Alstrom Syndrome

In first dedicated study of a selective IL-13 inhibitor in patients previously treated with dupilumab, the majority of patients had a history of inadequate response to dupilumab EBGLYSS also provided meaningful improvements in difficult-to-treat face and hand dermatitis The safety profile of EBGLYSS was consistent with previous Phase 3 studies and of the patients who reported eye-related events, facial dermatitis or inflammatory arthritis as the reason for prior dupilumab discontinuation, none reported similar events with EBGLYSS INDIANAPOLIS, Oct. 25, 2024 /PRNewswire/ -- New results show Eli Lilly and Company's (NYSE: LLY) EBGLYSS improved skin (including hand and face) and itch among patients with moderate-to-severe atopic dermatitis (eczema) who were previously treated with dupilumab. These results from the Phase 3b ADapt study will be presented at the Fall Clinical Dermatology (FCD) Conference from Oct. 24-27 in Las Vegas.1 EBGLYSS is an interleukin-13 (IL-13) inhibitor that selectively blocks IL-13 signaling with high binding affinity.2,3,4 The cytokine IL-13 is key in atopic dermatitis, driving the type-2 inflammatory cycle in the skin, leading to skin barrier dysfunction, itch, skin thickening and infection.5,6 "Treatment isn't one-size-fits-all, and many patients with moderate-to-severe atopic dermatitis remain in need of an effective medicine to help manage the impact of the disease, especially in difficult-to-treat areas like face and hands," said Linda Stein Gold, M.D., investigator of the ADapt study, director of dermatology research and head of the Division of Dermatology for Henry Ford Health System in Detroit, Michigan. "These data showed that EBGLYSS improved skin symptoms and reduced itch for the majority of patients who had stopped using dupilumab and complement previously presented EBGLYSS data in biologic-naive patients, further supporting that a broad range of patients could benefit from this new and effective treatment option." The ADapt study evaluated the efficacy and safety of EBGLYSS in patients with moderate-to-severe atopic dermatitis who were previously treated with dupilumab. To qualify for ADapt, patients must have discontinued dupilumab treatment due to inadequate response, intolerance or an adverse event, or other reasons (including cost or loss of access to the medicine). View an EBGLYSS patient photo from the ADapt study here.1 The primary endpoint of the study was measured by at least 75 percent improvement in the Eczema Area and Severity Index (EASI-75) score at 16 weeks, which evaluates the extent and severity of the skin disease. Secondary endpoints at 16 and 24 weeks included Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin with a reduction of at least two points from baseline and at least a four-point improvement in Pruritus NRS from baseline. Other secondary and exploratory endpoints were also included.1 The reported endpoints were as observed. With EBGLYSS, 57 percent of patients at Week 16, and 60 percent of patients at Week 24 who were previously treated with dupilumab, achieved EASI-75. These results are similar to what was observed in the Phase 3 monotherapy trials of EBGLYSS in patients without prior exposure to dupilumab (ADvocate 1 and ADvocate 2). In addition, 46 percent of patients who were inadequate responders to dupilumab achieved EASI-75 response with EBGLYSS at Week 16.1 Fifty-three percent and 62 percent of ADapt patients who discontinued dupilumab and began treatment with EBGLYSS also experienced itch relief (Pruritus NRS) with at least a four-point improvement from baseline at Week 16 and Week 24 respectively.1 Patients in this study saw improvements in difficult-to-treat areas when treated with EBGLYSS. More than half of patients (52 percent) treated with EBGLYSS saw clear or almost clear face dermatitis at Week 24 (F-IGA 0,1 with a reduction of at least two points from baseline). Among patients with moderate-to-severe hand dermatitis at baseline (defined as ≥12), patients' modified total lesion symptom score (mTLSS), which measures extent and severity of hand dermatitis, decreased by 75 percent at Week 24.1* Less than six percent of patients treated with EBGLYSS experienced an adverse event that led to treatment discontinuation.1 The safety profile of EBGLYSS in ADapt was consistent with previous EBGLYSS Phase 3 studies in patients with moderate-to-severe atopic dermatitis, and no new safety signals were observed. The majority of adverse events were mild or moderate. Reported treatment-related side effects in the study were conjunctivitis and injection site reactions. Of the 14 patients who discontinued dupilumab due to an adverse event, two patients discontinued EBGLYSS due to an adverse event. Of the 10 patients who discontinued dupilumab due to eye-related events, facial dermatitis or inflammatory arthritis, none reported similar events with EBGLYSS.1 "This trial supports the growing body of data showing that health care providers can have confidence prescribing EBGLYSS as a first-line biologic treatment for moderate-to-severe atopic dermatitis, and reinforces that EBGLYSS provided a meaningful benefit among individuals who have already tried another biologic treatment such as dupilumab and may have more difficult-to-treat disease," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. Lilly will also present additional data at the Fall Clinical Dermatology conference, including new analyses from the ADjoin long-term extension study with data up to three years. EBGLYSS was approved in the U.S. by the Food and Drug Administration (FDA) last month as a first-line biologic treatment for adults and children 12 years of age and older who weigh at least 88 pounds (40 kg) with moderate-to-severe atopic dermatitis that is not well controlled with topical prescription therapies. EBGLYSS 250 mg/2 mL injection is dosed as a single monthly maintenance injection following the initial phase of treatment. The recommended initial starting dose of EBGLYSS is 500 mg (two 250 mg injections) at Week 0 and Week 2, followed by 250 mg every two weeks until Week 16 or later when adequate clinical response is achieved; after this, maintenance dosing is a single monthly injection (250 mg every four weeks).1 EBGLYSS was also approved in the European Union in 2023, as well as in Japan in January 2024, with additional markets expected later this year. Lilly has exclusive rights for development and commercialization of EBGLYSS in the U.S. and the rest of the world outside Europe. Lilly's partner Almirall S.A. has licensed the rights to develop and commercialize EBGLYSS for the treatment of dermatology indications, including eczema, in Europe. *mTLSS is a composite measure of intensity of seven hand dermatitis signs and symptoms (erythema, edema, desquamation, fissures, hyperkeratosis/lichenification, pruritus/pain, and vesiculation, with total scores ranging from 0 to 21), used to assess improvement in hand dermatitis. About ADapt ADapt (NCT05369403), is an open-label, Phase 3b, 24-week study that evaluated the efficacy and safety of EBGLYSS in adults and adolescents (12 to less than 18 years of age and weighing ≥40 kg) with moderate-to-severe atopic dermatitis who were previously treated with dupilumab. Four or more weeks after discontinuing dupilumab, patients were treated with EBGLYSS and received a starting dosing of 500 mg (two 250 mg injections) at Week 0 and Week 2, followed by 250 mg every two weeks until Week 16. IGA 0,1 or EASI-75 responders at Week 16 received 250 mg once monthly and non-responders continued on 250 mg every two weeks until Week 24. Patients were allowed to stay on low and mid-potency topical corticosteroids.1 From baseline to Week 16, data from the ADapt study was analyzed as observed and with non-responder imputation/multiple imputation (NRI/MI). After Week 16, Q2W and Q4W data from the ADapt study were pooled and analyzed as observed and with NRI/MI.1 INDICATION AND SAFETY SUMMARY EBGLYSS™ (EHB-glihs) is an injectable medicine used to treat adults and children 12 years of age and older who weigh at least 88 pounds (40 kg) with moderate-to-severe eczema (atopic dermatitis) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. EBGLYSS can be used with or without topical corticosteroids. It is not known if EBGLYSS is safe and effective in children less than 12 years of age or in children 12 years to less than 18 years of age who weigh less than 88 pounds (40 kg). Warnings - Do not use EBGLYSS if you are allergic to lebrikizumab-lbkz or to any of the ingredients in EBGLYSS. See the Patient Information leaflet that comes with EBGLYSS for a complete list of ingredients. Before using Before using EBGLYSS, tell your healthcare provider about all your medical conditions, including if you: Have a parasitic (helminth) infection. Are scheduled to receive any vaccinations. You should not receive a "live vaccine" if you are treated with EBGLYSS. Are pregnant or plan to become pregnant. It is not known if EBGLYSS will harm your unborn baby. If you become pregnant during treatment with EBGLYSS, you or your healthcare provider can call Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) to report the pregnancy. Are breastfeeding or plan to breastfeed. It is not known if EBGLYSS passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Possible side effects EBGLYSS can cause serious side effects, including: Allergic reactions. EBGLYSS can cause allergic reactions that may sometimes be severe. Stop using EBGLYSS and tell your healthcare provider or get emergency help right away if you get any of the following signs or symptoms: breathing problems or wheezing itching swelling of the face, lips, mouth, tongue or throat fainting, dizziness, feeling lightheaded skin rash hives cramps in your stomach area (abdomen) Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, including eye pain or changes in vision, such as blurred vision. The most common side effects of EBGLYSS include: eye and eyelid inflammation, including redness, swelling, and itching injection site reactions shingles (herpes zoster) These are not all of the possible side effects of EBGLYSS. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or . How to take See the detailed "Instructions for Use" that comes with EBGLYSS for information about how to prepare and inject EBGLYSS and how to properly store and throw away (dispose of) used EBGLYSS prefilled pens and prefilled syringes. Use EBGLYSS exactly as prescribed by your healthcare provider. EBGLYSS is given as an injection under the skin (subcutaneous injection). If your healthcare provider decides that you or a caregiver can give the injections of EBGLYSS, you or a caregiver should receive training on the right way to prepare and inject EBGLYSS. Do not try to inject EBGLYSS until you have been shown the right way by your healthcare provider. In children 12 years of age and older, EBGLYSS should be given by a caregiver. If you miss a dose of EBGLYSS, inject the missed dose as soon as possible, then inject your next dose at your regular scheduled time. Learn more EBGLYSS is a prescription medicine available as a 250 mg/2 mL injection prefilled pen or prefilled syringe. For more information, call 1-800-545-5979 or go to ebglyss.lilly.com This summary provides basic information about EBGLYSS but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking to your doctor. Be sure to talk to your doctor or other healthcare provider about EBGLYSS and how to take it. Your doctor is the best person to help you decide if EBGLYSS is right for you. LK CON BS AD APP EBGLYSS™ and its delivery device base are trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. About EBGLYSS EBGLYSS is a monoclonal antibody that selectively targets and neutralizes IL-13 with high binding affinity and a slow dissociation rate.3,4,7 EBGLYSS binds to the IL-13 cytokine at an area that overlaps with the binding site of the IL-4Rα subunit of the IL-13Rα1/IL-4Rα heterodimer, preventing formation of this receptor complex and inhibiting IL-13 signaling. IL-13 is implicated as a primary cytokine tied to the pathophysiology of eczema, driving the type-2 inflammatory loop in the skin, and EBGLYSS selectively targets IL-13.7 The EBGLYSS Phase 3 program consists of five key global studies evaluating over 1,300 patients, including two monotherapy studies (ADvocate 1 and 2), a combination study with topical corticosteroids (ADhere), as well as long-term extension (ADjoin) and adolescent open label (ADore) studies. Further data results from ADjoin and ADmirable are expected to be shared in 2024 and early 2025. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about EBGLYSS (lebrikizumab-lbkz) as a treatment for patients with moderate-to severe atopic dermatitis and the timeline for future readouts, presentations, and other milestones relating to EBGLYSS and its clinical trials and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that future study results will be consistent with the results to date or that EBGLYSS will receive additional regulatory approvals, or that it will be commercially successful. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. 1 Silverberg J, et al. Lebrikizumab improves atopic dermatitis and quality of life in patients with moderate-to-severe atopic dermatitis previously treated with dupilumab: Results from the ADapt Trial. 2024 Fall Clinical Dermatology Conference. October 25, 2024. 2 Simpson EL, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018;78(5):863-871.e11. doi:10.1016/j.jaad.2018.01.017 3 Okragly A, et al. Binding, Neutralization and Internalization of the Interleukin-13 Antibody, Lebrikizumab. Dermatol Ther (Heidelb). 2023;13(7):1535-1547. doi:10.1007/s13555-023-00947-7 4 Ultsch M, et al. Structural basis of signaling blockade by anti-IL-13 antibody Lebrikizumab. J Mol Biol. 2013;425(8):1330-1339. doi:10.10116/j.jmb.2013.01.024 5 Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020;75(1):54–62. doi:10.1111/all.13954 6 Tsoi LC, et al. Atopic Dermatitis Is an IL-13-Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis. J Invest Dermatol. 2019;139(7):1480-1489. doi:10.1016/j.jid.2018.12.018 7 EBGLYSS. Prescribing Information. Lilly USA, LLC. SOURCE Eli Lilly and Company WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Rhythm will assume sponsorship of two Phase II trials investigating LG Chem’s LB54640, as part of the agreement. Image Credit: Alex Verrone / Shutterstock. Rhythm Pharmaceuticals has entered a global licensing agreement with South Korea-based LG Chem for the latter’s weight loss drug LB54640, which is currently in Phase II clinical development. Rhythm will pay $40m in cash and $20m in equity at deal closing, as per a 4 January press release. The US-based company will also pay $40m in cash 18 months after closing. LG Chem will also be entitled to receive up to $205m in milestone-based payments and royalties on sales. LB54640 is a melanocortin-4 receptor (MC4R) agonist, which simulates the MC4R pathway to reduce hunger and promote weight loss. As part of the agreement, Rhythm will assume sponsorship of two Phase II trials, SIGNAL and ROUTE, investigating LB54640. The Phase II SIGNAL trial (NCT06046443) is evaluating the drug in patients with acquired hypothalamic obesity. The placebo-controlled trial is expected to enrol approximately 28 patients. Participants will receive one of three doses of LB54640 once daily for up to 52 weeks. The primary endpoint of the study is measuring the change in body mass index (BMI) from baseline after 14 weeks of treatment. The second Phase II ROUTE trial (NCT06041841) is evaluating patients with obesity and either proopiomelanocortin (POMC) deficiency, leptin receptor (LEPR) deficiency or proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency. The open-label trial will enrol approximately five participants with either of the three genetic dispositions. The primary endpoint of the study is the change in BMI after 14 weeks of treatment compared to baseline. LB54640 demonstrated dose-dependent weight reduction in overweight adults in a Phase I trial (NCT06040372). Additionally, no changes in blood pressure or heart rate were observed. The drug received orphan drug designation from the US Food and Drug Administration (FDA) for LEPR deficiency and POMC deficiency, which are genetic disorders that cause obesity. Rhythm’s portfolio consists of another MC4R agonist Imcivree (setmelanotide). Imcivree received FDA approval for Bardet-Biedl syndrome or Alström syndrome in 2021. The weight loss management market has experienced significant growth in recent years, with Novo Nordisk being the market leader in the field. The company’s weight loss drugs Wegovy (semaglutide) and Saxenda (liraglutide) generated Dkr30.4bn ($4.36bn) in combined global sales in the first nine months of 2023, as per Novo Nordisk’s Q3 2023 financials. The overall obesity market is forecasted to grow from $6bn in 2023 to exceed $43.3bn in 2029, as per GlobalData’s market model. GlobalData is the parent company of Pharmaceutical Technology .

BOSTON, Nov. 08, 2022 (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 previously disclosed results from a Phase 3 clinical trial that evaluated IMCIVREE® (setmelanotide), an MC4R agonist, in patients with Bardet-Biedl syndrome (BBS) have been published in the peer-reviewed journal The Lancet Diabetes and Endocrinology. The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy. “Hyperphagia, which is a pathological hunger, and early-onset, severe obesity place a significant burden on both patients living with BBS and their families,” said Prof. Andrea M. Haqq, M.D., Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta. “The results from this pivotal Phase 3 clinical trial – the largest and longest interventional study ever conducted in BBS – showed patients with BBS achieved clinically significant weight loss, reductions in hunger and improvements in health-related quality of life, all of which are highly meaningful to patients with BBS and their caregivers.” Based on these pivotal Phase 3 data, IMCIVREE was approved as the first therapy for chronic weight management in adult and pediatric patients 6 years of age and older with BBS in the U.S. and European Union (EU). BBS is a rare genetic disease that affects approximately 1,500-2,500 people in the U.S. and 2,500 people in the EU and United Kingdom (UK). People living with BBS may experience insatiable hunger, also known as hyperphagia, and severe obesity beginning early in life. BBS may also be associated with cognitive impairment, polydactyly, renal dysfunction, hypogonadism and visual impairment. Rhythm’s multicenter Phase 3 trial (NCT03746522) enrolled patients ≥6 years old with obesity and BBS or Alström syndrome (N=38). Patients were randomized 1:1 to receive up to 3mg of daily subcutaneous setmelanotide or placebo in a 14-week double-blind period, followed by open-label setmelanotide for 52 weeks of treatment total. The primary endpoint was the proportion of patients ≥12 years old in the full analysis set achieving ≥10% weight reduction after 52 weeks. Hunger and safety were also assessed. As previously disclosed, treatment with setmelanotide resulted in significant weight and hunger reductions after one year of treatment among patients with BBS. The primary endpoint was achieved by 32.3% (95% confidence interval (CI), 16.7%, 51.4%; p=0.0006) of patients ≥12 years old, all of whom were patients with BBS. None of the responders were patients with Alström syndrome. Data highlights among patients with BBS (n=32) after 52 weeks of setmelanotide include: Fifteen (15) patients ≥18 years achieved a mean (SD) percent reduction in BMI of -9.1% (6.8%; 95% CI, −13.4%, −4.8%); Fourteen (14) patients <18 years achieved a mean (SD) change in BMI Z score of −0.8 (0.5; 95% CI, −1.0, −0.5), and 12 patients (85.7%) achieved ≥0.2-point reduction in BMI Z; and Fourteen (14) patients ≥12 years who reported hunger scores achieved reduction of -30.5% in maximal hunger score. The safety profile observed in this study was consistent with that observed with setmelanotide in previous clinical trials in patients with other rare MC4R pathway diseases. Skin hyperpigmentation (n=23; 60.5%) was the most common adverse event (AE). Two patients experienced serious AEs, neither of which was considered related to setmelanotide treatment. “With early, significant and sustained weight reduction demonstrated in our Phase 3 trial, we were able to secure approvals in the United States and European Union and deliver the first treatment for obesity in patients with BBS,” said David Meeker, M.D., Chair, President and Chief Executive Officer of Rhythm. “We look forward to leveraging the publication of these trial results to drive continued momentum, as we work toward our goal of bringing a new option to people who are living with this rare genetic disease around the world, while also targeting additional rare MC4R pathway diseases with our broad ongoing clinical development program.” 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) pathway diseases. Rhythm’s precision medicine, setmelanotide, 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). The European Commission (EC) has 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 UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) authorized setmelanotide for the treatment of obesity and the control of hunger associated with 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 genetic diseases of obesity and is leveraging the Rhythm Engine and the largest known obesity DNA database -- now with approximately 45,000 sequencing samples -- to improve the understanding, diagnosis and care of people living with severe obesity due to certain genetic deficiencies. 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 Bardet-Biedl syndrome (BBS) or genetically confirmed loss-of-function biallelic pro-opiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) deficiency in adults and children 6 years of age and above. Limitations of Use In the United States and Europe, Setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. 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. 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 Pregnancy There 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-foetal 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.