where ITF will welcome members of the Duchenne muscular dystrophy (DMD) and other rare disease communities. "ITF Therapeutics was founded only one year ago, and in that short time we have rapidly expanded our team to include specialists who are working to make a positive difference for people living with rare diseases and we announced the FDA approval and commercial launch of our first product, DUVYZAT™ (givinostat)," said Matt Trudeau, president, ITF Therapeutics. "Our new U.S. headquarters in Concord will help us continue the momentum, bringing together more of our team members to plan for many exciting new opportunities for our company. The office will also be a welcoming space where members of the communities we serve can share their insights with us to keep their voices front and center in our work." The headquarters will accommodate up to 40 members of the ITF Therapeutics team. In planning the design of the headquarters, ITF worked closely with leaders from the patient advocacy community to understand and incorporate features that support accessibility and comfort for guests. "As we planned for our new office, members of our team at every level stressed the importance of making this a space that reflects our focus on honoring the experiences of people living with DMD and their families," Trudeau added. "We are very much looking forward to hosting community members and creating many new opportunities for them to engage with ITF Therapeutics in meaningful ways." Please see the Indication and Important Safety Information for DUVYZAT below. About DUVYZAT™ (givinostat) DUVYZAT is a U.S. FDA-approved histone deacetylase (HDAC) inhibitor indicated for the treatment of patients six years of age and older with Duchenne muscular dystrophy (DMD) that was discovered through the research and development efforts of Italfarmaco in collaboration with Telethon and Duchenne Parent Project (Italy). HDACs are enzymes located in the body's cells that play a key role in maintaining and repairing muscles. In DMD, the HDAC enzymes become overactive, leading to chronic muscle inflammation, decreased muscle repair, and replacement of muscle with fat and scar tissue. DUVYZAT inhibits HDAC overactivity and is thought to help reduce inflammation, increase the body's ability to repair muscles, and slow muscle loss. For more information visit . About ITF Therapeutics LLC ITF Therapeutics was launched in January 2024 as the U.S. affiliate of Italfarmaco focused on the development and commercialization of products to treat rare diseases. Building on a legacy grounded in collaboration and innovation, ITF Therapeutics strives to partner with leaders from the patient advocacy and treatment communities to ensure that our programs reflect and support their unique needs and goals. The establishment of ITF Therapeutics reflects Italfarmaco's goal to build a world-class team of experts who share a passion to make a positive impact for rare disease communities. For more information visit . 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 commercialization with proven success in many therapeutic areas including immuno-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. For more information visit . Indication and Important Safety Information What is DUVYZAT? DUVYZAT is a prescription medicine that is used for the treatment of Duchenne muscular dystrophy (DMD) in people 6 years of age and older. It is not known if DUVYZAT is safe and effective in children under 6 years of age. Important Safety Information What is the most important information I should know about DUVYZAT? Low platelet counts in your blood (thrombocytopenia). Platelets are important for blood clotting, and a decrease in their numbers can lead to an increased risk of bleeding or bruising. Your healthcare provider will check your blood count before you start DUVYZAT and regularly during treatment for any signs of thrombocytopenia. Call your healthcare provider right away if you notice any unusual bleeding or small red or purple spots on the skin called petechiae. Your healthcare provider may change your dose of DUVYZAT if your blood platelet counts continue to be low or may stop your treatment with DUVYZAT. Increased levels of fat (triglycerides) in your blood. You may not have any symptoms, so your healthcare provider will do blood tests before you start DUVYZAT and regularly during treatment to check your triglyceride levels. Your healthcare provider may change your dose of DUVYZAT if your triglyceride levels continue to be high or may stop your treatment with DUVYZAT. Frequent watery loose stools (diarrhea) and vomiting. DUVYZAT can cause vomiting and moderate to severe diarrhea. If diarrhea occurs, you should keep track of the frequency and severity of your diarrhea symptoms, drink plenty of fluids, and contact your healthcare provider. Your healthcare provider may change your dose of DUVYZAT if the diarrhea cannot be managed or does not go away. Your healthcare provider may also stop your treatment with DUVYZAT. Before taking DUVYZAT, tell your healthcare provider about all of your medical conditions, including if you: have any heart problems or if you take any medicines that could increase your chance for irregular heart rhythms. have any bleeding problems. Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking DUVYZAT with certain other medicines may affect each other. Taking DUVYZAT with other medicines can cause serious side effects. Do not start or stop other medicines without talking to your healthcare provider. DUVYZAT can cause serious side effects, including: See "What is the most important information I should know about DUVYZAT?" Changes in the electrical activity of your heart called QT Prolongation. QT Prolongation can increase the risk of developing a type of irregular heart rhythm known as Torsades de Pointes. Call your healthcare provider right away if you feel faint, have an irregular heartbeat, feel dizzy, or lose consciousness. The most common side effects of DUVYZAT included diarrhea, nausea, vomiting, stomach pain, low platelet counts in the blood, increased fat level in the blood, and fever. These are not all of the possible side effects of DUVYZAT. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please see full Prescribing Information and Medication Guide. DUVYZAT is a registered trademark of Italfarmaco S.p.A. U.S.A. Media inquiries: Brian Connor | +1 212 253 8881 | [email protected] Other inquiries: Patient Advocacy and Communications Lead U.S.A. | [email protected] Global Media inquiries: Charlotte Spitz or Jacob Verghese | +49 (0)151 7441 6179 | [email protected] Other inquiries: Patient Advocacy and Communications Lead | [email protected] C-DUV-US-0318 02/2025 SOURCE ITF Therapeutics LLC WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

iStockphoto/ Olivier Le Moal ITF, IntraBio and Orchard are among the companies that have won FDA nods in the past year for Duchenne muscular dystrophy, Niemann-Pick disease type C, metachromatic leukodystrophy and more. Rare Disease Day, which falls at the end of February each year, is an opportunity to take stock of advances in this space, as well as the many remaining gaps in care and treatment. Defined as diseases that affect fewer than 200,000 people in the U.S., rare diseases collectively afflict about 350 million people worldwide, according to the National Organization for Rare Disorders . An estimated 7,000 of these conditions have been identified, and more than 90% of them have no FDA-approved treatment. Yet progress toward developing such treatments continues, particularly among smaller companies. Here are five rare diseases that have seen drug approvals since last year’s Rare Disease Day. Duchenne Muscular Dystrophy Duchenne muscular dystrophy (DMD) is a relatively common rare disease, affecting about one out of every 3,600 baby boys. This X-linked genetic disease affects the dystrophin protein, a component of muscle, and causes progressive weakening of skeletal and heart muscle. Families affected by DMD saw a spate of treatment approvals in 2023 and 2024, including Sarepta Therapeutics’ Elevidys and Catalyst Pharmaceuticals’ Agamree. The most recent was Duvyzat (givinostat), a small molecule therapy marketed by ITF Therapeutics. It targets histone deacetylases, enzymes that modulate gene and protein expression in the muscle. “Deregulation of HDACs is a major consequence of the lack of dystrophin associated with DMD,” Matt Trudeau, head of ITF, told BioSpace in an email ahead of the FDA decision in March 2024. “We believe givinostat’s mode of action has the potential to inhibit HDAC pathological overactivity and thereby impact the cascade of events leading to muscle damage which, in turn, may counteract disease pathology and slow muscle deterioration.” In the Phase III Epidys trial , givinostat met the primary endpoint of a change in the four-stair climb assessment from baseline to 72 weeks. Italfarmaco, the parent company of ITF which developed the drug, also reported that it showed “favorable outcomes” in key secondary measures, including on the North Star Ambulatory Assessment (NSAA), a scale that measures motor function skills. On the NSAA, patients treated with the new drug saw less worsening compared to placebo after 18 months. Givinostat was generally well tolerated, with no treatment-related severe or serious adverse events. Metachromatic Leukodystrophy Metachromatic leukodystrophy (MLD) is a metabolic disease that affects one in every 100,000 live births. It is caused by a mutation in the arylsulfatase-A ( ARSA ) gene, which codes for an enzyme that breaks down sulfatides, and is characterized by a pathological build-up of sulfatides in the brain, liver, kidneys, spleen and other body parts. Over time this buildup can lead to organ damage and neurological issues, and patients often experience motor, behavioral and cognitive problems, as well as seizures. Most patients die within five years of disease onset. The FDA approved the first therapy for early juvenile or early symptomatic forms of the disease, Lenmeldy (atidarsagene autotemcel), in March 2024. The gene therapy, marketed by Orchard Therapeutics, uses a patient’s own stem cells to deliver a functioning copy of the ARSA gene. Lenmeldy was also approved by the European Union in December 2020 , where it is marketed as Libmeldy. The FDA’s approval of Lenmeldy is backed by data from two single-arm, open-label trials enrolling a total of 37 pediatric MLD patients. Over a median follow-up of 6.76 years, Lenmeldy led to significantly better overall survival compared with natural history data. The gene therapy also preserved motor and cognitive function in late-infantile MLD patients. Lenmeldy’s most common adverse events were febrile neutropenia, stomatitis, respiratory tract infections and rashes. WHIM Syndrome Fewer than 1,000 people in the U.S. have been diagnosed with WHIM syndrome, according to the NIH. The condition’s name is an acronym of the four characteristics of the disease: warts, hypogammaglobulinemia (low antibody levels), infections and myelokathexis (a white blood cell disorder). The syndrome is caused by mutations in the chemokine receptor ( CXCR4 ) gene that increase the activity level of the resulting protein. In April 2024, the FDA approved X4 Pharmaceuticals’ Xolremdi (mavorixafor) as the first targeted treatment for WHIM. Xolremdi is an oral CXCR4 antagonist that draws white blood cells from the bone marrow into the blood to improve immune deficiencies. It is approved for patients 12 and older. Phase III results from the 4WHIM trial of Xolremdi showed a 60% reduction in annualized infection rate compared to placebo; trial participants had less than one infection per year compared with 4.5 for the placebo group. Teresa Tarrant, an associate professor at Duke University’s School of Medicine and lead investigator of the 4WHIM trial, told BioSpace last year that previous treatments for the disease were only supportive. “I think that for a lot of patients, the idea that there is a targeted therapy . . . something that is directly correcting the underlying problem for the individual, I think that gives them a lot of hope, a lot of optimism,” Tarrant said. “I think WHIM is going to be a poster child for rare diseases and the ability where we’re at now in modern medicine to design therapies to treat underlying genetic disorders.” Niemann-Pick Disease Type C Afflicting approximately one in every 150,000 people , Niemann-Pick disease type C (NPC) is an ultrarare lysosomal storage disease that progressively impairs patients’ physical and cognitive function. It is caused by mutations in the NPC1 and NPC2 genes that hinder the body’s ability to clear cholesterol and other lipids from inside cells, leading to their pathologic build-up in the brain and other crucial organs. NPC affects patients’ speech, motor and swallowing functions. According to the FDA , patients with NPC typically live only up to around 13 years of age. September 2024 saw not one, but two approvals of therapies for NPC. The first, Zevra Therapeutics’ Miplyffa (arimoclomol), is an oral drug approved for patients 2 years and older that is intended to be used alongside miglustat , a small molecule approved to treat the neurological manifestations of NPC. According to the company , Miplyffa activates transcriptional factors, resulting in the upregulation of coordinated lysosomal expression and regulation (CLEAR) genes. In a clinical trial, Zevra found that Miplyffa plus miglustat stopped disease progression during 12 months of treatment, decreasing patients’ scores on an assessment of NPC symptom severity. Meanwhile, patients treated with miglustat alone experienced a progression in symptoms. The second approval was for IntraBio’s Aqneursa (levacetylleucine) in adults and children weighing at least 15 kg. According to the company, it is not clear what Aqneursa’s target is, but it may activate cerebral glucose metabolism in the cerebellum and thus boost cerebellar activity. A randomized, double-blinded and placebo-controlled crossover study found that during the 12-week period that patients were treated with Aqneursa, they showed better functional performance as measured by a score that assesses their gait, sitting, stance and speech. The drug was well-tolerated, with common side effects including vomiting, abdominal pain, difficulty swallowing and upper respiratory tract infections. The drug’s label includes a warning for embryo-fetal harm if used during pregnancy. The back-to-back NPC approvals highlighted the FDA’s commitment to supporting the development of innovative therapies for rare diseases, Janet Maynard, director of the agency’s Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, said in a statement . Cerebrotendinous Xanthomatosis Cerebrotendinous xanthomatosis (CTX) is a very rare metabolic disease, affecting just one in a million people globally . It is characterized by the inability to break down certain types of cholesterol and other lipids, leading to their toxic accumulation throughout the body, particularly in the brain and connective tissues. Patients with CTX suffer from neurological abnormalities in early adulthood, including seizures and problems with movement and speech. Just last week, CTX got its first approved drug with the FDA’s greenlight of Mirum Pharmaceuticals’ oral therapy Ctexli (chenodiol). CTX is caused by mutations in the CYP27A1 gene, which codes for an enzyme that breaks down cholesterol into bile acids, and Ctexli replenishes the body’s levels of bile acids. This reduces the build-up of the toxic metabolites that cause the disease. Mirum’s application for approval of the drug included data from the Phase III RESTORE study, a June 2024 readout of which showed the drug could lower bile alcohols “with high statistical significance,” the biotech said at the time. Ctexli’s benefit was 20-fold greater in magnitude than that of placebo. The most common adverse events associated with Ctexli include hypertension, muscle weakness and diarrhea, and its label includes precautions about potential liver toxicity.