Growth Hormones – NC Standard

Restricted Product(s)

Preferred

• Genotropin®, Genotropin MiniQuick® (somatropin) 
• Omnitrope® (somatropin)

Non-Preferred

• Humatrope®(somatropin) 
• NgenlaTM (somatrogon-ghla) 
• Norditropin®,Nordiflex®, Norditropin Flexpro® (somatropin) 
• Nutropin AQ® NuSpinTM (somatropin) 
• Saizen® (somatropin) 
• Serostim® (somatropin) 
• Sogroya® (somapacitan-beco) 
• Skytrofa® (lonapegsomatropin) 
• Zomacton® (somatropin)

FDA Approved Use

• For the treatment of pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone (GH), short stature associated with Noonan syndrome, short stature associated with Turner syndrome, short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years, Idiopathic Short Stature (ISS), and growth failure due to Prader-Willi Syndrome. 
• For the replacement of endogenous growth hormone (GH) in adults with growth hormone deficiency.

Coverage Note

The use of GH for short stature in patients with no proven GH deficiency (e.g., idiopathic short stature without evidence of biologic impairment of the growth hormone pituitary axis) is not covered. It is considered cosmetic.

Criteria for Approval of Restricted Product(s)

Initial Coverage Criteria

1. The request is for Humatrope, Ngenla, Norditropin, Nordiflex, Norditropin Flexpro, Nutropin AQ NuSpin, Saizen, Serostim, Skytrofa, Sogroya, or Zomacton; AND
   1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the preferred products (e.g., Omnitrope or Genotropin) (medical record documentation required); AND 
      1. The patient has an FDA labeled contraindication to ALL of the preferred products (e.g.,Omnitrope or Genotropin) (medical record documentation required); OR 
      2. The provider has submitted a written, clinical rationale as to why the patient cannot safely use the preferred product (e.g.,Omnitrope or Genotropin) (medical record documentation required); AND
2. The patient is less than 18 years of age with open epiphyses; AND 
   1. The patient does NOT have idiopathic short stature without evidence of biologic impairment of the growth hormone pituitary axis; AND 
   2. The patient has growth failure due to inadequate secretion of GH, as documented by failure of at least one GH stimulation test (e.g., L-dopa, clonidine, glucagon, propranolol, arginine, or insulin challenge test); AND 
      1. The patient has serial height/length and weight records showing linear growth failure, and is persistently under the 3rd percentile (i.e., > 1.88 SD below mean for age and sex) in height; OR 
      2. The patient has significant growth deceleration and a history of CNS pathology or brain irradiation; OR 
      3. The patient is a neonate with hypoglycemia and GH deficiency (one abnormal GH test is sufficient for hypoglycemic neonates in whom GH deficiency is suspected); OR 
   3. The patient did NOT fail a growth hormone (GH) stimulation test but are identified to have biochemical abnormalities in the growth hormone metabolic pathway; AND 
      1. The patient is persistently below the 1.2 percentile in height, (2.25 SD below the mean for age & sex or > 2 SD below the midparental height percentile); AND 
      2. The patient’s growth velocity is < 25th percentile for bone age; AND 
      3. The patient’s bone age is > 2 SD below the mean for age; AND 
      4. The patient has low serum insulin-like growth factor 1 (IGF-1, also called Somatomedin C) AND/OR insulin-like growth factor binding protein 3 (IGFBP3).
         ***Children whose height is >3.0 SD below age-matched mean and whose IGF-1 levels are also >3 SD below mean may be diagnosed with primary IGF-1 deficiency. See policy, Treatment for Severe Primary IGF-1 Deficiency; OR 
   4. The patient is female with Turner Syndrome; AND 
      1. The patient is under the 5th percentile in height; OR 
   5. The patient has growth failure due to Prader-Willi Syndrome (PWS) or Noonan Syndrome; OR 
   6. The patient has SHOX (short stature homeobox-containing gene) deficiency; AND 
      1. The patient is persistently under the 3rd percentile (i.e., > 1.88 SD below mean for age and sex) in height; OR 
   7. The patient was born small for gestational age (SGA) or with intrauterine growth retardation (IUGR); AND 
      1. The birth weight and/or length were more than 2 standard deviations (SD) below the mean for the gestational age; AND
      2. The patient has failed to show catch-up growth by age 2 (defined as a height velocity below 1 SD score, adjusted for age); OR
   8. The patient has chronic kidney disease (CKD) (defined as GFR of < 75 ml/min/1.73m2) resulting in short stature (i.e., persistently under 3rd percentile in height); AND 
      1. The patient is NOT within 1 year of a kidney transplant; OR 
   9. The product will be used for a patient that received growth hormone while hospitalized for 3 rd degree burns with observed growth delays; AND
      1. The patient is within 1 year of discharge from hospitalization; OR
3. The patient is 18 years of age or older; AND 
   1. The patient has childhood onset symptomatic GH deficiency, where persistent GH deficiency is documented by at least one failed GH stimulation test performed at least 3 months after the cessation of prior GH therapy; OR 
   2. The patient has adult-onset symptomatic GH deficiency associated with low GH levels (documented by failure of at least two GH stimulation tests). Please Note: 24-hour continuous measurements of GH, serum levels of IGF-1, or serum levels of IGFBP-3 are considered inadequate to document GH deficiency; OR 
   3. The patient has adult-onset symptomatic GH deficiency associated with multiple hormone deficiencies (i.e., panhypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery radiation therapy, or trauma, defined as: 
      1. The patient has at least two documented additional hormone deficiencies (other than GH) requiring hormone replacement therapy (e.g., TSH, ACTH, ADH or gonadotropin hormones) as well as failure of at least 1 GH stimulation test; OR 
      2. The patient has at least three pituitary hormone deficiencies (other than GH) requiring hormone replacement therapy (where clinically appropriate) are documented; AND 
         1. The patient has a low IGF-1 level (below 80 ng/ml) documented in lieu of GH stimulation testing; OR 
4. The patient has been diagnosed with HIV cachexia or "wasting syndrome"; AND 
   1. The patient is on optimal antiretroviral therapy; AND 
   2. The patient has unintentional weight loss of at least 10% of baseline weight; OR 
      1. BMI < 20 kg/m2, not attributable to other causes (such as AIDS-associated diarrhea, infection, malignancy or depression): OR 
5. The patient has been diagnosed with Short Bowel Syndrome (SBS) due to surgical or functional loss of small bowel; AND
   1. The patient requires parenteral (intravenous) nutrition supplementation at least 5 days/week for a total of at least 3,000 calories/week; OR 
6. Indications outside of FDA labeling will be subject to medical necessity review in accordance with specific strong endorsement or support by nationally recognized compendia, when such recommendation is based on strong/high levels of evidence, and/or uniform consensus of clinical appropriateness has been reached. Medical records and references / evidence must be provided; AND
7. For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies.

Duration of Approval: determined by indication (see below)
Short bowel syndrome: 90 days (3 months)
Children who do not fail stimulation tests, but have biochemical abnormalities: 180 days (6 months)
Adult growth hormone deficiency: 365 days (1 year)
Others: 365 days (1 year)

Continuation Coverage Criteria

1. The patient has been previously approved with Blue Cross and Blue Shield of North Carolina (Blue Cross NC) or would have met initial criteria for approval upon the start of therapy; AND 
   1. The request is for Humatrope, Ngenla, Norditropin, Nordiflex, Norditropin Flexpro, Nutropin AQ NuSpin, Saizen, Serostim, Skytrofa, Sogroya, or Zomacton; AND 
      1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the preferred products (e.g.,Omnitrope or Genotropin) (medical record documentation required); AND 
         1. The patient has an FDA labeled contraindication to ALL of the preferred products (e.g., Omnitrope or Genotropin) (medical record documentation required); OR 
         2. The provider has submitted a written, clinical rationale as to why the patient cannot safely use the preferred product (e.g.,Omnitrope or Genotropin) (medical record documentation required); AND 
2. The patient is less than 18 years of age; AND 
   1. The patient has an increase in growth velocity over pre-treatment level > 50 percent; AND 
   2. The patient has an annual growth velocity in response to therapy calculated to be > 4.5 cm/year in a pre-pubertal child or > 2.5 cm/yr in a post-pubertal child; AND 
   3. Expected final adult (estimated mid-parental) height has not been achieved; AND 
   4. Epiphyses have not closed. Epiphyseal closure is defined as a bone age of 16 years in a male or 14 years in a female on wrist films. Note: Wrist films for bone age must be obtained annually for renewal submission for girls > 10 years old and boys > 12 years old; AND 
   5. For patients that received growth hormone while hospitalized for 3 rd degree burns with observed growth delays, the patient is within 1 year of hospitalization; OR 
3. The patient is using for HIV cachexia; AND
   1. The patient has not recovered their baseline weight; OR 
   2. The patient’s BMI < 20 kg/m2; OR 
4. The patient is using for Short Bowel Syndrome (SBS); AND 
   1. The patient has sustained a decrease in IV nutritional requirements while maintaining or increasing weight; OR 
5. The patient is using for adult growth hormone deficiency and continues to see clinical benefit. 

Duration of Approval: determined by indication (see below)

Short bowel syndrome: 90 days (3 months)
Children who do not fail stimulation tests, but have biochemical abnormalities: 180 days (6 months)
Adult growth hormone deficiency: 365 days (1 year)
Others: 365 days (1 year)

References

All information referenced is from FDA package insert unless otherwise noted below.

Aili Low JF, Barrow RE, Mittendorfer B, et al. The effect of short-term growth hormone treatment on growth and energy expenditure in burned children. Burns 2001; 27:447.

Jeschke MG, Herndon DN, Wolf SE, et al. Recombinant human growth hormone alters acute phase reactant proteins, cytokine expression, and liver morphology in burned rats. J Surg Res 1999; 83:122.

Policy Implementation/Update Information

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q1 annually.

October 2024: Criteria update: Remove HumatroPen, Nutropin, and Zorbitive due to products been unavailable.
April 2024: Criteria change: Removed Norditropin from preferred products. Genotropin and Omnitrope remain preferred products.
January 2024: Criteria update: Format Update.
December 2023: Criteria change: Added Omnitrope as a preferred product in addition to Norditropin and Genotropin. Removed medical record requirements. Added the patient does NOT have idiopathic short stature without evidence of biologic impairment of the growth hormone pituitary axis criteria point.
August 2023: Criteria update: Added new to market Ngenla to policy.
July 2023: Criteria change: Updated continuation criteria to require t/f of preferred products for all reviews.
May 2023: Criteria update: Added new to market Sogroya to policy.
March 2023: Criteria update: Clarified Genotropin and Genotropin MiniQuick listed in restricted products vs Genotropin alone.
January 2023: Criteria change: Criteria review and formatting changes. Addition of preferred product Genotropin to already preferred products Norditropin/Nordiflex.
October 2021: Criteria update: Added new to market Skytrofa to policy. Duration of approval changed to 365 days for adult growth hormone deficiency.
January 2020: Criteria Change: removed coverage for adult burn victims due to lack of FDA approval and safety concerns; changed preferred products from Omnitrope to Norditropin/Nordiflex products; limited medical record documentation to GH stimulation tests and evidence of limited growth; reformatted criteria.
January 2018: Added additional medical record documentation requirements
January 2017: Reviewed for ASO Net Results and Essential formularies; non- formulary verbiage added.
October 2016: Annual review; No change.
June 2015: Historical revision.