ph-91109
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Imcivree Prior Authorization with Quantity Limit

Policy Number: PH-91109

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

Imcivree Prior Authorization with Quantity Limit

TARGET AGENT(S)

Imcivree (setmelanotide)

Brand (generic)

GPI

Multisource Code

Quantity Limit

(per day or as listed)

Imcivree (setmelanotide)

10 mg/mL multiple-dose vial (1 mL)

61253860102020

M, N, O, or Y

10 vials / 30 days

PRIOR AUTHORIZATION CRITERIA FOR APPROVAL

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. The patient’s benefit plan covers the requested agent

AND

  1. ONE of the following:
    1. The patient’s age is within FDA labeling for the requested indication for the requested agent

OR

    1. The prescriber has provided information in support of using the requested agent for the patient’s age

AND

  1. The patient has a diagnosis of obesity and ONE of the following:
    1. BOTH of the following:
      1. The patient has proopiomelanocortin (POMC) deficiency

AND

      1. Genetic testing has confirmed a mutation in the POMC gene (medical records required)

OR

    1. BOTH of the following:
      1. The patient has proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency

AND

      1. Genetic testing has confirmed a mutation in the PCSK1 gene (medical records required)

OR

    1. BOTH of the following:
      1. The patient has leptin receptor (LEPR) deficiency

AND

      1. Genetic testing has confirmed a mutation in the LEPR gene (medical records required)

AND

  1. ALL of the following:
    1. The patient’s genetic status is bi-allelic, homozygous, or compound heterozygous (NOT double heterozygous)

AND

    1. The patient’s genetic variant is interpreted as pathogenic, likely pathogenic, OR of uncertain significance (VUS)

AND

    1. The patient’s genetic variant is NOT classified as benign or likely benign

AND

  1. ONE of the following:
    1. For adult patients, the body mass index (BMI) is ≥30 kg/m2

OR

    1. For pediatric patients, weight is ≥95th percentile using growth chart assessments

AND

  1. ONE of the following:
    1. The patient is newly starting therapy

OR

    1. The patient is currently being treated and has received less than 16 weeks (4 months) of therapy

OR

    1. The patient has received at least 16 weeks of therapy, and has achieved and maintained a weight loss of ONE of the following:
      1. Weight loss of ≥5% of baseline body weight (prior to the initiation of the requested agent)

OR

      1. For patients with continued growth potential, weight loss of ≥5% of baseline BMI (prior to the initiation of the requested agent)

AND

  1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., geneticist, metabolic disorders) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis

AND

  1. The patient does NOT have any FDA labeled contraindications to the requested agent

AND

  1. ONE of the following:
    1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

AND

      1. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

Length of Approval:  4 months

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process

AND

  1. The patient’s benefit plan covers the requested agent

AND

  1. ONE of the following:
    1. For adult patients, the patient has achieved and maintained weight loss of ≥5% of baseline body weight (prior to the initiation of the requested agent)

OR

    1. For patients with continued growth potential, weight loss of ≥5% of baseline BMI (prior to the initiation of the requested agent)

AND

  1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., geneticist, metabolic disorders) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis

AND

  1. ONE of the following:
    1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

AND

      1. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

Length of Approval:  12 months

 

FDA APPROVED INDICATIONS AND DOSAGE1

Agent(s)

Indication(s)

Dosage

Imcivree

(setmelanotide)

SC injection

Chronic weight management in adult and pediatric patients 6 years of age or older with obesity due to proopiomelanocortin (POMC), proprotein convertase

subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic

testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as

pathogenic, likely pathogenic, or of uncertain significance (VUS)

Limitations of Use:

  • Not indicated for the treatment of obesity due to POMC, PCSK1, or LEPR variants classified as benign or likely benign
  • Not indicated for the treatment of other types of obesity not related to POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general obesity

Patients ≥12 years of age:

Starting dose is 2 mg (0.2 mL) injected SC once daily for 2 weeks. If starting dose is not tolerated, reduce to 1 mg (0.1 mL) once daily. If starting dose is tolerated and additional weight loss is desired, increase the dose to 3 mg (0.3 mL) once daily.

Patients 6 to <12 years of age:

Starting dose is 1 mg (0.1 mL) injected SC once daily for 2 weeks. If starting dose is not tolerated, reduce to 0.5 mg (0.05 mL) once daily. If starting dose is tolerated, increase the dose to 2 mg (0.2 mL) once daily. If the 2 mg once daily dose is tolerated and additional weight loss is desired, the dose may be increased to 3 mg (0.3 mL) once daily.

Evaluate weight loss after 12-16 weeks of treatment. If a patient has not lost at least 5%

of baseline body weight or 5% of baseline BMI for patients with continued growth

potential, discontinue as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

CLINICAL RATIONALE

There is a strong genetic component to human obesity. Most genes that influence an individual’s predisposition to gain weight are not yet known. However, a glimpse into the long-term regulation of body weight has come from studying extreme human obesity caused by single gene defects. These monogenic (single-gene) obesity disorders have confirmed that the hypothalamic leptin-melanocortin system is critical for energy balance in humans because disruption of these pathways causes the most severe obesity phenotypes. Approximately 20 different genes and at least 3 different mechanisms implicated in monogenic causes of obesity have been identified, however, they account for less than 5% of all severe obesity. Monogenic forms of obesity can be divided into three broad categories; the category further discussed in this program is that which is caused by mutations in genes that have a physiologic role in the hypothalamic Leptin-Melanocortin system of energy balance. Obesity due to leptin receptor mutations, proopiomelanocortin mutations, and proprotein convertase mutations will be

addressed further here.2,3

Congenital leptin (LEP) and leptin receptor (LEPR) deficiency are rare, autosomal recessive disorders associated with severe obesity from a very young age (before 2 years). The clinical phenotypes associated with congenital leptin and leptin receptor deficiencies are similar. Patients are born of normal birth weight but exhibit rapid weight gain in the first few months of life resulting in severe obesity. Affected subjects are characterized by intense hyperphagia with food seeking behavior and aggression when food is denied.4

Leptin suppresses food intake in part by acting on hypothalamic neurons expressing POMC. People who are homozygous or compound heterozygous for loss of function mutations in the pro-opiomelanocortin gene, POMC, are hyperphagic and develop early-onset obesity due to loss of melanocortin signaling at the MC4R in the hypothalamus. In the pituitary, POMC is the precursor for adrenocorticotropin (ACTH). As such, POMC deficiency presents in neonatal life with findings of secondary adrenal insufficiency: hypoglycemia, cholestatic jaundice, or other features of adrenal crisis requiring long-term corticosteroid replacement therapy.2,4,5,6 Such children have pale skin, and white Caucasians have red hair, due to the lack of melanocortin function at melanocortin 1 receptors in the skin.2,4,6 The prevalence of POMC is believed to be fewer than 10 patients worldwide.2,3,5

Prohormone convertase-1 (PCSK1, also known as PC1/3) is an enzyme that acts upon a range of substrates including proinsulin, proglucagon, and POMC. Compound heterozygous or homozygous mutations in PCSK1 cause neonatal small bowel enteropathy, glucocorticoid deficiency (secondary to ACTH deficiency), hypogonadotropic hypogonadism and postprandial hypoglycemia due to impaired processing of proinsulin to insulin as well as severe, early onset obesity.4 The prevalence of PCSK1 deficiency is believed to be fewer than 20 patients worldwide.3

Rhythm Pharmaceuticals has started a registry for patients with certain rare genetic disorders of obesity, and their “Uncovering Rare Obesity Program” offers free genetic testing in the United States for patients of all ages.

Efficacy

Setmelanotide is an MC4 receptor agonist with 20-fold less activity at the melanocortin 3 (MC3) and melanocortin 1 (MC1) receptors. MC4 receptors in the brain are involved in regulation of hunger, satiety, and energy expenditure.1,5 In patients with obesity due to POMC, PCSK1, and LEPR deficiency associated with insufficient activation of the MC4 receptor, setmelanotide may re-establish MC4 receptor pathway activity to reduce hunger and promote weight loss through decreased caloric intake and increased energy expenditure.1,6

The safety and efficacy of setmelanotide for chronic weight management in patients with obesity due to POMC, PCSK1, and LEPR deficiency were assessed in 2 identically designed, 1-year, open-label studies, each with an 8-week, double-blind withdrawal period. Study 1 (NCT02896192) enrolled patients aged 6 years and above with obesity and genetically confirmed or suspected POMC or PCSK1 deficiency, and Study 2 (NCT03287960) enrolled patients aged 6 years and above with obesity and genetically confirmed or suspected LEPR deficiency. The studies enrolled patients with bi-allelic, homozygous, or presumed compound heterozygous pathogenic, likely pathogenic variants, or VUS for either the POMC or PCSK1 genes (Study 1) or the LEPR gene (Study 2). Patients with double heterozygous variants in 2 different genes were not eligible for treatment. In both studies, adult patients had a body mass index (BMI) of ≥30 kg/m2.1,7 Weight in pediatric patients was ≥95th percentile using growth chart assessments.1

In Study 1, 80% of patients with obesity due to POMC or PCSK1 deficiency met the primary endpoint, achieving a ≥10% weight loss after 1 year of treatment. In Study 2, 46% of patients with obesity due to LEPR deficiency achieved a ≥10% weight loss after 1 year of treatment.1,7

REFERENCES

  1. Imcivree prescribing information. Rhythm Pharmaceuticals, Inc. November 2020.
  2. Ranadive SA, Vaisse C. Lessons from Extreme Human Obesity: Monogenic Disorders. Endocrinol Metab Clin North Am. 2008 Sep;37(3):733-753.
  3. Huvenne H, Dubern B, Clement K, Poitou C. Rare Genetic Forms of Obesity: Clinical Approach and Current Treatments in 2016. Obes Facts. 2016 Jun;9(3):158-173.
  4. Farooqi IS, O’Rahilly S. The Genetics of Obesity in Humans. [Updated 2017 Dec 23]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279064/.
  5. Low MJ. New Hormone Treatment for Obesity Caused by POMC-Deficiency. Nat Rev Endocrinol. 2016 Sep;12:627-628.
  6. Kuhnen P, Clement K, Wiegand S, et al. Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist. N Engl J Med. 2016;375:240-246.
  7. Clement K, van den Akker E, Argente J, et al. Efficacy and Safety of Setmelanotide, an MC4R Agonist, in Individuals with Severe Obesity due to LEPR or POMC Deficiency: Single-Arm, Open-Label, Multicenter, Phase 3 Trials. Lancet Diabetes Endocrinol. 2020 Dec;8(12):960-970.

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
 
The purpose of pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
 
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

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