Rhythm Pharmaceuticals Announces FDA Approval of IMCIVREE® (setmelanotide) for Use in Patients with Bardet-Biedl Syndrome
-- IMCIVREE now available for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to Bardet-Biedl syndrome --
-- First and only FDA-approved therapy that targets impairment in the MC4R pathway - a root cause of early-onset, severe obesity and hyperphagia associated with Bardet-Biedl syndrome --
-- Approval based on Phase 3 trial results that demonstrated statistically significant reductions in weight and hunger in patients with Bardet-Biedl syndrome --
-- Management to host conference call today at 5:00 p.m. ET --
BOSTON, June 16, 2022 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company committed to transforming the care of people living with rare genetic diseases of obesity, today announced that the U.S. Food and Drug Administration (FDA) has approved the Company’s supplemental New Drug Application (sNDA) for IMCIVREE® (setmelanotide), a melanocortin-4 receptor (MC4R) agonist, for patients with Bardet-Biedl syndrome (BBS).
With today’s approval, IMCIVREE is indicated for chronic weight management in adult and pediatric patients 6 years old and older with monogenic or syndromic obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency, or BBS.
“This FDA approval represents a significant milestone for Rhythm, validating our strategy of developing IMCIVREE for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, M.D., Chair, President and Chief Executive Officer of Rhythm. “Leveraging the robust infrastructure we put in place following the initial approval of IMCIVREE for obesity due to biallelic POMC, PCSK1 or LEPR deficiency and our new high-touch patient support services to assist patients throughout the journey from diagnosis to ongoing treatment, we are able to make IMCIVREE available for BBS immediately. We look forward to delivering this important medicine to the growing community of patients and families in need of options that can effectively address the obesity and hyperphagia that affect many people living with BBS.”
IMCIVREE was initially approved by the FDA in November 2020 for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to POMC, PCSK1 or LEPR deficiency. IMCIVREE’s label was updated today to include an FDA-approved test developed under a post-marketing commitment to confirm variants in POMC, PCSK1 or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).
IMCIVREE is not indicated for the treatment of patients with obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benign, or 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.
In clinical trials, IMCIVREE was generally well-tolerated. Disturbance in sexual arousal, depression and suicidal ideation, increased skin pigmentation and darkening of pre-existing nevi, and benzyl alcohol toxicity in neonates and low birth-weight infants may occur. The most common adverse reactions were skin hyperpigmentation, injection site reactions and nausea.
BBS is a rare genetic disease that affects approximately 1,500-2,500 people in the U.S. 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.
Robert Haws, M.D., a BBS expert who recently retired from his role as Director of the Center of Excellence for Bardet-Biedl Syndrome at the Marshfield Clinic Research Institute in Wisconsin, said, “This approval marks an important achievement for the entire BBS community including patients and their families, clinicians and researchers, as we all have been looking forward to a therapy that addresses the burdens of hyperphagia and severe obesity that significantly affect daily lives of patients and caregivers living with BBS. IMCIVREE achieved significant reductions in weight and hunger in patients with BBS, providing this community a much needed and first-ever therapeutic option.”
“It is important to understand that the early-onset, severe obesity and pathologic hunger experienced by many people living with BBS can be debilitating, especially when you consider the impact of food-seeking behavior on families,” said Timothy Ogden, President, BBS Foundation and Family Association. “Challenges in managing weight and hunger have dramatically negative effects on health, well-being, and quality of life for those living with BBS, and we are thrilled finally to have a new treatment option to address this significant unmet need.”
Data from Phase 3 trial evaluating IMCIVREE in BBS
As presented in the label, in patients aged =6 years with obesity due to BBS (N=31):
Rhythm also announced that the FDA issued a complete response letter for the sNDA for setmelanotide in Alström syndrome. Rhythm plans to reevaluate potential paths forward in Alström syndrome in the U.S.
“We appreciate the FDA’s careful review of our sNDA for IMCIVREE for the treatment of Alström syndrome, but are disappointed in this outcome,” added Dr. Meeker. “We are tremendously grateful to the Alström syndrome patients, caregivers and physicians wh participated in our clinical development efforts and look forward to providing an update regarding our path forward.”
Rhythm InTune offers personalized support to patients, caregivers and physicians
Conference call information
In the EU and Great Britain, IMCIVREE is indicated 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. IMCIVREE should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology.
Rhythm’s Type II variation application to the European Medicines Agency (EMA) for the treatment of obesity and control of hyperphagia in adult and pediatric patients 6 years of age and older with BBS is under review. The Company is also continuing to advance the most comprehensive clinical research program ever initiated in MC4R pathway diseases, including the pivotal Phase 3 EMANATE clinical trial evaluating setmelanotide in four independent sub-studies in patients with obesity due to POMC insufficiency caused by heterozygous variants in the POMC or PCSK1 genes, LEPR insufficiency caused by heterozygous variants in the LEPR gene, SRC1 deficiency caused by a variant in the NCOA1 gene, and SH2B1 deficiency caused by a variant in the SH2B1 gene or 16p11.2 deletion encompassing the SH2B1 gene. The Phase 2 DAYBREAK trial is evaluating setmelanotide in patients with severe obesity and hyperphagia caused by rare variants associated with 10 prioritized MC4R-relevant genes. Rhythm has also initiated a Phase 3 pediatric trial and a Phase 3 trial evaluating a weekly formulation of setmelanotide.
IMCIVREE® (setmelanotide) Indication
Limitations of Use
WARNINGS AND PRECAUTIONS
Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.
Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur.
Skin Pigmentation and Darkening of Pre-existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmentary lesions.
Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: IMCIVREE 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.
USE IN SPECIFIC POPULATIONS
To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at 833-789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see the full Prescribing Information for additional Important Safety Information.
About Rhythm Pharmaceuticals
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