Alpha-Mannosidosis

- Results presented from over a decade of treatment with velmanase alfa in alpha-mannosidosis – - Company also presents immunogenicity and tolerability data from pegunigalsidase alfa clinical trial program in Fabry disease – - Additional presentations provide new insights on prevalence, diagnosis, and progression of these rare lysosomal storage disorders – BOSTON, Feb. 8, 2024 /PRNewswire/ -- Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people living with rare diseases, today announced the presentation of long-term data from up to 12 years of treatment with velmanase alfa in patients with alpha-mannosidosis (AM). The company also announced the presentation of immunogenicity and tolerability data from its pegunigalsidase alfa clinical trial program in Fabry disease, as well as analyses of the prevalence, diagnosis, and progression of these rare lysosomal storage disorders. The data are being presented during the 20th Annual WORLDSymposium™ Research Meeting that is being held February 4-9, 2024, in San Diego, California. "This year's WORLDSymposium marks a significant moment for people living with rare lysosomal storage disorders including alpha-mannosidosis and Fabry disease, and their healthcare teams including clinicians and nurses, who now have access to recently approved treatment options and an important opportunity to understand the impact of these therapies and the barriers that must be addressed to improve diagnosis and disease management," said Giacomo Chiesi, head of Chiesi Global Rare Diseases. "Our company is driven by a commitment to rare disease communities around the world and we are taking full advantage of this conference to share our extensive clinical research in AM, which now spans more than a decade, and in Fabry disease, where we are continuing to evaluate data from our comprehensive development program. We are also emphasizing the importance of the caregiver and patient voice, reporting results from a range of surveys and analyses, hosting symposia, and presenting a special film screening that will help healthcare professionals identify and treat people in these communities in the years ahead." Results from long-term treatment with velmanase alfa in AM In an oral session, Prof. Nathalie Guffon, M.D., Reference Centre of inherited metabolic disease in Femme Mère Enfant Hospital, Hospices Civils of Lyon, France, is presenting results of an analysis that evaluated long‑term efficacy of up to 12 years of treatment with velmanase alfa, which is the first and only enzyme replacement therapy (ERT) available for people with AM. Pooled analyses demonstrate tolerability of pegunigalsidase alfa in Fabry disease and low incidence of de novo anti-drug antibodies Several poster presentations are highlighting immunogenicity and tolerability data from the pegunigalsidase alfa clinical trial program in Fabry disease. John Bernat, M.D., Ph.D., Medical Director of the Iowa Lysosomal Storage Disorders Center, is presenting a poster describing characteristics of anti-drug antibodies (ADAs) reacting with pegunigalsidase alfa, and the patients who develop ADAs, using data from an integrated clinical trial dataset. The analysis includes 108 patients, 27 (25%) of whom were ADA+ before receiving their first dose of pegunigalsidase alfa. There was a low incidence of de novo ADAs (n=17) occurring predominantly in the first year of treatment with pegunigalsidase alfa. Neutralizing antibodies were detected in <25% of patients with de novo ADAs versus in almost all patients who were ADA+ at baseline. In separate poster presentations, Derralynn Hughes, M.D., Professor of Experimental Haematology at the University College London, and Ankit Mehta, M.D., FASN, Baylor University Medical Center, are sharing results from analyses of the tolerability of pegunigalsidase alfa across the clinical program per dosing regimen and prior enzyme replacement therapy (ERT) experience, respectively. Dr. Hughes found that less than a third of patients receiving pegunigalsidase alfa experienced infusion related reactions (IRRs), most of which occurred from the start of the infusion until up to two hours after its end among patients with pre-existing or de novo ADAs. The frequency of IRRs decreased over time and in parallel with a decrease in premedication use among those switching from prior ERT. Dr. Mehta found that IRRs from the start of the infusion until up to two hours after its end occurred in about a quarter of either ERT-naive or ERT-switch patients following treatment with pegunigalsidase alfa. Most of these IRRs were mild to moderate in severity and occurred predominantly in the first year after initiating the therapy. Surveys and epidemiological analyses shed new light on the prevalence, diagnosis, and progression of AM and Fabry disease Chiesi Global Rare Diseases is announcing five additional presentations focused on improving awareness and understanding of the patient experience with rare lysosomal storage disorders including AM and Fabry disease. In an oral presentation, Stuart Gaffney, M.D., Medical Manager, Chiesi Global Rare Diseases, is sharing results from interviews and surveys with Fabry disease patients (n=20), nurses, and clinicians to understand the diagnostic journey and identify unmet medical education needs of UK primary and specialty healthcare professionals. The most common first symptom of Fabry disease was neuropathic pain, and the first severe indication for many patients was chest pain and general heart complaints. Cardiologists were the main specialists identifying Fabry disease, and 55% (11/20) of patients saw a cardiologist who was the first to suspect Fabry disease was the cause of their symptoms. In a poster presentation, Patricia Dorling, Head of Global Health Economics and Outcome Research (GHEOR), Chiesi USA, is reporting results from a study that analyzed data from the Adelphi Fabry Disease Specific Programme™ (DSP), a national representative online survey of physicians treating patients with a confirmed diagnosis of Fabry disease in the United States. Results demonstrate that the burden of complications and use of medical services (HCRU) is substantial with 76% of patients undergoing routine clinical examinations over two years and 19% of patients being hospitalized due to Fabry disease over one year. In a poster presentation, Khashayar Azimpour, M.D., Ph.D., Director, Global Health Economics and Outcome Research (GHEOR), Chiesi USA, is reporting results from a study aimed to estimate diagnosed Fabry disease prevalence and treatment rates in the U.S. via a retrospective cohort analysis. The 2021 diagnosed prevalence was 5,462 people, and 3,747 of those people with Fabry disease had received treatment. The findings highlight potentially higher gender disparities in treatment than previous estimates, signifying greater need for treatment in females. In a poster presentation, Nicole Muschol, M.D., International Center for Lysosomal Disorders (ICLD) at the University Medical Center Hamburg-Eppendorf in Germany, is reporting results from a Delphi study that generated 60 internationally applicable best practice recommendations for the initial assessment of newly diagnosed AM patients and their routine follow-up and integrated care coordination. In a poster presentation, Prof. Guffon is highlighting results from an international caregiver and patient survey designed to assess the impact of AM on patients' functional ability and quality of life. Results confirm that an important treatment goal is stabilizing and slowing disease progression. Untreated patients reported deterioration at a functional, pain and quality of life level, while patients treated with ERT or allogeneic haematopoietic stem cell transplantation reported less decline in walking ability and improved ability to self-care. Chiesi Global Rare Diseases is sponsoring three satellite symposia during WORLDSymposium to review perspectives on the management of Fabry disease and AM including insights from clinicians, caregivers, and patients. The company is also presenting a special screening of "Rare Land," a film focused on AM, with an expert panel featuring Robert Hopkin, M.D., Clinical Geneticist at Cincinnati Children's Hospital Medical Center and Martin Magner, M.D., Ph.D., Department of Paediatrics and Hereditary Metabolic Disorders of the General University Hospital of Prague. In addition, the company is presenting during the Industry Expert Theater session and is participating in the Patient Voice and Preference meeting. Indication and Important Safety Information for Elfabrio® (pegunigalsidase alfa-iwxj) Indication Elfabrio® (pegunigalsidase alfa-iwxj) is indicated for the treatment of adults with confirmed Fabry disease. Important Safety Information Prior to Elfabrio administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Inform patients and caregivers of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions (IARs), and instruct them to seek medical care immediately if such symptoms occur. If a severe hypersensitivity reaction (including anaphylaxis) or severe IAR occurs, immediately discontinue Elfabrio administration and initiate appropriate medical treatment. If a mild to moderate hypersensitivity reaction or IAR occurs, consider slowing the infusion rate or temporarily withholding the dose. In clinical trials, 20 (14%) Elfabrio-treated patients experienced hypersensitivity reactions. Four Elfabrio-treated patients (3%) experienced anaphylaxis reactions that occurred within 5 to 40 minutes of the start of the initial infusion. The signs and symptoms of hypersensitivity reactions and anaphylaxis included headache, nausea, vomiting, throat tightness, facial and oral edema, truncal rash, tachycardia, hypotension, rigors, urticaria, intense pruritus, moderate upper airway obstructions, macroglossia, and mild lip edema. In clinical trials, 41 (29%) Elfabrio-treated patients experienced one or more infusion-associated reactions, including hypersensitivity, nausea, chills, pruritus, rash, chest pain, dizziness, vomiting, asthenia, pain, sneezing, dyspnea, nasal congestion, throat irritation, abdominal pain, erythema, diarrhea, burning sensation, neuralgia, headache, paresthesia, tremor, agitation, increased body temperature, flushing, bradycardia, myalgia, hypertension, and hypotension. A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitor serum creatinine and urinary protein-to-creatinine ratio. If glomerulonephritis is suspected, discontinue treatment until a diagnostic evaluation can be conducted. When switching to Elfabrio from a prior enzyme replacement therapy, the risk of hypersensitivity reactions and infusion-associated reactions may be increased in certain patients with pre-existing anti-drug antibodies (ADAs). Consider monitoring IgG and IgE ADAs and clinical or pharmacodynamic response (eg, plasma lyso-Gb3 levels). The most common adverse reactions (≥15%) were infusion-associated reactions, nasopharyngitis, headache, diarrhea, fatigue, nausea, back pain, pain in extremity, and sinusitis. Please see Full Prescribing Information for Elfabrio. Indication and Important Safety Information for Lamzede® (velmanase alfa-tycv) Indication Lamzede® (velmanase alfa-tycv) is indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients. Important Safety Information Considerations Due to Hypersensitivity Reactions and/or Infusion-Associated Reactions (IARs) Prior to Lamzede administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Inform patients and caregivers of the signs and symptoms of hypersensitivity reactions and IARs and instruct them to seek medical care immediately if such symptoms occur. If a severe hypersensitivity reaction (including anaphylaxis) or severe IAR occurs, immediately discontinue Lamzede administration and initiate appropriate medical treatment. In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, consider temporarily holding the infusion for 15 to 30 minutes, slowing the infusion rate to 25% to 50% of the recommended rate, and initiating appropriate medical treatment. Hypersensitivity Reactions Including Anaphylaxis Anaphylaxis and severe hypersensitivity signs and symptoms included cyanosis, hypotension, emesis, urticaria, erythema, facial swelling, pyrexia, and tremor. Infusion-Associated Reactions (IARs) The most frequent symptoms of IARs that occurred in >10% of the population were pyrexia, chills, erythema, vomiting, cough, urticaria, rash, and conjunctivitis. Females of Reproductive Potential Advise females of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if Lamzede is discontinued. For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with Lamzede. Embryo-Fetal Toxicity Based on findings from animal reproduction studies, Lamzede may cause embryo-fetal harm when administered to a pregnant female. Common Adverse Reactions The most common adverse reactions (incidence >20%) are hypersensitivity reactions including anaphylaxis, nasopharyngitis, pyrexia, headache, and arthralgia. Please see Full Prescribing Information for Lamzede. About Chiesi Global Rare Diseases Chiesi Global Rare Diseases is a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people affected by rare diseases. As a family business, Chiesi Group strives to create a world where it is common to have a therapy for all diseases and acts as a force for good, for society and the planet. The goal of the Global Rare Diseases unit is to ensure equal access so as many people as possible can experience their most fulfilling life. The unit collaborates with the rare disease community around the globe to bring voice to underserved people in the health care system. For more information visit . About Chiesi Group Chiesi is an international, research-focused biopharmaceuticals group that develops and markets innovative therapeutic solutions in respiratory health, rare diseases, and specialty care. The company's mission is to improve people's quality of life and act responsibly towards both the community and the environment. By changing its legal status to a Benefit Corporation in Italy, the US, and France, Chiesi's commitment to create shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, we're part of a global community of businesses that meet high standards of social and environmental impact. The company aims to reach Net-Zero greenhouse gases (GHG) emissions by 2035. With over 85 years of experience, Chiesi is headquartered in Parma (Italy), operates in 31 countries, and counts more than 6,500 employees. The Group's research and development centre in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden. For further information please visit . Chiesi Group Media Contacts Chiara Travagin Rare Communication Manager Tel: +39 348 8818985 Email: [email protected] Alessio Pappagallo Press Office Manager Tel: +39 339 5897483 Email: [email protected] Adam Daley Berry & Company Public Relations Tel: +1 212 253 8881 Email: [email protected] PP-MULTI-0288 V2.0 SOURCE Chiesi Global Rare Diseases

The FDA's approval of rare skin disease drug Filsuvez gives Chiesi Global Rare Diseases its third nod for a new drug from the U.S. regulator this year. Seven months after Krystal Biotech became the first company to gain FDA approval to treat the rare, devastating skin disease epidermolysis bullosa (EB), Chiesi Farmaceutici has followed suit. On Tuesday, the U.S. regulator gave a thumbs up to Chiesi’s Filsuvez (birch triterpenes) to treat both junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB) in patients 6 months and older. While Krystal’s topical gene therapy Vyjuvek was endorsed by the FDA in May for DEB, Filsuvez becomes the first FDA-sanctioned treatment for both JEB and DEB. The topical gel treats the wounds associated with EB, a genetic, connective tissue disease that causes the skin to become fragile. Even the slightest friction can tear the skin and cause blisters. EB can be life-threatening as patients are at risk of developing aggressive squamous cell carcinomas and infections. The active ingredient in Filsuvez, which is found in birch trees, accelerates healing and reduces the size of the wound. “The FDA’s decision to approve Filsuvez provides those living with EB a safe and effective treatment option for the most prominent and difficult symptom of EB, open wounds that may not heal,” said Brett Kopelan, the executive director of debra of America, a non-profit that raises money and supports those with EB. This is the third FDA approval this year for Chiesi Global Rare Diseases, which was established in 2020 as one three business units of the family-owned Chiesi Group. The other FDA nods came for enzyme replacement therapies Elfabrio, which treats the neurological disorder Fabry disease, and Lamzede for the genetic condition alpha-mannosidosis, which causes a buildup of sugars in the organs. The FDA green light for Filsuvez was based on the phase 3 EASE trial, which showed significant increase in healing and wound closure compared to patients who received an active control gel, measured at 45 days. Filsuvez was rejected by the FDA in February of 2022, with the regulator asking for more efficacy data. Four months later, Europe endorsed the treatment for DEB and JEB. The drug was owned then by Amryt Pharma of Ireland. In January of this year, Chiesi acquired Amryt Pharma in a $1.25 billion buyout. Along with the purchase came three approved rare disease treatments—Juxtapid, for hypercholerterolemia, Myalept, for lipodystrophy, and Mycapssa, for acromegaly. With its launch of Filsuvez, Chiesi will face formidable competition. Krystal Biotech's launch of Vyvuvek has been so promising that ISI Evercore bumped up its projected 2024 sales of the gene therapy to $273 million. 

Americans can’t afford their medications. About 25% leave prescriptions unfilled, split pills, or skip doses. Seniors face challenges covering non-Medicare services, including prescriptions. Even those with commercial health insurance are not immune. One-third of insured adults worry about affording their premiums, and 44% must meet increasingly high deductibles before insurance even kicks in. As a result, 41% of adults carry substantial medical debt. At the same time, FDA approvals for therapeutics targeting rare diseases are on the rise, including those for cancer, Alzheimer’s, and many previously untreatable diseases. In fact, 54% of 2022’s novel drug approvals targeted rare diseases. They encompass groundbreaking therapies like the first acid sphingomyelinase deficiency treatment, a prurigo nodularis remedy, and an obstructive hypertrophic cardiomyopathy therapy. In 2023, the first enzyme replacement therapy for non-neurological alpha-mannosidosis effects gained early approval. Breakthroughs, though welcome, are staggeringly expensive. In fact, Hemgenix, a new treatment for hemophilia, is officially the most expensive drug in the world at $3.5 million annually, followed by Zynteglo for thalassemia at $2.8 million per dose, and Zokinvy for Hutchinson-Gilford progeria syndrome at $1.7 million. Even medications for more common conditions can be cripplingly expensive. Over the past decade, median annual prices for disease-modifying therapies for multiple sclerosis have surged by nearly $34,000, reaching a median price of almost $94,000. Some have witnessed price hikes of over 200%, with nine now exceeding $100,000. Rheumatoid arthritis patients face medical costs that average $12,500 annually, and over $36,000 for those prescribed a biologic. Those biologic disease-modifying antirheumatic drugs range from $25,000–$40,000 a year. Leqvio, a semiannual cholesterol-lowering injection, costs between $3,191 and $6,782 per dose. In addition to financial challenges, patients with rare diseases encounter difficulties in accessing essential clinical services despite availability, and that combined with pressure from payers to lower care delivery costs has driven the rapid growth of ambulatory infusion centers. Ambulatory infusion centers are more accessible than hospitals because they are scattered geographically, unlike single-location hospitals in urban centers. Infusion center settings allow medical professionals to closely monitor patients, improving adherence for complex conditions requiring infusions. Research indicates a 79% adherence rate for office-based infusions, compared to 74% at hospitals and 64% at home. Home or hospital-infused patients averaged four to five specialist visits, while infusion center-infused patients averaged 14, leading to better disease management and outcomes. Administering specialty drugs through ambulatory infusion centers offers substantial cost savings. These settings can cut specialty medication administration expenses by 50% for major HCPS codes, which constitute a significant portion of specialty medical spending, reducing costs by $16,000 to $37,000 per privately insured patient annually for major conditions. Those dealing with rare, complex, and chronic conditions need a new care model to ensure that they have access to lifesaving, transformative medications regardless of their insurance coverage, or lack of it. Ambulatory infusion centers are increasingly providing that much-needed access, support and, increasingly, financial assistance. To offer a differentiated patient financial experience, some infusion centers have partnered with software companies to further enhance their service offerings. Such technology platforms utilize data and predictive analytics to flag patients in need and match them with relevant financial resources, including drug manufacturer copay assistance programs, foundation grants, government assistance, and more. These companies can streamline and automate what is often a manual, labor-intensive process, empowering staff to reach more patients and maximize cost-saving opportunities. By improving affordability, collaborations between ambulatory infusion centers and comprehensive software solution providers who automate financial navigation expand access to lifesaving drugs and increase the likelihood of treatment adherence and positive outcomes. Progress comes at a price. Developing new medications and treatments for rare diseases takes years of research and deep pockets, but the human costs for real patients and their families, healthcare providers, and caretakers must be factored in as well. Healthcare has traditionally been built around the convenience of the provider and not the patient. Worse, it tends to treat all patients the same regardless of the condition they are trying to manage. If we want to improve compliance, we have to make access, support, and most importantly financial assistance a priority.