A comprehensive clinical development program
“Through multiple clinical trials, we are exploring opportunities to extend the reach of our precision medicine to address the needs of many more patients with early-onset, severe obesity and hyperphagia. Our goal is to deliver new options to these patients who otherwise have no approved therapies that specifically address the underlying cause of their rare MC4R pathway diseases.”
–David Meeker, M.D., CEO
Setmelanotide is a melanocortin-4 receptor (MC4R) agonist designed to address the underlying cause of obesities driven by impaired function of the MC4R pathway.
IMCIVREE (setmelanotide) has been approved by the U.S. Food and Drug Administration for chronic weight management in adult and pediatric patients 6 years old and older with monogenic or syndromic obesity due to POMC, PCSK1 or LEPR deficiency or Bardet-Biedl syndrome (BBS). In Europe, IMCIVREE has been authorized by the European Commission and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) 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. IMCIVREE has been generally well-tolerated. Disturbance in sexual arousal, depression and suicidal ideation, and skin pigmentation and darkening of pre-existing nevi may occur. The most common adverse reactions were skin hyperpigmentation, injection site reactions and nausea. For more information, including important safety information, visit IMCIVREE.com.
We are advancing setmelanotide in several additional trials. Here is our investigational pipeline:
We are advancing setmelanotide in several addition trials. Here is our investigational pipeline:
Heterozygous POMC/PCSK1 deficiency
Heterozygous LEPR deficiency
SRC1 deficiency SH2B1 deficiency
Patients (ages 2 to younger than 6) with obesity due to biallelic POMC, PCSK1 or LEPR deficiency or BBS
Additional genes with strong or very strong relevance to MC4R
Exploratory Basket Study
Patients with BBS naive to setmelanotide therapy
* Patients with obesity due to biallelic or heterozygous POMC, PCSK1 or LEPR deficiency or a clinical diagnosis of BBS with genetic confirmation.
Denotes study underway
Denotes planned study
POMC insufficiency obesity
LEPR insufficiency obesity
SRC1 deficiency obesity
SH2B1 deficiency obesity
Additional genes with strong or very strong relevance to the MC4R pathway
Exploratory Basket Trial
Patients previously in open-label extension study of daily setmelanotide*
De Novo Trial
Patients with BBS naive to setmelanotide therapy
* Patients with obesity due to biallelic or heterozygous POMC, PCSK1 or LEPR deficiency or a clinical diagnosis of BBS.
Opportunity to extend the reach of our precision medicine
The Phase 3 EMANATE trial and the Phase 2 DAYBREAK trial are evaluating setmelanotide in people with obesity and a variant in certain genes with strong or very strong relevance to the MC4R pathway.
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Rare MC4R pathway diseases that present with severe obesity early in life
The severe obesity and hyperphagia that characterize rare MC4R pathway diseases often present early in life. That is why Rhythm initiated a Phase 3 trial in pediatric patients.
The trial includes patients ages 2 to younger than 6 years old who have obesity due to biallelic proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency or a clinical diagnosis of Bardet-Biedl syndrome (BBS).
For more information, visit ClinicalTrials.gov
Potential to improve convenience for patients and caregivers
Rhythm is evaluating a once-weekly formulation of setmelanotide designed to provide similar efficacy and to improve compliance and adherence.
In a completed trial in healthy volunteers living with obesity, data showed that a once-weekly formulation of setmelanotide achieved safety and efficacy results comparable to the daily-dosing formulation.
Rhythm is advancing two Phase 3 trials evaluating a once-weekly formulation of setmelanotide:
- Phase 3 switch trial evaluating a weekly formulation of setmelanotide in patients 6 years of age and older with a rare genetic disease of obesity who are currently taking the daily formulation of setmelanotide.
- Phase 3 de novo trial to evaluating the weekly formulation of setmelanotide in patients with BBS who have not previously taken setmelanotide. This trial is being conducted in Europe and the Middle East.
Learn more about Rhythm’s clinical trials process
Rhythm’s areas of interest for investigator-initiated studies are focused on MC4R pathway related diseases, including but not limited to natural history, genotype-phenotype correlations, energy expenditure, hyperphagia and real-world experience with setmelanotide. Studies designed for general obesity or non-rare diseases are not within our scope. For more information, please email [email protected].