Bromocriptine Mesylate

• Results presented from a large, pooled database from three Phase 3 clinical trials evaluating MYCAPSSA (octreotide) for the treatment of people living with acromegaly • Additional presentations provide insights into the validation of the Lipodystrophy Severity Scoring tool and the Chiesi Management of Acromegaly (MACRO) registry BOSTON, June 14, 2024 (GLOBE NEWSWIRE) -- Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people living with rare diseases, announced updates from their rare endocrine disease portfolio with two late-breaking poster presentations and one oral presentation during the Endocrine Society’s ENDO 2024 Meeting that was held June 1-4, 2024, in Boston, Massachusetts. Presentations included a post hoc analysis of three Phase 3 clinical trials (CH-ACM-01, OPTIMAL, MPOWERED) studying MYCAPSSA (octreotide) as well as real-world MYCAPSSA use data from the Chiesi Management of Acromegaly (MACRO) registry and presentation of the Lipodystrophy Severity Scoring tool designed to assess the disease burden of lipodystrophy. "We're thrilled to support this community of people living with burdensome rare endocrine diseases through the innovation of new resources and validated medicines to aid in disease management," said Giacomo Chiesi, Head of Chiesi Global Rare Diseases. "As we approach the four-year anniversary of MYCAPSSA being on the market later this month, our commitment remains steadfast to commercializing solutions for the acromegaly and lipodystrophy patient communities.” Oral PresentationTitle: Biochemical Response, Symptom Control, and Safety of Oral Octreotide Capsules Treatment in Acromegaly: A Post Hoc Analysis of a Large Pooled Database from Three Phase 3 Clinical Trials2Key Highlights: MYCAPSSA demonstrated a 72% response rate in patients entering the studies with IGF-I values of ≤ 1x the upper limit of normal. A patient’s prior dose level of injectable medication did not significantly impact response rates.In this post-hoc analysis, symptom improvement was notable with significant reductions in joint pain (36% to 22%) and swelling (15% to 10%) in patients responding to MYCAPSSA. Median decrease of one symptom per patient and a mean decrease of 0.8 in Acromegaly Index of Severity (AIS) further underscored symptom improvement.Safety analysis revealed gastrointestinal issues as the most common adverse events with a median duration and time to onset of roughly two weeks for the first occurrence and a low rate of discontinuation. Late-Breaker Poster PresentationsTitle: Real-world Biochemical And Symptoms Outcomes With Oral Octreotide: Management Of Acromegaly (MACRO) Registry Experience3Key Highlights: Of the 230 patients participating in Chiesi Management of Acromegaly (MACRO) registry, 32 (14%) received MYCAPSSA at baseline, with an additional 26 (11%) initiating post-baseline. Common reasons for initiation included patient preference and lack of symptom or biochemical control.The mean time on OOC was 19.7 months, with the majority receiving treatment for at least 6 months. Most patients remained well-controlled biochemically and symptomatically, with 87% biochemically controlled and 71% symptomatically controlled at the last follow-up.The discontinuation rate was 33% and in cases attributed to a lack of biochemical or symptom control, dose titration to 80mg/day was not implemented in many cases.Overall, OOC demonstrated efficacy in maintaining or achieving biochemical control with the majority of newly-initiated patients reporting well-controlled symptoms. Title: Lipodystrophy Severity Score: Validation Of A Tool To Assess Disease Burden In Lipodystrophy4Key Highlights: The lipodystrophy severity score (LDS) is a validated tool that captures severity in patients with diverse manifestations of lipodystrophy. The LDS allows comparisons among patient groups and changes within patients over time.The LDS is a tool designed to quantify the diverse complications of lipodystrophy, a group of rare, potentially life-threatening disorders that affect how the body accumulates and stores fat.The LDSs showed high reliability and strong correlation with the Clinical Global Impression (CGI) of severity, effectively capturing the severity of lipodystrophy and changes over time. This tool is intended to compare patient groups, and monitor individual progress with future analysis involving in real-world data sets.Development into an online platform enhances functionality – a versatile and valuable resource for the lipodystrophy community.Future work will assess the LDS using real-world datasets. MYCAPSSA IMPORTANT SAFETY INFORAMATION INDICATION AND USAGE MYCAPSSA (octreotide) delayed-release capsules, for oral use, is a somatostatin analog indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide. CONTRAINDICATIONS Hypersensitivity to octreotide or any of the components of MYCAPSSA. Anaphylactoid reactions, including anaphylactic shock, have been reported in patients receiving octreotide. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS MYCAPSSA can cause problems with the gallbladder. Monitor patients periodically. Discontinue if complications of cholelithiasis are suspected. Blood sugar, thyroid levels, and vitamin B12 levels should be monitored and treated accordingly. Bradycardia, arrhythmia, or conduction abnormalities may occur. Treatment with drugs that have bradycardia effects may need to be adjusted. ADVERSE REACTIONS The most common adverse reactions (incidence >10%) are nausea, diarrhea, headache, arthralgia, asthenia, hyperhidrosis, peripheral swelling, blood glucose increased, vomiting, abdominal discomfort, dyspepsia, sinusitis, and osteoarthritis. DRUG INTERACTIONS The following drugs require monitoring and possible dose adjustment when used with MYCAPSSA: cyclosporine, insulin, antidiabetic drugs, calcium channel blockers, beta blockers, lisinopril, digoxin, bromocriptine, and drugs mainly metabolized by CYP3A4. Counsel women taking an oral contraceptive to use an alternative non-hormonal method of contraception or a back-up method when taking MYCAPSSA. Patients taking proton pump inhibitors, H2-receptor antagonists, or antacids concomitantly with MYCAPSSA may require increased dosages of MYCAPSSA. PREGNANCY Advise premenopausal females of the potential for an unintended pregnancy. Please contact Chiesi Farmaceutici S.p.A. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. About AcromegalyAcromegaly typically develops when a benign tumor of the pituitary gland produces too much growth hormone, ultimately leading to significant health problems. Common features of acromegaly are facial changes, intense headaches, joint pain, impaired vision, and enlargement of the hands, feet, tongue, and internal organs. Serious health conditions associated with the progression of acromegaly include type 2 diabetes, hypertension, respiratory disorders, and cardiac and cerebrovascular disease. Acromegaly affects over 25,000 people in the United States alone with roughly 8,000 being treated with injectable somatostatin receptor ligands (iSRLs). A significant percentage of these people experience burdens associated with receiving iSRLs including prolonged injection-related pain and poorly-controlled symptoms. About LipodystrophyLipodystrophy syndromes are a heterogeneous group of rare, potentially life-threatening disorders that affect how the body accumulates and stores fat. These syndromes are categorized into two main forms: generalized lipodystrophy, characterized by the near-complete absence or progressive loss of fat (adipose) tissue, and partial lipodystrophy, where the tissue loss is more limited, typically impacting areas like limbs or upper body. Lipodystrophy is also categorized by etiology with inherited and acquired forms1. About Chiesi Global Rare DiseasesChiesi 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 www.chiesirarediseases.com. About Chiesi GroupChiesi 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 www.chiesi.com Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004 Mar 18;350(12):1220-34. Doi: 10.1056/NEJMra025261. PMID: 15028826.Fleseriu M, et al. Biochemical Response, Symptom Control, and Safety of Oral Octreotide Capsules Treatment in Acromegaly: A Post Hoc Analysis of a Large Pooled Database from Three Phase 3 Clinical Trials. Presented at: Endocrine Society’s ENDO 2024 Meeting; June 1-4, 2024; Boston, Massachusetts.Yuen K, et al. Real-world Biochemical And Symptoms Outcomes With Oral Octreotide: Management Of Acromegaly (MACRO) Registry Experience. Presented at: Endocrine Society’s ENDO 2024 Meeting; June 1-4, 2024; Boston, Massachusetts.Brown R, et al. Lipodystrophy Severity Score: Validation Of A Tool To Assess Disease Burden In Lipodystrophy. Presented at: Endocrine Society’s ENDO 2024 Meeting; June 1-4, 2024; Boston, Massachusetts. Chiesi Group Media ContactChiara TravaginRare Communication ManagerTel: +39 348 8818985Email c.travagin@chiesi.com Sky Striar LifeSci CommunicationsTel: 617-797-6672Email sstriar@lifescicomms.com

New research points to a potential approach to reducing the risk of diabetes associated with widely prescribed antipsychotic medications. The study presents early evidence in support of co-administering antipsychotic medications that block dopamine receptors in the brain alongside drugs that stop antipsychotics from blocking those same receptors in the pancreas. This approach could limit metabolic side effects, including impaired control over blood sugar, or dysglycemia. New University of Pittsburgh research points to a potential approach to reducing the risk of diabetes associated with widely prescribed antipsychotic medications. The study presents early evidence in support of co-administering antipsychotic medications that block dopamine receptors in the brain alongside drugs that stop antipsychotics from blocking those same receptors in the pancreas. This approach, published today in Diabetes, could limit metabolic side effects, including impaired control over blood sugar, or dysglycemia. This research may also explain why weight control medications, including new neuropeptide drugs Wegovy and Ozempic, may not be as effective as hoped in controlling dysglycemia caused by antipsychotic drugs. Patients who are experiencing the weight gain associated with antipsychotic medications might be tempted to take these new drugs to control satiety -- but they may miss an important underlying cause of the drug-induced deglycation. "Antipsychotic medications don't just stop working below the neck," said senior author Zachary Freyberg, M.D., Ph.D., associate professor of psychiatry and cell biology at Pitt's School of Medicine. "Maintaining glucose metabolism requires the brain to be in constant communication with the rest of the body, and vice versa. Next-generation antipsychotic drugs can be modified as a new strategy to control dysglycemia and diabetes." Most prescription antipsychotic medications work by blocking the class of brain receptors that respond to a neurotransmitter called dopamine -- a cornerstone molecule of the brain's reward system and brain-directed movement control. However, the subtype of dopamine receptors that respond to antipsychotic medications, called dopamine D2 receptors, are not exclusive to the brain. As Freyberg's earlier research has shown, antipsychotic medications also block D2 receptors in the pancreas. Freyberg's dogma-breaking discovery highlighted that pancreatic dopamine plays a key role in controlling blood sugar by interacting with D2 receptors on the surface of pancreatic cells that control production and secretion of hormones insulin and glucagon. When the fragile balance between glucose-raising and -lowering hormones is destabilized by antipsychotic medications, dysglycemia and diabetes may follow. However, peripheral dopamine signaling can be harnessed for therapeutic good. In collaboration with researchers at the National Institutes of Health's National Institute on Drug Abuse (NIH NIDA), the team created a molecule that can limit antipsychotic drugs from blocking D2 receptors in organs like the pancreas, but not in the brain. This molecule, called bromocriptine methiodide, or BrMel, is structurally similar to bromocriptine -- an FDA-approved drug to treat type 2 diabetes -- but has a modification that makes it less likely to pass through the brain-blood barrier if administered systemically, therefore limiting its activity to the periphery. Early studies in mice suggest that dopamine's effects on glucose metabolism require communication between the brain and the peripheral organs including the pancreas. Experiments have shown that, unlike systemically administered bromocriptine that improves the glucose pro insulin-resistant mice, peripherally-limited BrMeI, or bromocriptine delivered directly to the brain, failed to show improvements. Drugs like BrMeI that can stop antipsychotic medications from acting on peripheral targets may therefore be useful in preventing, or even reversing, dysglycemia. Freyberg and his collaborators at Pitt are in the early stages of a safety clinical trial to ensure that the therapeutic effects of antipsychotic drugs are preserved when these psychiatric medications are administered in tandem with bromocriptine since it is already FDA approved. They hope to launch a bigger trial to test the efficacy of BrMel and similar molecules for limiting dysglycemia in the next several years. "The fact that both the brain and the body are required to maintain stable glycemic control provides a novel dimension in understanding neuropsychiatry and begins to integrate disparate pieces of knowledge about different organ systems into a coherent whole," said Freyberg. "The majority of psychiatric medications are prescribed by general practitioners and not psychiatrists," he added. "We hope that our research builds awareness about the importance of communication between the brain and the rest of the body in maintaining physiological functions and reminds clinicians that they should also consider that drugs designed to act on targets in the brain, like psychiatric medications, may also have significant actions outside of the brain when making prescription recommendations." Other authors of this research are Zachary Farino, M.S., Despoina Aslanoglou, Ph.D., and José Mantilla-Rivas, M.D., all of Pitt; Alessandro Bonifazi, Ph.D., Michael Ellenberger, J.D., Comfort Boateng, Ph.D., and Amy Hauck Newman, Ph.D., all of NIDA; Rana Rais, Ph.D., and Barbara Slusher, Ph.D., both of Johns Hopkins University; Sandra Pereira, Ph.D., and Margaret Hahn, M.D., Ph.D., both of the University of Toronto; Amy Eshleman, Ph.D., and Aaron Janowsky, Ph.D., both of the Oregon Health & Science University; and Gary Schwartz, Ph.D., of Albert Einstein College of Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.