Congenital Hyperinsulinism

BOSTON and LONDON, Oct. 24, 2024 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM) and Axovia Therapeutics Ltd. today announced a joint research collaboration designed to advance the understanding of Bardet-Biedl syndrome (BBS). “We believe there is a significant need and opportunity with the growing awareness of BBS to better understand the disease and its epidemiology,” said Prof. Phil Beales, Axovia Therapeutics’ Chief Executive Officer and Co-Founder. “At Axovia, we are utilizing gene therapy to address the loss of sight and obesity experienced by patients with BBS, and we are pleased to be collaborating with Rhythm, a global company that has pioneered research in the melanocortin-4 receptor pathway and developed the first and only commercially available drug to help treat hyperphagia and severe obesity in patients living with BBS. Rhythm and Axovia Therapeutics are natural collaborators in such an effort.” “Prof. Beales is a leading expert on BBS and was involved in creating the original diagnostic criteria for patients living with this disease,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “We are excited to work together with Axovia Therapeutics to advance our shared understanding of the disease and pool the knowledge we have gained from our respective screening efforts with the goal of further improving the lives of patients and their families living with BBS.” About Bardet-Biedl syndrome (BBS)BBS is a rare autosomal recessive ciliopathy that presents with a variety of signs and symptoms that evolve over time including visual impairment, renal disease, polydactyly, genital abnormalities, cognitive impairment, hyperphagia and early-onset, severe obesity arising from impairment of the hypothalamic MC4R pathway. In the United States, BBS affects approximately 4,000 to 5,000 individuals with similar prevalence in Europe. About Axovia TherapeuticsAxovia Therapeutics is leading the development of therapies that address the genetic causes of blindness and obesity which are driven by ciliopathies. Ciliopathies are a group of more than 50 inherited genetic diseases linked to more than 950 genes that impact the function of cilia which are critical for protein transport and cellular signaling. The company is positioned to initiate clinical studies for its lead program for Bardet-Biedl Syndrome (BBS), AXV-101, in mid-2025 based on robust preclinical data, scaled manufacturing and established patient registries. The initial subretinal study is designed to halt photoreceptor cell death and retinal degeneration and the CNS delivery program, which will begin in 2026, will seek to address hyperphagia and obesity. AXV-101 has achieved U.S. Food and Drug Administration Orphan Drug Designation and Rare Pediatric Disease Designation. Axovia was formed following decades of work on ciliopathies at University College London by co-founders Professor Phil Beales and Dr. Victor Hernandez. About Rhythm PharmaceuticalsRhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients 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. The EC has also authorized setmelanotide for control of hunger and treatment of obesity in children as young as 2 years old, living with BBS or POMC, PCSK1, or LEPR deficiency. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists LB54640 and RM-718, and a preclinical suite of small molecules 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 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 benign.Other 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 U.S. Prescribing Information and EU Summary of Product Characteristics 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 progress, potential regulatory submissions, approvals and timing thereof of setmelanotide and our other product candidates, and our business strategy and plans, the potential benefits of a joint research collaboration between Rhythm and Axovia Therapeutics, and the potential of Rhythm’s and Axovia Therapeutics’ drug candidates to provide treatment options for patients with BBS. 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, 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 June 30, 2024 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. Rhythm Contacts: Corporate:David ConnollyHead of Investor Relations and Corporate CommunicationsRhythm Pharmaceuticals, Inc.857-264-4280dconnolly@rhythmtx.com Media:Sheryl SeapyReal Chemistry(949) 903-4750sseapy@realchemistry.com Axovia Contact:Professor Phil BealesChief Executive Officerinvestors@axovia.com

减肥药概念股Zealand公司再次受挫，推出的用以治疗儿童先天性高胰岛素血症(CHI)的上市申请的新药Dasiglucagon再次遭到了FDA拒绝。 去年12月，因为发现第三方合同制造工厂缺陷，Dasiglucagon首次被FDA拒之门外。 Zealand指出，Dasiglucagon二次被拒主要原因在于，FDA对第三方生产工厂的复检没能完成，导致审批进程搁置，FDA并没有提出对dasiglucagon有效性或安全性的担忧。 Dasiglucagon是一种胰高血糖素受体（GCGR）激动剂，其作用是使肝脏将储存的糖原释放到血液中。 低血糖是糖尿病最常见的急性并发症之一，患者在有能力持续监测血糖的情况下也并不能完全预防严重低血糖事件。 与未发生严重低血糖的患者相比，发生严重低血糖的2型糖尿病患者心力衰竭以及动脉粥样硬化性心血管疾病的风险增加，全因死亡率和短暂性脑缺血发作风险均增加。此外，反复发作的低血糖可能加剧患者的脑缺血性损伤，影响患者免疫反应等。 2021年，Dasiglucagon获得FDA批准上市，用于治疗6岁及以上糖尿病患者的严重低血糖。2022年6月，Zealand与诺和诺德就Dasiglucagon全球许可和开发协议，总交易额为4575万美元，Dasiglucagon将该药的全球商业化交给了后者负责。 Zealand成立于1998年，公司与另一家诺和诺德在地理位置上只隔几英里，Zealand的 CEO在内的多位管理层也曾有在诺和诺德工作的经历。 2010年和2017年，Zealand分别在在丹麦哥本哈根交易所上市以及美国纳斯达克交易所和上市。 Zealand最初也是做降糖，Zealand推出的首个上市产品——利西拉来就是一款GLP-1受体激动剂，不过在2003年便授权给了赛诺菲。 近年来因为减肥药的大火，加上之后推出的Dasiglucagon销售业绩表现不佳，Zealand也转变了研发方向，专注于减重药的开发。 可以说，这个战略转变对于Zealand的起死回生十分关键，受到减重药利好临床数据的拉动，公司近一年股价上涨了158%。 Zealand围绕减重布局了多款管线，其中最快的Survodutide已经推进到Ⅲ期临床阶段，Survodutide是一种GCGR/GLP-1R双靶点激动剂，与勃林格殷格合作开发，适应症包括减重和MASH。 Zealand还开发了全球首款GLP-1/GLP-2双重激动剂Dapiglutide，目前已经推进到临床Ⅱ期阶段。 上个月，Zealand公布了dapiglutide用于减重的II期临床数据，13周时，Dapiglutide组最高减重6.2%，而安慰剂组体重增加了2.1%。 还有两款减重管线——一种胰淀素类似物Petrelintide、以及一款GIP受体激动剂ZP6590。 因为Dasiglucagon卖的不行，本来Zealand也是缺钱的，去年公司还与一家欧洲投资银行签署了一项9000万欧元的贷款融资协议。 今年公司财务状况明显好转，在股票市场的正向表现令公司今年6月通过增发募资了70亿丹麦克朗（约合10亿美元），解下了资金燃眉之急。 去年底，Zealand还向FDA递交另外一款新药的上市申请——glepaglutide，一种长效胰高血糖素样肽-2（GLP-2）类似物，用于治疗依赖肠外营养支持的成人短肠综合征患者。 参考出处： Zealand's hypoglycemia drug suffers another FDA rejection tied to CDMO inspection | Fierce Pharma FDA knocks back Zealand's dasiglucagon once again | pharmaphorum

Zealand Pharma provides U.S. regulatory update on dasiglucagon in congenital hyperinsulinism U.S. Food and Drug Administration (FDA) issues Complete Response Letter (CRL) for dasiglucagon in CHI for up to three weeks of dosing due to the timing of a third-party manufacturing facility reinspection The reinspection of the facility was completed in August/September 2024 for which a new inspection classification is pending Zealand remains committed to working with the FDA and the third-party manufacturer to bring dasiglucagon to patients in the U.S. as soon as possible October 9, 2024 – Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for Part 1 of the New Drug Application (NDA) for dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with congenital hyperinsulinism (CHI) for up to 3 weeks of dosing. The CRL is related to the timing of a reinspection at a third-party contract manufacturing facility that was completed in August/September 2024. The third-party manufacturer has not yet received its inspection classification following the reinspection. A prior inspection of the facility had identified deficiencies that did not involve dasiglucagon. These prior deficiencies had been resolved as of this reinspection. The CRL did not state any concerns about the clinical data package or safety of dasiglucagon. “We at Zealand Pharma are acutely aware of the significant unmet medical need for newborns and children with congenital hyperinsulinism who have either no or very limited treatment options today,” said David Kendall, M.D., Chief Medical Officer of Zealand Pharma. “We are committed to working with the FDA and our third-party manufacturing partner to bring dasiglucagon to patients living with this devastating disease in the months ahead.” The regulatory review of dasiglucagon is being conducted in two parts under the same NDA. Part 1 relates to dosing of up to 3 weeks and Part 2 relates to the use beyond 3 weeks. Supporting the use of dasiglucagon in CHI beyond 3 weeks, the FDA requested additional analyses from existing continuous glucose monitoring (CGM) datasets from the Phase 3 clinical program. Zealand expects to submit these data by the end of 2024. Congenital hyperinsulinism (CHI) is a severe, ultra-rare genetic disease, primarily affecting infants and children, in which the pancreatic beta cells dysfunction and secrete too much insulin, leading to frequent, recurrent, and often severe episodes of hypoglycemia. Persistent episodes of hypoglycemia can result in seizure, brain damage and death.1,2 It is estimated that CHI develops in one out of 50,000 (or more) children, corresponding to 180-300 newborns being diagnosed with the disease in the US and Europe every year.3,4 CHI has a significant impact on patient quality of life. Complex care requirements, including continuous intravenous infusion of glucose, can result in lengthy and frequent hospitalizations and make daily social activities difficult for both patients and their families. The only currently approved medical treatment for hyperinsulinism is diazoxide, which can be associated with increased risk of fluid retention, pulmonary hypertension, and congestive heart failure.5 Glucagon and the somatostatin analog octreotide may be used but are not approved therapies. It is estimated that more than 50% of CHI patients do not respond adequately to the medical treatment options currently available, so there remains a significant unmet medical need for more and better treatment options.6 Dasiglucagon is a glucagon receptor agonist that works by causing the liver to release stored sugar to the blood and is being evaluated for the prevention and treatment of hypoglycemia in infants and children with congenital hyperinsulinism. Dasiglucagon is designed to be administered by continuous subcutaneous infusion using a wearable pump system. Zealand Pharma has a collaborative development and supply agreement with DEKA Research & Development Corporation and affiliates for the wearable subcutaneous infusion pump system. Zealand Pharma A/S (Nasdaq: ZEAL) ("Zealand") is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development. The company has development partnerships with a number of pharma companies as well as commercial partnerships for its marketed products. Zealand was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the U.S. For more information about Zealand’s business and activities, please visit www.zealandpharma.com. References 1) Thornton PS et al. (2015) Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children, J Pediatr. 2015;167(2):238-45. 2) Banerjee I et al. (2022) Correction to: Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families, Orphanet J Rare Dis. 2022;17:61. 3) Arnoux JB et al. (2011) Congenital hyperinsulinism: current trends in diagnosis and therapy, Orphanet J Rare Dis. 2011; 6:63. 4) Yau et al. (2020) Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389, Plos One. 2020;15(2). 5) PROGLYCEM® (diazoxide) oral suspension package insert (07/18/2024) https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/017453s024lbl.pdf (accessed October 7, 2024) 6) Yorifuji et al. (2017) Clinical practice guidelines for congenital hyperinsulinism, Clin Pediatr Endocrinol. 2017;26(3):127-152. The content above comes from the network. if any infringement, please contact us to modify.