Growth Hormones (PG049) Form

Growth hormone (GH) is produced by the pituitary somatotroph cells. GH production begins early in fetal life and continues throughout life, although at a progressively lower rate.

The plan covers treatment for the following FDA-approved indications:

• pediatric patients with growth failure due to any of the following:
• growth hormone (GH) deficiency,
• Turner syndrome,
• Noonan syndrome,
• small for gestational age (SGA),
• Prader-Willi syndrome,
• chronic kidney disease (CKD),
• short stature homeobox-containing gene (SHOX) deficiency
• and adults with childhood-onset or adult-onset GH deficiency.

The plan also covers certain compendial uses for GH including human immunodeficiency, growth failure associated with any of the following:

• cerebral palsy,
• congenital adrenal hyperplasia,
• cystic fibrosis, and
• Russell-Silver syndrome.

All other indications are considered experimental / investigational and are not a covered benefit (including idiopathic short stature).

All requests should be prescribed by or in consultation with one of the following specialties:

• endocrinologist,
• pediatric endocrinologist,
• geneticist, or
• pediatric nephrologist (for CKD only).

Chart documentation and supporting laboratory test results should be provided for review to substantiate medical necessity coverage requests.

The Plan’s preferred growth hormone products are Humatrope (somatropin) and Norditropin (somatropin). Coverage for other (Non-Formulary) growth hormone products are preferred for certain conditions:

• Nutropin AQ (somatropin) is only provided when being prescribed for patients with growth failure associated with Chronic Kidney Disease (CKD).
• Genotropin (somatropin) or Omnitrope (somatropin) is only provided when being prescribed for a patient with Prader-Willi syndrome who is unable to use, or has tried and failed Norditropin (somatropin).

Requests for non-formulary medications are also subject to Medical Necessity Criteria for Non-Formulary Products (PG069) Clinical Guideline.

Table 1: Growth Hormones

Drug | Growth Hormone Deficiency | Turner Syndrome | SGA | Idiopathic Short Stature | Other

Genotropin (Somatropin) | - | Vv | Vv | Vv | PWS

Humatrope (Somatropin) | Vv | - | - | - | SHOX

Norditropin (Somatropin) | - | - | - | - | NS, PWS

NuSpin (Somatropin)

Drug | Growth Hormone Deficiency | Turner Syndrome | SGA | Idiopathic Short Stature | Other

NuSpin (Somatropin) | Vv | - | ae | - | CKD

Omnitrope (Somatropin)

Drug | Growth Hormone Deficiency | Turner Syndrome | SGA | Idiopathic Short Stature | Other

Omnitrope (Somatropin) | - | pv | jv | jv | PWS

Saizen (Somatropin)

Saizen (Somatropin) | - | - | - | - | -

Serostim (Somatropin)

Serostim (Somatropin) | - | - | - | - | HIV

Skytrofa (Lonapegsomatropin-tcgd)

Skytrofa (Lonapegsomatropin-tcgd) | - | - | - | - | -

Sogroya (Somapacitan-beco)

Sogroya (Somapacitan-beco) | - | - | - | - | -

Note: All Growth Hormone medications require prior authorization.

Acronyms:

• CKD = Growth failure due to chronic kidney disease
• HIV = HIV-associated Wasting or Cachexia
• NS = Noonan Syndrome
• PWS = Prader-Willi Syndrome in children
• SBS = Short Bowel Syndrome
• SGA = Growth failure in children born Small for Gestational Age who fail to manifest catch-up growth by age 2 years of age (* – indicated in patients with no catch-up growth by 2 to 4 years of age)
• SHOX = Short stature homeobox-containing gene deficiency

# Discontinued by Manufacturer

Definitions

"Compendia" are summaries of drug information and medical evidence to support decision-making about the appropriate use of drugs and medical procedures. Examples include, but are not limited to:

1. American Hospital Formulary Service Drug Information
2. Clinical pharmacology
3. National Comprehensive Cancer Network Drugs and Biologics Compendium
4. Thomson Micromedex DrugDex
5. United States Pharmacopeia-National Formulary (USP-NF)

"Growth Hormone Deficiency" is a condition characterized by growth failure and can be divided into congenital and acquired forms.

"Noonan Syndrome" is an autosomal dominant condition that is associated with short stature and congenital heart disease (CHD).

"Prader-Willi Syndrome" is a syndrome caused by the absence of expression of the paternally active genes on the long arm of chromosome 15.

"Russell-Silver Syndrome" is a syndrome characterized by severe intrauterine growth restriction and postnatal growth retardation with a prominent forehead, triangular face, downturned corners of the mouth, and body asymmetry (hemihypertrophy).

"Short Stature Homeobox-containing (SHOX) Deficiency" is a syndrome in which there are variants in the SHOX-containing gene on the X chromosome.

"Small for Gestational Age" is defined as a weight and/or length at birth that is at least -2 standard deviations (SD) below the mean for gestational age.

"Turner Syndrome" is a sex chromosome disorder caused by loss of part or all of an X chromosome.

Clinical Indications

Medical Necessity Criteria for Authorization

The Plan considers Growth Hormone medically necessary when ALL the following criteria are met:

1. The medication being requested meets BOTH of the following:
   • is being prescribed for an FDA-approved or compendia supported indication; and
   • is age-appropriate for the member based on FDA approval or is supported by evidence-based compendia; AND
2. The member is unable to use, or has tried and failed the Plan’s preferred growth hormone product(s);

For the treatment of Adult Growth Hormone Deficiency:

Medical Necessity Criteria for Initial Authorization

The Plan considers Growth Hormone medically necessary when BOTH of the following criteria are met:

1. The member has ONE of the following:
   • TWO (2) pre-treatment pharmacologic provocative GH tests demonstrating GH levels less than (<) 5 ng/mL:
     1. unless the agent is Macrilen in which case a GH level of less than (<) 2.8 ng/mL confirms the presence of adult growth hormone deficiency; or
     2. unless the agent is a glucagon in which case a GH level of less than (<) 3 ng/ml confirms the presence of adult growth hormone deficiency;
   • b.

1. ONE (1) pre-treatment pharmacologic provocative GH test demonstrating a GH level less than (<) 5 ng/mL AND a pre-treatment IGF-1 level that is low for age and gender:
   • unless the agent is Macrilen in which case a GH level of less than (<) 2.8 ng/mL confirms the presence of adult growth hormone deficiency; or
   • unless the agent is a glucagon in which case a GH level of less than (<) 3 ng/ml confirms the presence of adult growth hormone deficiency;
2. A structural abnormality of the hypothalamus or pituitary AND BOTH of the following:
   • greater than (>) three (3) documented pituitary hormone deficiencies; and
   • a pre-treatment IGF-1 level that is low for age and gender;
3. A congenital abnormality of the hypothalamus or pituitary (e.g., pituitary transcription factor defects, GH-releasing hormone receptor gene defects) that persist throughout life and was diagnosed in infancy or childhood; AND
4. Chart documentation and supporting lab work are provided for review to substantiate the above-listed requirements.

If the above prior authorization criteria are met, the requested medication will be approved for 12 months.

Medical Necessity Criteria for Reauthorization:

Reauthorization for 12 months will be granted if clinical chart documentation is provided showing the member meets ONE of the following:

1. A clinical improvement, as evidenced by an improvement in the member’s serum IGF-1; OR
2. treatment plan indicating that the GH dose will be increased in response to a low IGF-1 serum concentration

For the treatment of Pediatric Growth Hormone Deficiency:

Medical Necessity Criteria for Initial Authorization

The Plan considers Growth Hormone medically necessary when BOTH of the following criteria are met:

1. The member meets ONE of the following:
   • The member is a neonate or was diagnosed with GH deficiency as a neonate; or
   • The member meets the following clinical parameters:
     1. The member has ONE of the following:
        1. Two (2) pre-treatment pharmacologic provocative GH tests with both results demonstrating a peak GH level less than (<)10 ng/mL; or
        2. A documented pituitary or CNS disorder and a pre-treatment Insulin-like growth factor 1 (IGF-1) level greater than (>) 2 standard deviations (SD) below the mean;
     2. is under 2.5 years of age at initiation of treatment, a pre-treatment height greater than (>) 2 standard deviations (SD) below the mean; or
     3. is above 2.5 years of age at initiation of treatment AND ONE of the following:
        1. a pre-treatment height greater than (>) 2 SD below the mean and a 1-year height velocity greater than (>) 1 SD below the mean; or
        2. a pre-treatment 2-year height velocity greater than (>) 1.5 SD below the mean; or
        3. a pre-treatment 1-year height velocity greater than (>) 2 SD below the mean;
2. Chart documentation and supporting lab work are provided for review to substantiate the above-listed requirements.

If the above prior authorization criteria are met, the requested medication will be approved for 12 months.

Medical Necessity Criteria for Reauthorization:

Reauthorization for 12 months will be granted if clinical chart documentation is provided showing the member meets ALL of the following:

1. a clinical improvement in symptoms since starting the requested medication; AND
2. the member’s epiphyses are open; AND
3. the member's growth rate is greater than (>) 2 cm per year unless there is a documented clinical reason for lack of efficacy (i.e. on treatment less than (<) a year, nearing final adult height).

For the treatment of Turner Syndrome:

Medical Necessity Criteria for Initial Authorization

The Plan considers Growth Hormone medically necessary when ALL of the following criteria are met:

1. The member has a diagnosis of Turner Syndrome confirmed by karyotyping; ANDwn
2. The member's pre-treatment height is less than (<) 5th percentile for age; AND
3. The member's epiphyses are open; AND

Chart documentation and supporting lab work are provided for review to substantiate the above-listed requirements. If the above prior authorization criteria are met, the requested medication will be approved for 12 months.

Medical Necessity Criteria for Reauthorization:

Reauthorization for 12 months will be granted if clinical chart documentation is provided showing the member meets ALL of the following:

1. a clinical improvement in symptoms since starting the requested medication; AND
2. the member’s epiphyses are open; AND
3. the member’s growth rate is greater than (>) 2 cm per year unless there is a documented clinical reason for lack of efficacy (i.e., on treatment less than (<) a year, nearing final adult height).

For the treatment of persons who are/were Small for Gestational Age:

Medical Necessity Criteria for Initial Authorization

The Plan considers Growth Hormone medically necessary when ALL of the following criteria are met:

1. The member meets ONE of the following:
   • Birth weight less than (<) 2500 g at gestational age greater than (>) 37 weeks; or
   • Birth weight or length less than (<) 3rd percentile for gestational age; or
   • Birth weight or length greater than or equal to (>=) 2 SD below the mean for gestational age;
   AND
2. The member’s pre-treatment age is greater than or equal to (>=) 2 years; AND
3. The member failed to manifest catch-up growth (i.e., pre-treatment height greater than or equal to (>=) 2 SD below the mean); AND
4. The member’s epiphyses are open; AND
5. Chart documentation and supporting laboratory test results are provided for review to substantiate the above-listed requirements.

If the above prior authorization criteria are met, the requested medication will be approved for 12 months.

Medical Necessity Criteria for Reauthorization:

Reauthorization for 12 months will be granted if clinical chart documentation is provided showing the member meets ALL of the following:

1. a clinical improvement in symptoms since starting the requested medication; AND
2. the member’s epiphyses are open; AND
3. the member’s growth rate is greater than (>) 2 cm per year unless there is a documented clinical reason for lack of efficacy (i.e., on treatment less than (<) a year, nearing final adult height).

For the treatment of Noonan Syndrome:

Medical Necessity Criteria for Initial Authorization

The Plan considers Growth Hormone medically necessary when ALL of the following criteria are met:

1. The member meets ONE of the following:
   • a pre-treatment height greater than (>) 2 SD below the mean and 1-year height velocity greater than (>) 1 SD below the mean; or
   • a pre-treatment 1-year height velocity greater than (>) 2 SD below the mean;
   AND
2. The member’s epiphyses are open; AND
3. Chart documentation and supporting labwork are provided for review to substantiate the above-listed requirements.

If the above prior authorization criteria are met, the requested medication will be approved for 12 months.

Medical Necessity Criteria for Reauthorization:

Reauthorization for 12 months will be granted if clinical chart documentation is provided showing the member meets ALL of the following:

1. a clinical improvement in symptoms since starting the requested medication; AND
2. the member’s epiphyses are open; AND
3. the member’s growth rate is greater than (>) 2 cm per year unless there is a documented clinical reason for lack of efficacy (i.e., on treatment less than (<) a year, nearing final adult height).

For the treatment of Prader-Willi Syndrome:

Medical Necessity Criteria for Initial Authorization

The Plan considers Growth Hormone medically necessary when BOTH of the following criteria are met:

1. The member has a diagnosis of Prader-Willi Syndrome confirmed by genetic testing showing ONE of the following:
   • deletion in the chromosome 15q11.2-q13 region; or
   • maternal uniparental disomy in chromosome 15; or
   • imprinting defects or translocations involving chromosome 15;
   AND
2. The member's epiphyses are open; AND

Chart documentation and supporting lab work are provided for review to substantiate the above-listedrequirements.If the above prior authorization criteria are met, the requested medication will be approved for 12 months.

Medical Necessity Criteria for Reauthorization:

• Reauthorization for 12 months will be granted if clinical chart documentation is provided showing the membermeeting ONE of the following:
  1. clinical improvement in symptoms since starting the requested medication; OR
  2. stabilization in the member’s body composition and psychomotor function.

For the treatment of SHOX Deficiency:

Medical Necessity Criteria for Initial Authorization

The Plan considers Growth Hormone medically necessary when ALL of the following criteria are met:

1. The member has a diagnosis of SHOX deficiency confirmed by molecular or genetic analyses; AND
2. The member meets ONE of the following:
   • a pre-treatment height greater than (>) 2 SD below the mean and 1 year height velocity is greater than (>) 1 SD below the mean; OR
   • b. a pre-treatment 1-year height velocity greater than (>) 2 SD below the mean; AND
3. The member’s epiphyses are open; AND
4. Chart documentation and supporting lab work are provided for review to substantiate the above-listed requirements.

If the above prior authorization criteria are met, the requested medication will be approved for 12 months.

Medical Necessity Criteria for Reauthorization:

Reauthorization for 12 months will be granted if clinical chart documentation is provided showing the member meets ALL of the following:

1. a clinical improvement in symptoms since starting the requested medication; AND
2. the member’s epiphyses are open; AND
3. the member’s growth rate is greater than (>) 2 cm per year unless there is a documented clinical reason for lack of efficacy (i.e. on treatment less than (<) a year, nearing final adult height).

For the treatment of Growth Failure Associated with CKD, Cerebral Palsy, Congenital Adrenal Hyperplasia, Cystic Fibrosis, or Russell-Silver Syndrome:

Medical Necessity Criteria for Initial Authorization

The Plan considers Growth Hormone medically necessary when ALL of the following criteria are met:

1. The member meets ONE of the following:
   1. is less than (<) 2.5 years of age at initiation of treatment, a pre-treatment height greater than (>) 2 SD below the mean; OR
   2. is greater than or equal to (>) 2.5 years of age at initiation of treatment AND meets ONE of the following:
      1. a pre-treatment height greater than (>) 2 SD below the mean and 1 year height velocity is greater than (>) 1 SD below the mean; OR
      2. a pre-treatment 1-year height velocity greater than (>) 2 SD below the mean; AND
2. The member’s epiphyses are open; AND
3. Chart documentation and supporting lab work are provided for review to substantiate the above-listed requirements.

If the above prior authorization criteria are met, the requested medication will be approved for 12 months.

Medical Necessity Criteria for Reauthorization:

Reauthorization for 12 months will be granted if clinical chart documentation is provided showing the member meets ALL of the following:

1. a clinical improvement in symptoms since starting the requested medication; AND
2. the member’s epiphyses are open; AND
3. the member’s growth rate is greater than (>) 2 cm per year unless there is a documented clinical reason for lack of efficacy (i.e. on treatment less than (<) a year, nearing final adult height).

Experimental or Investigational / Not Medically Necessary

Growth hormone products for any other indications other than those listed under Medical Necessity Criteria for Authorization in this clinical policy are considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

Non-covered indications include, but are not limited to, the following:

• Achondroplasia
• Amyotrophic Lateral Sclerosis (ALS)
• Anorexia Nervosa (AN)
• Ataxia-Telangiectasia (A-T)
• Cognitive Developmental Disorder
• Crohn's Disease (CD)
• Dwarfism
• Eating Disorders
• Female Infertility
• Female Infertility Due to Diminished Ovarian Reserve
• Heart Failure
• Hypophosphatemic Rickets
• Idiopathic Short Stature (ISS)
• Juvenile Idiopathic Arthritis (JIA)
• Lipodystrophies
• Mucopolysaccharidosis IH
• Mucopolysaccharidosis Type I (MPS I)
• Mucopolysaccharidosis Type II (MPS II)
• Mucopolysaccharidosis Type VI
• Non-alcoholic Fatty Liver Disease, NAFLD
• Obesity
• Osteogenesis Imperfecta (OI)
• Osteopenia (Disorder)
• Osteoporosis
• Phelan McDermid Syndrome
• Polycystic Ovarian Syndrome (PCOS)
• Preimplantation Genetic Testing (PGT)
• Primary Disease Fascioscapulohumeral Dystrophy (FSHD)
• Septo-Optic Dysplasia
• Short Bowel Syndrome (SBS)
• Short Stature
• Still's Disease, Juvenile Onset
• Type 1 Diabetes Mellitus

References

1. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update. Endocr Pract, 2003. 9(1): p64-76.
2. Clayton PE, Cianfarani S, Czernichow P, et al. Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab 2007; 92:804.
3. Cohen P, Rogol AD, Deal CL, et al, "Consensus Statement on the Diagnosis and Treatment of Children With Idiopathic Short Stature: A of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop," J Clin Endocrinol Metab, 2008, 93(11):4210-7.
4. Collett-Solberg PF, Ambler G, Backeljauw PF, et al. Diagnosis, genetics, and therapy of short stature in children: a Growth Hormone Research Society International perspective. Horm Res Paediatr. 2019;92(1):1-14.
5. Cook DM, Yuen KC, Biller BM, Kemp SF, Vance ML; American Association of Clinical Endocrinologists (AACE). American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update. Endocr Pract. 2009;15(suppl 2):S1-S29.
6. de Boer H, Blok GJ, Popp-Snijders C, et al. Monitoring of growth hormone replacement therapy inadults, based on measurement of serum markers. J Clin Endocrinol Metab 1996; 81:1371.
7. Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(11):3888-3921. doi:10.1210/jc.2016-2118.
8. Genotropin (somatropin) [prescribing information]. New York, NY: Pharmacia & Upjohn Co; April 2019.
9. Genotropin MiniQuick (somatropin) [prescribing information]. New York, NY: Pharmacia & Upjohn Co; April 201 9. Genotropin MiniQuick (somatropin) [prescribing information]. New York, NY: Pharmacia & Upjohn Co; April 2019.
10. Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361-397. doi:10.1159/000452150
11. Humatrope (somatropin) [prescribing information]. Indianapolis, IN: Lilly USA LLC; October 2019.
12. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML; Endocrine Society (ES). Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587-1609.
13. Ngenla (somatrogon) [prescribing information]. New York, NY: Pfizer Labs; June 2023.
14. Norditropin (somatropin) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; February 2018.
15. Nutropin AQ (somatropin) [prescribing information].

1. Nutropin AQ (somatropin) [prescribing information]. South San Francisco, CA: Genentech; December 2016.
2. Nutropin AQ NuSpin (somatropin) [product monograph]. Mississauga, Ontario, Canada: Hoffmann-La Roche Limited; June 2018.
3. Omnitrope (somatropin) [prescribing information]. Princeton, NJ: Sandoz Inc; June 2019.
4. Russell-Silver Syndrome - National Organization for Rare Diseases, 9th edition. 2020. Available at:https://rarediseases.org/rare-diseases/russell-silver-syndrome/
5. Saizen (somatropin) [prescribing information]. Rockland, MA: EMD Serono Inc; February 2020.
6. Serostim (somatropin) [prescribing information]. Rockland, MA: EMD Serono Inc; June 2019.
7. Skytrofa (lonapegsomatropin-tcgd) [prescribing information]. Palo Alto, CA: Ascendis Pharma Inc; August 2021.
8. Sogroya (somapacitan-beco) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; April 2023.
9. Yuen KCJ, Biller BMK, Radovick S, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Growth Hormone Deficiency in Adults and Patients Transitioning from Pediatric to Adult Care. AACE Guidelines, Nov 2019. 25(11): p1191-1232. DOI: https://doi.org/10.4158/GL-2019-0405
10. Zomacton (somatropin) [prescribing information]. Parsippany, NJ: Ferring Pharmaceuticals; July 2018.
11. Zomacton [package insert]. Parsippany, NJ: Ferring Pharmaceuticals Inc.; July 2018.
12. Zorbtive (somatropin) [prescribing information]. Rockland, MA: EMD Serono Inc; September 2019.
13. Clinical Guideline Revision / History Information Original Date: 08/06/2020 Reviewed/Revised: 06/24/2021, 12/01/2021, 06/23/2022, 9/15/2022, 9/21/2023