Mecasermin; recombinant human insulin-like growth factor-1 (Increlex™)
Mecasermin may be considered medically necessary for its FDA-approved indication for the treatment of growth failure in children. (See Policy Guidelines for criteria.)
Use of mecasermin to treat all other indications is considered investigational, including but not limited to:
The use of Mecasermin for idiopathic short stature is considered not medically necessary.
Note: Policy and guidelines for the use of growth hormone (somatropin) are contained in a separate medical policy. (See Related Policies)
Coverage may be reauthorized for up to 12 months in patients previously receiving mecasermin if ALL the following criteria are met:
Mecasermin is produced by recombinant DNA technology and has an identical amino acid sequence to endogenous human insulin-like growth factor-1 (IGF-1). Mecasermin is approved for the treatment of growth failure in children with severe primary IGF-1 deficiency (growth hormone receptor mutations, post-growth hormone receptor signaling pathway mutations, or IGF-1 gene defects) and in those with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. It is estimated that 30,000 to 60,000 children in the US and Western Europe have primary IGF-1 deficiency. Of these individuals, approximately 20%, or 6,000 to 12,000, have severe primary IGF-1 deficiency.
The current somatomedin hypothesis of statural growth involves GH release by the anterior pituitary that is controlled in a stimulatory fashion by GH-releasing hormone and in an inhibitory fashion by somatostatin. Circulating GH then binds to GH receptors in the liver resulting in production of IGF-1, IGF binding proteins, and acid labile subunit. Virtually all circulating IGF-1 is bound to IGF binding proteins and acid labile subunit. This tertiary complex reduces extravascular passage and increases the half-life of IGF-1. Circulating IGF-1 then stimulates multiple processes leading to statural growth and metabolic changes that support this growth. GH also stimulates prechondrocyte differentiation and local production of IGF-1 (autocrine and paracrine) that in turn stimulate clonal expansion, maturation of chondrocytes, and growth. Approximately 15% to 20% of growth is thought to be the result of this local effect of GH versus that resulting from circulating hepatic IGF-1.
Mecasermin is not a substitute for GH treatment and is not indicated for the treatment of secondary IGF deficiency resulting from GH deficiency, malnutrition, hypothyroidism or chronic corticosteroid therapy.
Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply. This medical policy does not apply to Medicare Advantage.
Mecasermin may be covered under the drug or medical benefit.
Severe primary IGF-1 deficiency or GH gene deletion with neutralizing antibodies to GH are rare disorders currently without therapeutic alternatives. A small quantity of low quality evidence consistently supports the efficacy and safety of mecasermin for the treatment of children with these conditions to increase statural growth. According to the FDA review report for mecasermin, approval was granted based on four small (n= 6 to 23) and one long-term clinical studies (4 open-label and 1 double-blind placebo-controlled). Because of the rarity of severe primary IGF-1 deficiency, the patients and data from the 4 smaller studies were “rolled into” the larger long-term study.
Chernausek et al. reported long-term efficacy and safety results from a multicenter, open-label, uncontrolled study in 76 children with severe IGF-1 deficiency associated with growth hormone insensitivity. It should be noted that the inclusion criteria used for the study were less stringent than defined by the FDA for identification of patients with severe deficiency. A total of 76 patients initially received mecasermin 0.04-0.08 mg/kg SC twice daily, and if the dose was tolerated for at least a week without hypoglycemic episodes it was titrated by 0.04 mg/kg/dose to 0.12 mg/kg twice daily. The primary study endpoint was change from baseline in height velocity. During the first year of treatment, height velocity increased from a mean baseline of 2.8 cm/yr to 8.0 cm/yr, in 59 evaluable patients (P<0.0001). Height velocity was lower in subsequent years, but remained above baseline for up to 8 years. Height velocity was dose dependent or fastest in those receiving the maximal dose (0.012 mg/kg twice daily). Bone age increased modestly an average of 5.8 yrs over 5.1 years (P=0.01).
A smaller (n=8) open-label uncontrolled study in which patients with severe primary IGF-1 deficiency were treated with mecasermin 0.08-0.12 mg/kg twice daily as tolerated for up to 7.5 years showed similar results. During the first year of treatment, height velocity increased from a mean baseline of 4.0 cm/yr to 9.3 cm/yr (mean height velocity SDS +3.8) and 6.2 cm/yr (mean height velocity SDS +0.5) in the second year of treatment. Mean change in height velocity SDS was +1.4 after 6-7 years of therapy.
The most commonly reported adverse events reported with use of mecasermin at recommended doses in children with severe primary IGF-1 deficiency were hypoglycemia, lymphoid tissue hypertrophy, and injection-site lipohypertrophy. Hypoglycemia was minimized by consumption of a meal or a snack within 20 minutes of administration of the drug, and lipohypertorphy was minimized by rotation of the injection site with each dose. Rarely, intracranial hypertension was also reported.
Labeled contraindications include closed epiphyses, suspected or active neoplasia, intravenous (IV) administration, and hypersensitivity to any component. Labeled warnings and precautions include that the product contains benzyl alcohol as a preservative, which has been associated with neurological toxicity in neonates; sensitivity reactions have been reported; treatment should be directed by physicians experienced in the diagnosis and management of patients with growth disorders; mecasermin should be administered shortly (± 20 min) before or after a meal or snack because mecasermin has insulin-like hypoglycemic effects; hypertrophy of lymphoid tissue with complications (e.g., snoring, sleep apnea) has been observed; intracranial hypertension has been reported; rapid growth may cause slipped capital femoral epiphysis or worsen scoliosis; and allergic reactions have been reported.
The recommended starting dose of mecasermin is 0.04-0.08 mg/kg subcutaneously twice daily. If well-tolerated (without hypoglycemia) for at least one week, the dose may be increased in 0.04 mg/kg/dose increments up to the maximum dose of 0.12 mg/kg SC twice daily. Doses greater than 0.12 mg/kg twice daily have not been studied in children with primary IGF-1 deficiency and should not be used to avoid potential hypoglycemia.
A literature search of the MEDLINE database conducted from August 2008 through June 2009 did not identify any additional published studies that would prompt reconsideration of the policy statements.
A literature search of the MEDLINE database conducted from July 2009 through April 2010 did not identify any additional published studies that would prompt reconsideration of the policy statements.
A literature search of the MEDLINE database conducted from May 2010 through January 2011 did not identify any additional published studies that would prompt reconsideration of the policy statements.
A literature search of the MEDLINE database conducted from January 2011 through February 2012 did not identify any additional published studies that would prompt reconsideration of the policy statements.
A literature search of the MEDLINE database conducted from January through December 2012 did not identify any additional published studies that would prompt reconsideration of the policy statements.
A literature search conducted from January 2013 through February 2014 found no new evidence that would change this policy.
Injection, Mecasermin (Increlex™), 1 mg
Type of Service
Retail pharmacy self-administered subcutaneous injectable
Add to Prescription Drug Section - New PR Policy.
Replace Policy - Policy updated with literature search, no change to the policy statement.
Replace Policy - Policy updated with literature search, no change to the policy statement.
Replace Policy - Policy updated with literature review; no change in policy statement. Policy guidelines updated for improved clarity and administrative simplicity.
Replace policy. Policy updated with literature review; policy statements unchanged. Reference 15 added.
Replace policy. Policy updated with literature review; policy statements unchanged.
Annual review. Policy updated with literature review; policy statements unchanged.
Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).