Craniopharyngioma

-- Supplemental cohort of 12 Japanese patients to be added to global Phase 3 hypothalamic obesity trial, with dosing expected to begin in third quarter of 2024 -- -- Significant unmet need with 5,000 to 8,000 patients with hypothalamic obesity estimated to be living in Japan -- BOSTON, Feb. 22, 2024 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients and their families living with rare neuroendocrine diseases, today announced plans to add a cohort of patients with hypothalamic obesity in Japan to its ongoing global Phase 3 clinical trial of setmelanotide, with dosing expected to begin in the third quarter of 2024. “Following constructive discussions with Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), we are pleased to have developed a clear and efficient plan to support the potential approval of setmelanotide for hypothalamic obesity in Japan,” said David Meeker, M.D., Chair, President and Chief Executive Officer of Rhythm. “With data showing a higher per-capita incidence and prevalence of patients with hypothalamic obesity in Japan compared to the United States and Europe and no approved therapeutic options, there is a major unmet need for a therapy to treat the rapid onset of severe obesity and hyperphagia of hypothalamic obesity.” Rhythm estimates that there are approximately 5,000 to 8,000 patients in Japan with hypothalamic obesity, a rare form of obesity that occurs following damage to the hypothalamic region of the brain, which includes the melanocortin-4 receptor (MC4R) pathway and is responsible for controlling physiological functions such as hunger and weight regulation. The condition most frequently follows the growth and surgical removal or other treatment of craniopharyngioma, astrocytoma, or other rare brain tumors. These individuals often experience rapid weight gain, a reduction in energy expenditure, and an increase in hunger leading to severe obesity within six to 12 months following the hypothalamic lesions. The Company and Japan’s PMDA agreed to add a cohort of 12 Japanese patients to the ongoing trial and, pending completion of the trial, to use these data as part of the Company’s registration package to seek approval from Japan’s Ministry of Health, Labor and Welfare. In addition to efficacy data, Rhythm will collect and submit pharmacokinetics (PK) data from Japanese patients, expediting the typical pathway of collecting such data from an earlier-stage trial in Japanese subjects. Rhythm also announced today that it completed enrollment in the pivotal, 120-patient cohort in its global Phase 3 trial of setmelanotide in hypothalamic obesity with patients, aged 4 years or older with hypothalamic obesity randomized 2:1 to setmelanotide therapy or placebo for a total of 60 weeks, including up to eight weeks for dose titration. As agreed to with both the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), Rhythm’s regulatory submissions would be based on data from this cohort. The additional 12-patient Japanese cohort will not affect timing for regulatory submissions in the United States or Europe. The Company remains on track to obtain top-line study results in the first half of 2025. About Rhythm PharmaceuticalsRhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, is approved by the U.S. Food and Drug Administration (FDA) for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as RM-718 and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. Setmelanotide Indication In the United States, setmelanotide is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to POMC, PCSK1 or LEPR deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1 or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS) or BBS. In the European Union, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. In Europe, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Limitations of Use Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benignOther types of obesity not related to POMC, PCSK1 or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity. Contraindication Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. WARNINGS AND PRECAUTIONS Skin Pigmentation and Darkening of Pre-Existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred because of its pharmacologic effect. Full body skin examinations prior to initiation and periodically during treatment should be conducted to monitor pre-existing and new pigmentary lesions. Heart rate and blood pressure monitoring: In Europe, heart rate and blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients treated with setmelanotide. Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Patients who have an erection lasting longer than 4 hours should seek emergency medical attention. Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Patients should be monitored for new onset or worsening depression or suicidal thoughts or behaviors. Consideration should be given to discontinuing setmelanotide if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur. Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue setmelanotide. Pediatric Population: The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated. In Europe, the prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves. Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs. ADVERSE REACTIONS Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection. USE IN SPECIFIC POPULATIONS Lactation: Not recommended when breastfeeding.To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See section 4.8 of the Summary of Product Characteristics for information on reporting suspected adverse reactions in Europe. Please see the full Prescribing Information for additional Important Safety Information. Forward-looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical design or progress, potential regulatory submissions, approvals and timing thereof, including our Phase 3 trial of setmelanotide for patients with hypothalamic obesity in Japan, the United States or in Europe, the potential benefits of setmelanotide for patients with hypothalamic obesity, and our business strategy and plans, including regarding commercialization of IMCIVREE. Statements using word such as “expect”, “anticipate”, “believe”, “may”, “will” and similar terms are also forward-looking statements. Such statements are subject to numerous risks and uncertainties, including, but not limited to, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the impact of competition, the ability to achieve or obtain necessary regulatory approvals, risks associated with data analysis and reporting, our ability to successfully commercialize setmelanotide, our liquidity and expenses, our ability to retain our key employees and consultants, and to attract, retain and motivate qualified personnel, and general economic conditions, and the other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the three months ended September 30, 2023 and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise. Corporate Contact:David ConnollyHead of Investor Relations and Corporate CommunicationsRhythm Pharmaceuticals, Inc.857-264-4280dconnolly@rhythmtx.com Media Contact:Adam DaleyBerry & Company Public Relations212-253-8881adaley@berrypr.com

香港 2023年12月2日 /美通社/ -- 养和医疗集团（养和）今天宣布养和质子治疗中心（中心）正式开幕。位于筲箕湾阿公岩养和东区医疗中心内的质子治疗中心设有两间设备先进的质子治疗室，以及全港首部质子治疗系统，包括两座半旋转机座、一部同步加速器以及尖端的光束传输系统。该系统以垂直层叠方式巧妙布置，这种紧凑的装置设计，成为在有限空间内安装此庞然巨物的绝佳示范，可供类似香港这样人口稠密、土地资源短缺的城市作参考。 中心开幕典礼的主礼嘉宾 香港特别行政区政府医务卫生局局长卢宠茂教授 致辞时表示："我们十分乐见香港引入质子治疗，此治疗技术能为病人提供一个更高效且更低入侵性的治疗方案。香港特区政府近年一直致力在各方面推动香港医疗科技发展，例如开展大规模基因组定序计划以推广基因组医学，以及引入关于先进疗法产品的恒常机制。在最近的行政长官施政报告中亦提到，特区政府会继续与社会各界不同持分者通力合作，将香港发展成一个医疗创新枢纽。" 养和医疗集团行政总裁暨养和医院院长李维达医生 表示："将质子治疗带进香港是一个长达十年并极具挑战的旅程，我们感谢株式会社日立制作所协助引入质子治疗系统，亦庆幸能请到妙佑医疗国际亚利桑那州院区的国际专家监督养和质子治疗的初步临床应用，并为我们的临床肿瘤科专科医生及医学科学家设计训练课程。除质子治疗外，养和亦提供多元化的癌症管理服务，包括癌症遗传基因测试、诊断、复康以及辅导。未来数年，位于筲箕湾之养和东区医疗中心的住院服务、手术室和其他癌症治疗设施亦将会陆续投入服务。我们的目标是为癌症病人带来尖端的科技及治疗方式，我们亦致力提升病人体验，确保每位癌症病人能在其抗癌旅程中获得最充分的支援。" 养和医疗集团营运总监、养和医院董事李维文先生 指出："养和质子治疗中心的成立是18年来努力累积的成果。中心选址于坚固的花岗岩上，并由工业大厦改建成医疗用途，令整个建造过程变得相当艰巨，可说是养和至今最具挑战的工程项目之一。质子治疗是一项尖端的放射治疗技术，为配合质子治疗中心的营运，我们亦不断扩大专业的肿瘤科医疗团队，并邀请妙佑医疗国际亚利桑那州院区为他们提供相关专业训练，以确保高水准治疗质素。养和现时为全球首屈一指的医疗机构，具备最齐全之放射治疗设施，务求给予患者最适切的癌症治疗选择。适逢李树芬医学基金会成立60周年，养和质子治疗中心的启用亦秉承了其宗旨，将顶尖医疗科技带进香港。" 养和质子治疗中心由今年七月初步投入服务至今，已为约40名年龄介乎7岁至88岁的癌症病人提供治疗。这些个案涉及多种癌症类型，当中包括26宗乳癌、六宗儿童癌症，其余的个案有前列腺癌、头颈癌、胸腔癌症和颅脊髓癌。六宗儿童癌症个案均由香港儿童医院转介。这些儿童癌症个案包括神经母细胞瘤、恶性软组织肉瘤、上颌窦肉瘤、上颌窦癌及颅咽管瘤。 质子治疗被视为当前最先进用于治疗癌症的放射治疗技术。质子治疗与传统光子放射治疗最大的差异，是传统放射治疗的放射能量会穿透肿瘤组织，因此对肿瘤后方的正常组织也会造成伤害。相反，质子治疗高度精准，能锁定目标肿瘤，将辐射能量一次过集中释放到肿瘤位置，然后辐射能量便骤然停止并消散，这种独特的物理现象称为"布拉格峰"。 进行质子治疗时，医疗团队须精确计算质子射线的深度及强度，以瞄准癌细胞。由于质子射线只聚焦照射癌细胞，对肿瘤附近其他健康组织和器官影响甚微，从而降低了因传统放射治疗引起的并发症及副作用的风险。这种创新的治疗方式尤其适用于治疗头颈癌、脑癌、肺癌、肝癌、乳癌、胰脏癌、前列腺癌和肉瘤等。 养和医院临床肿瘤科名誉顾问医生、临床肿瘤科专科医生罗振基医生 详细阐述了头颈癌案例中采用质子治疗的独特优势，他称："虽然传统放射治疗与质子治疗对肿瘤靶区的辐射剂量相若，两种方法都能杀死癌细胞；但质子治疗对周边健康组织及器官所释放的辐射剂量要少得多。这对于头颈癌和脑癌患者至关重要，因为质子治疗可减少对唾液腺、眼睛、耳朵、口腔或整个大脑的辐射剂量，其好处便很明显，可减少口干、听力受损、视力障碍、口腔疼痛、颞叶坏死和引致周边区域继发性恶性肿瘤等副作用，所有这些潜在的并发症都可能对患者生活质量造成长远的影响。" 养和医院临床肿瘤科名誉顾问医生、临床肿瘤科专科医生张天怡医生 认为质子治疗也是治疗乳癌的上佳方案。她指出："特别是肿瘤靠近心脏和肺部等重要器官，质子治疗可保护相关器官免受辐射影响，有助减低日后出现心血管疾病的机会。" 张天怡医生 还说明质子治疗对前列腺癌的好处。主要优点包括显著减少对膀胱、直肠、肠道等附近器官的辐射剂量。她表示："许多临床研究均显示质子治疗非常有效，而且副作用极少。 由于质子治疗能够缩短治疗时间以及减少治疗所需的次数，患者可以更快完成疗程。" 养和医院儿科名誉顾问医生、儿童血液及肿瘤科专科医生陈志峰教授 表示："在儿童癌病的个案中，质子治疗能在不影响临床疗效的情况下，减低对患者短期和长远的伤害。对于正值成长期的儿童来说，质子治疗还能减低许多因辐射诱发的不良影响，包括：损害认知功能、诱发发育障碍和内分泌的问题，以及日后发生继发性恶性肿瘤的可能性。" 养和医院临床肿瘤科名誉顾问医生、临床肿瘤科专科医生甘冠明医生 最近为数名儿童患者进行质子疗程。他解释质子治疗对患者的好处时说："儿童患者在治疗后的存活期一般较长，而且由于他们在发育阶段，更容易出现辐射引发的慢性疾病，以及日后出现继发性癌症或其他并发症的风险。以治疗脑癌为例，质子治疗能够减少脑部发育中重要结构所承受的辐射剂量，有研究显示使用质子治疗和传统光子治疗，儿童髓母细胞瘤患者的十年整体存活率相近，而质子治疗对神经认知、甲状腺功能等影响较少，十年间出现继发性癌症的机会亦较低。" 香港人口老龄化导致癌症发病率上升，约每四人便有一人在75岁前罹患癌症 [1] 。养和旨在为癌症患者提供全面的支援，并因应他们的病情需要，为他们提供更多元化的治疗方案。随着引入质子治疗系统，养和已成为全球拥有最齐全放射治疗设备的医疗机构之一。 养和医疗集团营运总监、养和医院董事李维文先生 表示："养和质子治疗中心落成启用，为香港癌症治疗和管理方面开创新篇章，也实现了我们锐意建设一个卓越的癌症中心之承诺。我们除了增添必要的硬件和基本设施外，我们专业的肿瘤科医疗团队亦不断壮大，包括临床肿瘤科专科医生、放射治疗师、医学物理学家、医学放射计量师、肿瘤专科护士等，以应对患者各类疾病状况，确保他们得到最适切的治疗。" 李维文先生 一直在幕后策划和促成质子治疗中心的筹建，他透露引进质子治疗系统的构思始于2008年。他形容该中心可算是全球数一数二最复杂的质子治疗建设项目，皆因其选址于坚固的花岗岩上，且建筑楼面空间有限，建造过程相当艰巨。他补充："为了掘出地底的花岗岩，以腾出空间在地库装设质子治疗系统的机座和治疗室，团队费尽心思和努力；加上过去数年的新冠疫情亦令日立的工程人员无法前来香港进行组装。尽管面对各种挑战，质子治疗系统成功于今年七月交付并初步启用，我们非常感谢日立工程团队不懈努力。看到这项长达十年的项目取得成果，我们感到无比兴奋和欣慰。此外，我们已进行了近百项关于磁力共振导航用于放射治疗及质子治疗的研究，并会继续探研这些技术应用在临床上的效用，务求不断优化这些治疗的模式，以提升临床治疗的成效，让患者在疗程和护理方面达到更好的效果。" 此外，养和在质子治疗的过程中，更运用最先进的磁力共振导航技术。在这方面，养和可堪称为国际医疗机构的先驱。 养和医疗集团医学物理部主管余兆基博士 解释，部分肿瘤位于会移动或改变形状的器官，如肺部或肝脏，磁力共振导航可以追踪肿瘤移动的位置和幅度，令医生能够根据器官的移动和变化相应地调整质子射束的深度和强度，有助确保质子射束准确地瞄准目标肿瘤范围，让肿瘤接受最多的辐射剂量，同时大大减低对健康组织的损害。 养和会继续与公营机构和本地大学医学院合作，利用这套先进的质子治疗系统进行临床治疗、医学培训和科学研究。随着临床应用经验和研究数据不断累积，养和冀逐步扩大质子治疗的应用范围，从而让更多癌症患者受惠和改善其治疗效果。中心全面运作后，预计每年可为400至600名癌症病人进行治疗。 [1] 医院管理局2021 年香港癌症统计概览 开幕典礼的主礼嘉宾包括香港特别行政区政府医务卫生局局长卢宠茂教授（左二）、养和医疗集团行政总裁暨养和医院院长李维达医生（右二）、养和医疗集团营运总监、养和医院董事李维文先生（左一），以及养和医疗集团首席医务总监暨养和医院副院长曹延洲医生（右一）。 (左起) 养和医院临床肿瘤科名誉顾问医生、临床肿瘤科专科医生罗振基医生;养和医院儿科名誉顾问医生、儿童血液及肿瘤科专科医生陈志峰教授;养和医疗集团营运总监、养和医院董事李维文先生;养和医院临床肿瘤科名誉顾问医生、临床肿瘤科专科医生甘冠明医生;养和医疗集团医学物理部主管余兆基博士; 养和医院临床肿瘤科名誉顾问医生、临床肿瘤科专科医生张天怡医生分享质子治疗的发展及其临床应用。 关于养和医疗集团 养和医疗集团于 2017 年 9 月 28 日正式启动，旗下成员分别有养和医院、养和医健、 养和东区医 疗中心及养和癌症中心。养和医疗集团以全方位策略，透过优质临床医疗服务、医学教育和科 研，以及公众健康教育，推动公共卫生及医学发展，致力为病人提供全人关顾的优质医疗及护理 服务。 养和医院是养和医疗集团之重要成员，成立于 1922 年，为香港主要私营医院之一，以"优质服 务•卓越护理"为宗旨，致力服务大众，并积极推动医学教育和研究。 关于养和医疗集团，请浏览 www.hksh.com.

BOSTON, Sept. 19, 2023 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company focused on transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) pathway diseases, today announced that the European Medicines Agency (EMA) has issued a positive opinion on the Company’s orphan drug designation request for setmelanotide as a treatment for acquired hypothalamic obesity. “Acquired hypothalamic obesity is a serious disease with severe implications for patients and families and no effective treatment options,” said Yann Mazabraud, Executive Vice President and Head of International at Rhythm. “We are pleased with this EMA positive opinion as it underscores the significant unmet need for these patients and the potential of setmelanotide to bring a precision medicine approach that may benefit patients with this disease across Europe.” EMA orphan drug designation is granted to drugs intended for the treatment, diagnosis, or prevention of life-threatening or chronically debilitating conditions affecting no more than five in 10,000 individuals in the European Union. Rhythm is evaluating setmelanotide in a global Phase 3 clinical trial in acquired hypothalamic obesity and expects to complete patient enrollment in the fourth quarter of 2023. Acquired hypothalamic obesity is a rare form of extreme obesity that occurs following damage to the hypothalamic region of the brain, which includes the MC4R pathway and is responsible for controlling physiological functions such as hunger and weight regulation. It most frequently follows the growth or surgical removal of craniopharyngioma, astrocytoma, or other rare brain tumors. Patients experience rapid weight gain, a reduction in energy expenditure, and an increase in hunger leading to severe obesity within six to 12 months following tumor resection. Rhythm estimates there are approximately 3,500 to 10,000 patients living with acquired hypothalamic obesity in the European countries of Germany, France, Spain, Italy, The Netherlands, and the United Kingdom.1 About Rhythm Pharmaceuticals Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) diseases. Rhythm’s lead asset, IMCIVREE (setmelanotide) is approved by the U.S. Food and Drug Administration (FDA) and authorized by the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) for use in accordance with product labeling. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare MC4R pathway diseases, as well as a preclinical suite of investigational candidates for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. Setmelanotide IndicationIn the United States, setmelanotide is indicated for chronic weight management in adult andi pediatric patients 6 years of age and older with monogenic or syndromic obesity due to POMC, PCSK1 or LEPR deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1 or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS) and BBS. In the European Union, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed Bardet-Biedl syndrome (BBS) or genetically confirmed loss-of-function biallelic proopiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) deficiency in adults and children 6 years of age and above. In Canada, setmelanotide is indicated for the treatment of obesity due to Bardet-Biedl syndrome (BBS) or genetically-confirmed biallelic pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency due to variants interpreted as pathogenic, likely pathogenic, or of uncertain significance in adults and children 6 years of age and above. Limitations of Use Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benignOther types of obesity not related to POMC, PCSK1 or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity. In Europe, Setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. WARNINGS AND PRECAUTIONS Skin Monitoring: Setmelanotide may lead to generalized increased skin pigmentation and darkening of pre-existing naevi because of its pharmacologic effect. Full body skin examinations should be conducted annually to monitor pre-existing and new skin pigmentary lesions before and during treatment with setmelanotide. Heart Rate and Blood Pressure Monitoring: Heart rate and blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients treated with setmelanotide. Prolonged Penile Erection: Spontaneous penile erections have been reported in clinical trials with setmelanotide. Patients who have a penile erection lasting longer than 4 hours should be instructed to seek emergency medical attention for potential treatment of priapism. Depression: In clinical trials, depression has been reported in patients treated with setmelanotide. Patients with depression should be monitored at each medical visit during treatment with setmelanotide. Consideration should be given to discontinuing setmelanotide if patients experience suicidal thoughts or behaviors. Pediatric Population: The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated. The prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves. Excipients: This medicinal product contains 10 mg benzyl alcohol in each ml. Benzyl alcohol may cause allergic reactions. Patients who are pregnant or breastfeeding should be advised of the potential risk from the excipient benzyl alcohol, which might accumulate over time and cause metabolic acidosis. This medicinal product should be used with caution in patients with hepatic or renal impairment, because of the potential risk from the excipient benzyl alcohol which might accumulate over time and cause metabolic acidosis. Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free.” ADVERSE REACTIONS The most frequent adverse reactions are hyperpigmentation (51%), injection site reaction (39%), nausea (33%), and headache (26%). USE IN SPECIFIC POPULATIONS PregnancyThere are no data from the use of setmelanotide in pregnant women. Animal studies do not indicate direct harmful effects with respect to reproductive toxicity. However, administration of setmelanotide to pregnant rabbits resulted in decreased maternal food consumption leading to embryo-fetal effects. As a precautionary measure, setmelanotide should not be started during pregnancy or while attempting to get pregnant as weight loss during pregnancy may result in fetal harm. If a patient who is taking setmelanotide has reached a stable weight and becomes pregnant, consideration should be given to maintaining setmelanotide treatment as there was no proof of teratogenicity in the nonclinical data. If a patient who is taking setmelanotide and still losing weight gets pregnant, setmelanotide should either be discontinued, or the dose reduced while monitoring for the recommended weight gain during pregnancy. The treating physician should carefully monitor weight during pregnancy in a patient taking setmelanotide. Breast-feeding It is unknown whether setmelanotide is excreted in human milk. A nonclinical study showed that setmelanotide is excreted in the milk of nursing rats. No quantifiable setmelanotide concentrations were detected in plasma from nursing pups. A risk to the newborn/infant cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from setmelanotide therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. Fertility No human data on the effect of setmelanotide on fertility are available. Animal studies did not indicate harmful effects with respect to fertility. To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337. See Summary of Product Characteristics’ APPENDIX V for a list of European national reporting systems to communicate adverse reactions. Please see the full Prescribing Information for additional Important Safety Information. Forward-looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical progress of setmelanotide and the potential benefits and expectations of receipt of a positive opinion on the Company’s orphan drug designation request for setmelanotide as a treatment for acquired hypothalamic obesity; and expectations regarding the prevalence of patients living with acquired hypothalamic obesity. Statements using words such as “expect”, “anticipate”, “believe”, “may”, “will” and similar terms are also forward-looking statements. Such statements are subject to numerous risks and uncertainties, including, but not limited to, risks relating to our liquidity and expenses, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the ability to achieve necessary regulatory approvals, risks associated with data analysis and reporting, failure to identify and develop additional product candidates, unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, risks associated with the laws and regulations governing our international operations and the costs of any related compliance programs, our ability to obtain or maintain orphan drug designations for setmelanotide or to obtain or maintain exclusivity in any use, the impact of competition, risks relating to product liability lawsuits, inability to maintain our collaborations, or the failure of these collaborations, our reliance on third parties, risks relating to intellectual property, our ability to hire and retain necessary personnel, the impact of the COVID-19 pandemic and general economic conditions on our business and operations, including our preclinical studies, clinical trials and commercialization prospects, and the other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the three months ended June 30, 2023 and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise. Corporate Contact: David Connolly Executive Director, Investor Relations and Corporate Communications Rhythm Pharmaceuticals, Inc. 857-264-4280 dconnolly@rhythmtx.com Media Contact: Adam Daley Berry & Company Public Relations 212-253-8881 adaley@berrypr.com 1 Rhythm’s European prevalence estimate for hypothalamic obesity is limited to the EU4, UK and the Netherlands. The total 2020 population estimates for the six key countries (Germany, France, Spain, Italy, Netherlands, and UK) of 339,295,304 was used to reach a final prevalence of 0.1-0.3 in 10,000 patients.