Setmelanotide as a Protein replacement agent: USP Medicare Modeling Guidelines – 10/5/23

On September 29th, The United States Pharmacopeia (USP) issued the Medicare Modeling Guidelines (MMG) version 9.0 including setmelanotide as a Protein replacement agent

Updates to USP Medicare Modelling Guidelines include changes in therapeutic uses of covered Part D drugs and the additions of new covered Part D drugs. Anti-obesity agents are not included in the USP-MMG guidelines.

• The USP Medicare Model Guidelines (MMG) is an independent drug classification system designed for Centers for Medicare & Medicaid Services (CMS) Part D formulary submissions

• Being recognized as a “Genetic or Enzyme or Protein Disorder: Replacement, Modifiers, Treatment” means that setmelanotide is not categorized as an anti-obesity agent by USP

• The members of the USP Council of Experts, the Healthcare Safety and Quality Expert Committee (HSQ EC) comprised of independent pharmacologists, clinical pharmacists, academicians, formulary specialists, providers, beneficiaries, drug information experts and healthcare policy experts, are responsible for developing these guidelines

• Historically, every three years, USP publishes an updated version of MMG, which includes a list of categories and classes that may be used by Part D prescription drug plans

With this recent update by USP-MMG, IMCIVREE is now classified as a protein replacement agent

Across four major clinical compendia including:

- USP Drug Classification (DC) 2023

- USP MMG v9.0

- AHFS Clinical Drug Information

- MicroMedex by Merative

Indication and Important Safety Information

Indication

IMCIVREE is indicated 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 (BBS).

Limitations of Use

IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective:

• Other types of obesity not related to BBS or other FDA-approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity

Important Safety Information

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.

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

Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

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.

© 2023, Rhythm Pharmaceuticals, Inc. All rights reserved.

Rhythm, IMCIVREE, and their logos are trademarks of Rhythm Pharmaceuticals, Inc. US-SET-2200172 08/2022