IMCIVREE FAQ

Acquired HO is caused by impairment of the MC4R pathway, a key hormonal pathway that regulates energy balance.¹

Injury to the hypothalamic-pituitary region commonly results in hypothalamic dysfunction, which may result in acquired HO. Causes of injury may include, but are not limited to^2,3:

• Hypothalamic-pituitary tumors, including craniopharyngioma, astrocytoma, and pituitary adenomas
• Tumor treatment
• Traumatic brain injury
• Hypothalamic inflammation
• Stroke

A clinical diagnosis of acquired HO is defined by weight gain due to hypothalamic injury. Diagnosis of acquired HO should be considered in patients with^2-5:

• A history of hypothalamic injury resulting from hypothalamic-pituitary tumors and/or their treatment, traumatic brain injury, hypothalamic inflammation, or stroke
• Evidence of hypothalamic dysfunction, including hypopituitarism and especially accompanied by increased hunger or hyperphagia
• Weight gain, which may be accelerated and sustained and can occur despite caloric restriction and/or increased physical activity

The MC4R pathway plays a fundamental role in regulating energy intake and expenditure to maintain energy balance, and in turn, regulate weight. α-Melanocyte stimulating hormone (α-MSH) is the endogenous MC4 receptor ligand.¹

Injury to the hypothalamic-pituitary region can impair production of various hormones, including α-MSH. Deficient production of α-MSH leads to decreased MC4 receptor activation and impaired MC4R pathway function, which can lead to acquired hypothalamic obesity (HO).^1,6

IMCIVREE is the first and only treatment that targets impairment of the hypothalamic MC4R pathway, the root cause of acquired HO. Impaired MC4R pathway function can dysregulate energy balance and satiety, which may lead to increased hunger, food intake, and weight gain^1,6

IMCIVREE is an MC4 receptor agonist that bypasses deficient α-melanocyte stimulating hormone (α-MSH) production to help activate the MC4R pathway. MC4R pathway activation helps increase energy expenditure and satiety, reducing hunger, food intake, and weight.⁶

In a randomized, double-blind, placebo-controlled Phase 3 trial of 142 patients (IMCIVREE, n=94; placebo, n=48) with acquired HO, IMCIVREE delivered significant improvements in weight and hunger⁶:

• IMCIVREE delivered a significant 18.4% placebo-adjusted reduction in BMI at 52 weeks (15.8% mean reduction for IMCIVREE vs 2.6% mean increase for placebo; p<0.0001)
• IMCIVREE delivered significant hunger reduction in patients 12 years and older

Other secondary endpoints evaluated included Impact of Weight on Quality of Life score, waist circumference, and cardiometabolic parameters. These endpoints were not included in the statistical testing hierarchy and were not controlled for multiplicity.^6,7

For patients 4 years and older (N=142; IMCIVREE, n=94; placebo, n=48):

• 18.4% placebo-adjusted reduction in BMI at 52 weeks (15.8% mean reduction for IMCIVREE vs 2.6% mean increase for placebo; p<0.0001)⁶

For patients 4 to <18 years old (n=76; IMCIVREE, n=49; placebo, n=27):

• 18.2% placebo-adjusted reduction in BMI for patients 4 to <18 years old at 52 weeks on a therapeutic dose (n=76)⁷
  • 15.3% mean reduction for IMCIVREE vs 3.0% mean increase for placebo⁷
• 26-point mean reduction in the BMI percent of the 95th percentile for IMCIVREE vs 0.6-point mean reduction for placebo⁷

For patients 4 years and older (N=142; IMCIVREE, n=94; placebo, n=48):

• 18.4% placebo-adjusted reduction in BMI at 52 weeks (15.8% mean reduction for IMCIVREE vs 2.6% mean increase for placebo; p<0.0001)⁶

For patients 18 and older (n=66; IMCIVREE, n=45; placebo, n=21):

• 18.8% placebo-adjusted reduction in BMI for patients 18 and older at 52 weeks on a therapeutic dose (n=66)⁷
  • 16.6% mean reduction for IMCIVREE vs 2.2% mean increase for placebo⁷
• 45% of patients achieved a BMI <30 at 52 weeks, below the threshold for obesity⁷

IMCIVREE has a well-established safety and tolerability profile. The most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, nausea, vomiting, and headache. Nausea and vomiting occurred most frequently within the first month of treatment, then declined.^6,7

Please follow the link below and review the full Prescribing Information for additional Important Safety Information.

In patients with secondary adrenal insufficiency: monitor for clinical signs of acute adrenal insufficiency.⁶

In patients with concurrent diabetes insipidus (DI)/arginine vasopressin (AVP) deficiency: monitor serum sodium levels with changes in fluid intake and hydration status. Adjust the doses of concomitant therapies as needed.⁶

Please follow the link below and review the full Prescribing Information for additional Important Safety Information.

Hyperpigmentation with IMCIVREE is common and variable. IMCIVREE is an MC4 receptor agonist that has some residual activity at the MC1 receptor. Activation of the MC1 receptor can lead to the accumulation of melanin, resulting in hyperpigmentation. In clinical trials, measures of hyperpigmentation increased throughout the dose escalation period and generally plateaued in the initial months of treatment.^6,8

If hyperpigmentation is a concern, assess patient response to treatment to optimize tolerability and efficacy as you would with other adverse events. It is important to remember that continued treatment with IMCIVREE is necessary to sustain clinical benefits, including reduced weight and hunger.

IMCIVREE is a once-daily subcutaneous injection, administered⁶:

• At the beginning of the day
• With or without food
• In the abdomen, thigh, or arm, rotating injection sites daily

IMCIVREE can be self-administered or given by a caregiver. Refrigerated storage is recommended, with room temperature storage permitted for up to 30 days.⁶

IMCIVREE is dosed by age and, for patients 4 to <6 years of age, by weight. Follow the titration schedule to reach a maintenance dose to optimize efficacy and tolerability.⁶

Please follow the link below to find your patient’s titration schedule.

To prescribe IMCIVREE, download the IMCIVREE Prescription Start Form. Complete all fields in the Start Form, making sure to select the appropriate indication and dosage, and fax the completed Start Form to 1-877-805-0130 or email patientsupport@rhythmtx.com.

Patients can enroll in Rhythm InTune by completing the consent section of the IMCIVREE Prescription Start Form.

To help avoid unnecessary delays during the insurance approval process:

• Use the IMCIVREE Prescription Start Form
• Complete all fields in the form
• Ensure the appropriate indication and dosage are selected

If e-prescribing, please be sure to:

• Select PANTHERx Rare Pharmacy in the US, or Special Care Pharmacy Services in Puerto Rico
• Consider also submitting the Prescription Start Form, which includes the Rhythm InTune patient consent form and additional information fields often required for insurance approval, as these are not typically included when e-prescribing

Rhythm InTune is a patient support program that helps patients stay on track along their IMCIVREE journey:

1. Patient Access: The majority of patients, regardless of coverage type, have obtained approval for IMCIVREE. Financial assistance programs are available for eligible patients.
2. Starting Treatment: Patients and caregivers may choose to receive personalized injection training, as well as education on what to expect in the first 90 days.
3. Ongoing Treatment: Patients and caregivers may receive ongoing wellness tips, disease education, and help connecting with others living with acquired HO.

Patients can enroll in Rhythm InTune by completing the consent section of the IMCIVREE Prescription Start Form or can learn more by visiting RhythmInTune.com.