Prior authorization is recommended. To authorize, call Blue Cross and Blue Shield of Montana (BCBSMT) Customer Service at 1-800-447-7828 or fax your request to the Medical Review Department at 406-441-4624. A retrospective review will be performed if services are not prior authorized.
- Height standard deviation score £ 3.0, AND
- Basal IGF-1 standard deviation score £ 3.0, AND
- Normal or elevated growth hormone (GH) level.
BCBSMT may consider mecasermin recombinant (Increlex™) medically necessary for the treatment of growth failure in children with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.
BCBSMT considers all other uses of mecasermin recombinant (Increlex™) experimental, investigational and unproven, including but not limited to the treatment of:
- GH deficiency (such as Prader-Willi, Russell-Silver, Noonan, or Turner’s syndromes),
- Short stature due to unknown cause (idiopathic short stature),
- Cystic fibrosis,
- Extreme insulin resistance,
- Chronic treatment with pharmacologic doses of anti-inflammatory steroids,
- Myotonic muscular dystrophy (MMD),
- Amyotrophic lateral sclerosis (ALS),
- Human immunodeficiency virus- (HIV-) associated adipose redistribution syndrome (HARS) and/or acquired immunodeficiency syndrome- (AIDS-) wasting,
- Adults with IGF-1 deficiency, OR
- Retinopathy of prematurity (ROP) in premature neonates.
NOTE: Iplex™ has been discontinued and is no longer on the market.
NOTE: See Description for recommended FDA labeled dosing.
Federal mandate prohibits denial of any drug, device, or biological product fully approved by the FDA as investigational for the Federal Employee Program (FEP). In these instances coverage of these FDA-approved technologies are reviewed on the basis of medical necessity alone. Call the BCBSMT FEP Customer Service Department at 1-800-634-3569 for benefit information.
Rationale for Benefit Administration
This medical policy was developed through consideration of peer reviewed medical literature, FDA approval status, accepted standards of medical practice in Montana, Technology Evaluation Center evaluations, and the concept of medical necessity. BCBSMT reserves the right to make exceptions to policy that benefit the member when advances in technology or new medical information become available.
The purpose of medical policy is to guide coverage decisions and is not intended to influence treatment decisions. Providers are expected to make treatment decisions based on their medical judgment. BCBSMT recognizes the rapidly changing nature of technological development and welcomes provider feedback on all medical policies.
When using this policy to determine whether a service, supply or device will be covered, please note that member contract language will take precedence over medical policy when there is a conflict.
According to the manufacturer, it is estimated that 6,000 children in the United States would meet the criteria for coverage using mecasermin. The FDA approval was based on five studies enrolling a total of 71 patients. The primary outcomes included changes in height velocity, height velocity standard deviation scores (SDS), and height SDS over a period of eight years. However, only 13 subjects were followed for the maximum eight-years, and only 58 of the 71 had baseline height velocity data. Height velocity increased in the first year, on average, to 8.0 cm per year from a baseline height of 2.8 cm per year, nearly tripling the rate of growth (P<0.0001). In years two through six, height velocity was sustained at approximately 5.0 cm per year. Change in bone age was appropriate for chronological age. No final height data was available (FDA, 2005; BCBSA TEC Clearinghouse News, 2006).
In clinical studies of 71 subjects with primary insulin-like growth factor-1 (IGF-1) deficiency (IGFD) treated for a mean duration of 3.9 years and representing 274 subject-years, no subjects withdrew from any clinical study because of adverse events. Mecasermin has not been studied in children less than two years of age or in adults (FDA, 2005; BCBSA TEC Clearinghouse News, 2006).
Since the last update, additional information was added regarding the new orphan product designation from the FDA approval of mecasermin rinfabate. The FDA based their decision on a study of 36 children and adolescents with primary insulin-like growth factor-1 deficiency (IGFD). Subjects were enrolled in the clinical trial on the basis of extremely short stature, low IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3) serum concentrations and normal GH secretion. The subjects were divided into two cohorts treated sequentially. Cohort #1 (n=19) were treated for the first 12 months, evaluated at month six and 12, being given up to 1 mg/kg daily. Cohort #2 (n=17) were evaluated for efficacy at month six after treatment with up to 2 mg/kg daily. For both cohorts, height velocity increased. For Cohort #1 subjects at month six, the height velocity increased by 8.1 cm and then increased an additional 6.3 cm at one year. While on a higher dose level, Cohort #2 subjects had a mean height velocity of 9.1 cm at month six (FDA, 2009).
There have been no studies to date comparing the efficacy of Increlex to Iplex. According to the literature, mecasermin may have the potential for off-label use in conditions other than severe primary IGFD (Williams, 2008).
Insmed Inc., manufacturer of Iplex, has begun pursuing separate Phase II studies focusing on treatment of both myotonic muscular dystrophy (MMD) and amyotrophic lateral sclerosis (ALS). This is in addition to investigating retinopathy of prematurity (ROP) in premature neonates, via a Material Transfer Agreement with Premacure AB Biopharmaceuticals (Insmed Inc., 2008).
A search of peer reviewed literature and FDA labeling through March 2012 identified no new clinical trial publications or any additional information that would change the Increlex coverage position of this medical policy. Iplex has been discontinued from marketing based on costs of manufacturing and has been removed from the medically necessary indications of this medical policy (Insmed Inc., 2009).
Disclaimer for coding information on Medical Policies
Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.
The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.
Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.