Overview

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 diseases of obesity.”

–David Meeker, M.D., CEO

Rhythm’s Pipeline

Setmelanotide is a melanocortin-4 receptor (MC4R) agonist designed to address the underlying cause of obesities driven by genetic variants that impair 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 2021, it was authorised by the European Commission and Great Britain’s MHRA 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 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:

Complete
Denotes study underway
Denotes planned study

STUDY

PHASE

Setmelanotide (daily)

Bardet-Biedl and Alström syndromes

FDA Prescription Drug User Fee Act target date of June 16, 2022

PHASE 3

EMANATE

Heterozygous POMC/PCSK1 deficiency
Heterozygous LEPR deficiency
SRC1 deficiency SH2B1 deficiency

PHASE 3

Pediatrics Trial

Patients (ages 2 to younger than 6) with obesity due to biallelic POMC, PCSK1 or LEPR deficiency or BBS

PHASE 3

DAYBREAK

Additional 10 genes with strong or very strong relevance to MC4R

PHASE 2

Exploratory Basket Study

Several cohorts ongoing

PHASE 2

Hypothalamic Obesity

Open-label

PHASE 2

Setmelanotide (weekly)

Switch Trial

Patients previously in open-label extension study of daily setmelanotide*, ,

PHASE 3

De Novo Trial

Patients with BBS naive to setmelanotide therapy

PHASE 3

* Patients with obesity due to biallelic or heterozygous POMC, PCSK1 or LEPR deficiency or a clinical diagnosis of BBS with genetic confirmation.

Complete

Denotes study underway

Denotes planned study

PHASE 2

PHASE 3

Setmelanotide (daily)

EMANATE

POMC insufficiency obesity
LEPR insufficiency obesity
SRC1 deficiency obesity
SH2B1 deficiency obesity

Pediatrics Trial

Pediatrics (age 2 to <6 years); POMC or LEPR deficiency obesity or BBS

DAYBREAK

Additional 10 genes with strong or very strong relevance to the MC4R pathway

Exploratory Basket Trial

Several cohorts

Hypothalamic Obesity

Open-label

Setmelanotide (weekly)

Switch 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.

Genetic diseases that present with severe obesity early in life

The severe obesity and hyperphagia that characterize rare genetic diseases of obesity 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