hGH analogs: somapacitan-beco (Sogroya®)Recombinant hGH (rhGH) formulations: somatropin (Genotropin®, Humatrope®, Norditropin®, Nutropin AQ® NuSpin®, Omnitrope®, Saizen®, Serostim®, Zomacton®, Zorbtive®) Form

The following human growth hormone (hGH) formulations require prior authorization: • hGH analogs: somapacitan-beco (Sogroya®), somatrogon-ghla (Ngenla™) • Recombinant hGH (rhGH) formulations: somatropin (Genotropin®, Humatrope®, Norditropin®, Nutropin AQ® NuSpin®, Omnitrope®, Saizen®, Serostim®, Zomacton®, Zorbtive®) Drugs Children GHD GF Sogroya GF Genotropin GF Humatrope GF Ngenla Norditropin GF GF NutropinAQ NuSpin Omnitrope Saizen Serostim Zomacton Zorbtive GF GF GF PWS TS NS SHOX CKD SGA ISS GF GF GF GF SS SS GF GF SS SS/GF SS GF GF SS SS GF GF SS/GF SS GF GF SS SS SS Adults GHD HIV SBS X X X X X X X X X X Abbreviations: CKD: chronic kidney disease, GF: growth failure, GHD: growth hormone deficiency, HIV: human immunodeficiency virus, ISS: idiopathic short stature, NS: Noonan syndrome, PWS: Prader-Willi syndrome, SBS: short bowel syndrome, SGA: small for gestational age, SHOX: short stature homeobox-containing gene, SS: short stature, TS: Turner syndrome FDA Approved Indication(s) hGH Analogs: Sogroya is indicated for: • Treatment of pediatric patients aged 2.5 years and older who have GF due to inadequate secretion of endogenous GH • Replacement of endogenous GH in adults with GHD Ngenla is indicated for: • Treatment of pediatric patients aged 3 years and older who have GF due to inadequate secretion of endogenous GH Page 1 of 20

CLINICAL POLICY
Human Growth Hormone rhGH Formulations: Genotropin is indicated for treatment of:
• Children with GF due to GHD, PWS, SGA, TS, and ISS. • Adults with either childhood-onset (CO) or adult-onset (AO) GHD. Humatrope is indicated for treatment of:
• Pediatric patients: GF due to inadequate secretion of endogenous GH; SS associated with TS; ISS, high standard deviation score (SDS) <- 2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range; SS or GF in SHOX deficiency; SS born small for SGA with no catch-up growth by 2 years to 4 years of age.
• Replacement of endogenous GH in adults with GHD. Norditropin FlexPro is indicated for the treatment of: • Children with GF due to GHD, SS associated with NS, SS associated with TS, SS born SGA with no catch-up growth by age 2 to 4 years, ISS, and GF due to PWS. • Replacement of endogenous GH in adults with GHD. Nutropin AQ NuSpin is indicated for the treatment of: • Children with GF due to GHD, ISS, TS, and CKD up to the time of renal transplantation.
• Adults with either CO or AO GHD. Omnitrope is indicated for the treatment of: • Children with GF due to GHD, PWS, SGA, TS, and ISS. • Adults with either CO or AO GHD. Saizen is indicated for: • Children with GF due to GHD. • Adults with either CO or AO GHD. Serostim is indicated for the treatment of: • HIV patients with wasting or cachexia to increase lean body mass and body weight, and improve physical endurance. Zomacton is indicated for: • Treatment of pediatric patients who have GF due to inadequate secretion of endogenous GH, SS associated with TS, ISS, SS or GF in SHOX deficiency, and SS born SGA with no catch- up growth by 2 years to 4 years. • Replacement of endogenous GH in adults with GHD. Zorbtive is indicated for treatment of: • SBS in adult patients receiving specialized nutritional support.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
Page 2 of 20

CLINICAL POLICY
Human Growth Hormone Index I. Initial Approval Criteria A. Growth Hormone Deficiency with Neonatal Hypoglycemia (off-label) B. Growth Hormone Deficiency with Short Stature/Growth Failure - Children (open epiphyses) C. Genetic Disorders with Short Stature/Growth Failure - Children D. Chronic Kidney Disease with Growth Failure - Children E. Born Small for Gestational Age with Short Stature/Growth Failure - Children F. Idiopathic Short Stature - Children G. Growth Hormone Deficiency - Adults and Transition Patients (closed epiphyses) H. Short Bowel Syndrome - Adults I. HIV-Associated Wasting/Cachexia - Adults J. Other diagnoses/indications II. Continuing Approval Criteria A. All Pediatric Indications (open epiphyses) B. Growth Hormone Deficiency - Adults and Transition Patients (closed epiphyses) C. Short Bowel Syndrome - Adults D. HIV-Associated Wasting/Cachexia - Adults E. Other diagnoses/indications III. Diagnoses/Indications for which coverage is NOT authorized:
IV. Appendices V. Dosage and Administration VI. Product Availability VII. References It is the policy of health plans affiliated with Centene Corporation® that Sogroya, Ngenla, and somatropin are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Growth Hormone Deficiency with Neonatal Hypoglycemia (off-label) (must meet all):

1. Diagnosis of neonatal hypoglycemia due to GHD;
2. Request is for a somatropin formulation;
3. Prescribed by or in consultation with a pediatric endocrinologist;
4. Age ≤ 1 month;
5. Serum GH concentration ≤ 5 µg/L;
6. Member meets one of the following (a or b): a. Imaging shows hypothalamic-pituitary abnormality; b. Deficiency of ≥ 1 anterior pituitary hormone other than GH (e.g., ACTH, TSH, LH, FSH, prolactin);
   7. The requested product is not prescribed concurrently with Increlex® (mecasermin);

7. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
   a. Member must use Norditropin and Humatrope; Page 3 of 20

   CLINICAL POLICY
   Human Growth Hormone b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope vial, unless contraindicated or clinically significant adverse effects are experienced;
   c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Norditropin, Humatrope, and Omnitrope

   9. Dose does not exceed 0.30 mg/kg per week. Approval duration: 6 months B. Growth Hormone Deficiency with Short Stature/Growth Failure - Children (open epiphyses) (must meet all):
8. Diagnosis of GHD;
9. Prescribed by or in consultation with a pediatric endocrinologist;
10. Age < 18 years;
11. If request is for Sogroya, age ≥ 2.5 years;
12. If request is for Ngenla, age ≥ 3 years;
13. If age > 10 years, open epiphysis on x-ray;
14. Member meets one of the following (a or b): a. Low insulin-like growth factor (IGF)-I serum level; b. Low insulin-like growth factor binding protein (IGFBP)-3 serum level;
    8. Member meets one of the following (a, b, c, d, or e):
       a. Two GH stimulation tests with peak serum levels ≤ 10 µg/mL (e.g., stimulants: arginine, clonidine, glucagon); b. Deficiency of ≥ 3 pituitary hormones (i.e., ACTH, TSH, LH, FSH, prolactin); c. Prior surgery or radiotherapy to the hypothalamic-pituitary region;
       d. Imaging shows hypothalamic-pituitary abnormality;
       e. GHD-specific mutation (e.g., POU1F1, PROP1, LHX3, LHX4, HESX1, OTX2, TBX19, SOX2, SOX3, GLI2, GHRHR, GH1);
    9. Member meets one of the following (a or b): a. SS: height is > 2 SD below the mean for age and sex (SD, height, date, and age in months within the last 90 days are required); b. GF: one of the following (i, ii, or iii): i. Height deceleration across two growth chart percentiles representing > 1 SD below the mean for age and sex (SD and 2 heights, dates, and ages in months at least 6 months apart within the last year are required); ii. Growth velocity > 2 SD below the mean for age and sex over 1 year (SD and 2 heights, dates, and ages in months at least 1 year apart within the last year are required); iii. Growth velocity > 1.5 SD below the mean for age and sex sustained over 2 years (SD and 2 heights, dates, and ages in months at least 2 years apart within the last two years are required);
    10. The requested product is not prescribed concurrently with Increlex (mecasermin);

15. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
    a. Member must use Norditropin and Humatrope; Page 4 of 20

    CLINICAL POLICY
    Human Growth Hormone b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope* vial, unless contraindicated or clinically significant adverse effects are experienced;
    c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced;

    • Prior authorization may be required for Norditropin, Humatrope, and Omnitrope 12. Dose does not exceed one of the following (a, b, or c): a. For Ngenla: 0.66 mg/kg per week; b. For Sogroya: 0.16 mg/kg per week; c. For somatropin agents: 0.30 mg/kg per week. Approval duration: 6 months C. Genetic Disorders with Short Stature/Growth Failure - Children (must meet all):
16. Diagnosis of PWS, TS, NS, or SHOX deficiency confirmed by a genetic test;
17. Request is for a somatropin formulation;
18. Prescribed by or in consultation with a pediatric endocrinologist;
19. Age < 18 years;
20. If age > 10 years, open epiphysis on x-ray;
21. Member meets one of the following (a or b): a. SS: height is > 2 SD below the mean for age and sex (> 1.5 SD if TS) (SD, height, date, and age in months within the last 90 days are required); b. GF: one of the following (i, ii, or iii): i. Height deceleration across two growth chart percentiles representing > 1 SD below the mean for age and sex (SD and 2 heights, dates, and ages in months at least 6 months apart within the last year are required); ii. Growth velocity > 2 SD below the mean for age and sex over 1 year (SD and 2 heights, dates, and ages in months at least 1 year apart within the last year are required); iii. Growth velocity > 1.5 SD below the mean for age and sex sustained over 2 years (SD and 2 heights, dates, and ages in months at least 2 years apart within the last two years are required);
    
    7. The requested product is not prescribed concurrently with Increlex (mecasermin);

22. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
    a. Member must use Norditropin and Humatrope; b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope vial, unless contraindicated or clinically significant adverse effects are experienced;
    c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Norditropin, Humatrope, and Omnitrope

    9. Request meets one of the following (a, b, or c): a. PWS: Dose does not exceed 0.24 mg/kg per week;
       b. TS, NS: Dose does not exceed 0.5 mg/kg per week;
       c. SHOX deficiency: Dose does not exceed 0.35 mg/kg per week. Approval duration: 6 months Page 5 of 20

    CLINICAL POLICY
    Human Growth Hormone D. Chronic Kidney Disease with Growth Failure – Children (must meet all):

    1. Diagnosis of CKD;
23. Request is for a somatropin formulation;
24. Prescribed by or in consultation with a pediatric endocrinologist or nephrologist;
25. Age < 18 years;
26. If age > 10 years, open epiphysis on x-ray;
27. Member meets one of the following (a, b, c, or d): a. GFR < 60 mL/min per 1.73 m2 for ≥ 3 months; b. Dialysis dependent; c. Diagnosis of nephropathic cystinosis; d. History of kidney transplant ≥ 1 year ago;
28. Member meets one of the following (a or b): a. SS: height is > 2 SD below the mean for age and sex (SD, height, date, and age in months within the last 90 days are required); b. GF: one of the following (i, ii, or iii): i. Height deceleration across two growth chart percentiles representing > 1 SD below the mean for age and sex (SD and 2 heights, dates, and ages in months at least 6 months apart within the last year are required); ii. Growth velocity > 2 SD below the mean for age and sex over 1 year (SD and 2 heights, dates, and ages in months at least 1 year apart within the last year are required); iii. Growth velocity > 1.5 SD below the mean for age and sex sustained over 2 years (SD and 2 heights, dates, and ages in months at least 2 years apart within the last two years are required);
    
    8. The requested product is not prescribed concurrently with Increlex (mecasermin);
29. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
    a. Member must use Norditropin and Humatrope; b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope vial, unless contraindicated or clinically significant adverse effects are experienced;
    c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Norditropin, Humatrope, and Omnitrope 10. Dose does not exceed 0.35 mg/kg per week. Approval duration: 6 months E. Born Small for Gestational Age with Short Stature/Growth Failure - Children (must meet all):
30. Diagnosis of SGA:
31. Request is for a somatropin formulation;
32. Prescribed by or in consultation with a pediatric endocrinologist;
33. Age ≥ 2 years and < 18 years;
34. If age > 10 years, open epiphysis on x-ray;

35. Birth weight or length > 2 SD below the mean for gestational age (SD, birth weight or length, and gestational age are required);
    Page 6 of 20

    CLINICAL POLICY
    Human Growth Hormone

    7. Current height > 2 SD below the mean for age and sex measured within the last year at ≥ 2 years of age (SD, height, date, and age in months are required);
    8. The requested product is not prescribed concurrently with Increlex (mecasermin);
36. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
    a. Member must use Norditropin and Humatrope; b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope vial, unless contraindicated or clinically significant adverse effects are experienced;
    c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Norditropin, Humatrope, and Omnitrope 10. Dose does not exceed 0.48 mg/kg per week. Approval duration: 6 months F. Idiopathic Short Stature - Children (must meet all):
    1. Diagnosis of ISS;
37. Request is for a somatropin formulation;
38. Prescribed by or in consultation with a pediatric endocrinologist;
39. Age < 18 years;
40. If age > 10 years, confirmation of open epiphysis on x-ray;
41. Member meets both of the following (a and b): a. Height > 2.25 SD below the mean for age and sex (SD, height, date, and age in months within the last 90 days required); b. Not likely to attain adult height in the normal range (predicted height is < 63 inches for males and < 59 inches for females);
    7. All the following conditions have been ruled out (a, b, and c): a. Short stature related to GHD, genetic disease, CKD, SGA; b. Familial (genetic) short stature (i.e., height velocity and bone age, as determined by x-ray, are within the normal range and one or both parents are short); c. Constitutional delay of growth and puberty (i.e., the member’s growth rate is delayed compared to chronological age but appropriate for bone age as determined by x-ray);
    8. The requested product is not prescribed concurrently with Increlex (mecasermin);
42. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
    a. Member must use Norditropin and Humatrope; b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope vial, unless contraindicated or clinically significant adverse effects are experienced;
    c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Norditropin, Humatrope, and Omnitrope 10. Dose does not exceed 0.30 mg/kg per week. Approval duration: 6 months G. Growth Hormone Deficiency – Adults and Transition Patients (closed epiphyses) (must meet all):

43. Diagnosis of GHD; Page 7 of 20

    CLINICAL POLICY
    Human Growth Hormone

    2. Request is for a somatropin or somapacitan formulation;
44. Prescribed by or in consultation with an endocrinologist;
45. Age ≥ 18 years OR closed epiphysis on x-ray;
46. Member has NOT received somatropin therapy for ≥ 1 month prior to GH/IGF-I testing as outlined below;
    6. Member meets one of the following (a, b, or c): a. Two fasting a.m. GH stimulation tests with peak serum levels ≤ 5 µg/mL (accepted stimulants: Macrilen™ [macimorelin] or combination of 2 stimulants such as arginine + glucagon);
       b. Both of the following (i and ii):
       i. One fasting a.m. GH stimulation test with peak serum level ≤ 5 µg/ml (accepted stimulants: Macrilen [macimorelin] or combination of 2 stimulants such as arginine + glucagon);
       ii. One low IGF-I serum level;
       c. One low IGF-I serum level and one of the following (i, ii, or iii):
       Imaging shows hypothalamic-pituitary abnormality;
       i. ii. Deficiency of ≥ 3 pituitary hormones (i.e., ACTH, TSH, LH, FSH, prolactin); iii. GHD-specific mutation (e.g., POU1F1, PROP1, LHX3, LHX4, HESX1, OTX2, TBX19, SOX2, SOX3, GLI2, GHRHR, GH1);
    7. The requested product is not prescribed concurrently with Increlex (mecasermin);
47. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
    a. Member must use Norditropin and Humatrope; b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope vial, unless contraindicated or clinically significant adverse effects are experienced;
    c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Norditropin, Humatrope, and Omnitrope
    9. Dose does not exceed one of the following (a or b): a. For Sogroya: 8 mg once weekly; b. For somatropin agents: 0.4 mg/day (may adjust by up to 0.2 mg/day every 4 weeks to maintain normal IGF-1 serum levels; doses > 1.6 mg/day would be uncommon). Approval duration: 6 months H. Short Bowel Syndrome (must meet all):
    10. Diagnosis of SBS;
48. Request is for a somatropin formulation;
49. Prescribed by or in consultation with a gastroenterologist;
50. Age ≥ 18 years;
51. Patient is dependent upon and receiving intravenous nutrition;

52. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
    a. Member must use Norditropin and Humatrope; b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope* vial, unless contraindicated or clinically significant adverse effects are experienced;
    Page 8 of 20

    CLINICAL POLICY
    Human Growth Hormone c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; *Prior authorization may be required for Norditropin, Humatrope, and Omnitrope

    7. Dose does not exceed 8 mg per day. Approval duration: up to 4 weeks total I. HIV-Associated Wasting or Cachexia (must meet all):
    8. Diagnosis of HIV;
53. Request is for a somatropin formulation;
54. Prescribed by or in consultation with a physician specializing in HIV management;
55. Age ≥ 18 years;
56. Member meets one of the following (a, b, or c):
    a. Unintentional weight loss of ≥ 10% in the last 12 months occurring while on antiretroviral therapy; b. Weight < 90% of the lower limit of ideal body weight;
    c. Body mass index (BMI) ≤ 20 kg/m2;
    6. Failure of at least 2 pharmacologic therapies from two separate drug classes (Appendix B) unless contraindicated or clinically adverse effects are experienced;
    7. Member is currently on antiretroviral therapy;

57. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c): a. Member must use Norditropin and Humatrope; b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope vial, unless contraindicated or clinically significant adverse effects are experienced;
    c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Norditropin, Humatrope, and Omnitrope

    9. Dose does not exceed 6 mg per day. Approval duration: 6 months (up to 12 months total) J. Other diagnoses/indications (must meet 1 and 2):
    10. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
        a. Member must use Norditropin and Humatrope; b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope vial, unless contraindicated or clinically significant adverse effects are experienced;
        c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; PA may be required for Norditropin, Humatrope, and Omnitrope
    11. Member meets one of the following (a or b): a. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (i or ii): i. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial; or Page 9 of 20

    CLINICAL POLICY
    Human Growth Hormone ii. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial; or b. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 2a above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial.
    II. Continued Therapy A. All Pediatric Indications (open epiphyses) (must meet all):

    1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
58. Age < 18 years OR open epiphysis on x-ray;
59. Member meets one of the following (a or b): a. For diagnosis of neonatal hypoglycemia, when member has received somatropin therapy for ≥ 2 years, member’s height has increased ≥ 2 cm in the last year as documented by 2 height measurements taken no more than 1 year apart (dates and height measurements required);
    b. For all other pediatric diagnoses, member’s height has increased ≥ 2 cm in the last year as documented by 2 height measurements taken no more than 1 year apart (dates and height measurements required);
    
    4. If request is for a dose increase, request meets one of the following (a, b, c, d, or e): a. GHD, one of the following (i, ii, or iii): i. For Ngenla (without neonatal hypoglycemia): New dose does not exceed 0.66 mg/kg per week; ii. For Sogroya (without neonatal hypoglycemia): New dose does not exceed 0.16 mg/kg per week; iii. For somatropin agents (with or without neonatal hypoglycemia): New dose does not exceed 0.30 mg/kg per week; b. PWS: New dose does not exceed 0.24 mg/kg per week;
       c. TS, NS: New dose does not exceed 0.5 mg/kg per week;
       d. SHOX deficiency, CKD: New dose does not exceed 0.35 mg/kg per week; e. Born SGA: New dose does not exceed 0.48 mg/kg per week. Approval duration: 12 months B. Growth Hormone Deficiency - Adults and Transition Patients (closed epiphyses) (must meet all):

60. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 10 of 20

    CLINICAL POLICY
    Human Growth Hormone b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

61. Member is responding positively to therapy;
62. For IGF-1 test results and dosing (test conducted within the last 90 days), one of the following (a, b, or c): a. Low IGF-1 serum level (i or ii): i. For Sogroya: 8 mg once weekly; ii. For somatropin formulations: If request is for a dose increase, new dose does not exceed an incremental increase of more than 0.2 mg/day and a total dose of 1.6 mg/day; b. Normal IGF-1 serum level: Requested dose is for the same or lower dose; c. Elevated IGF-1 serum level: Requested dose has been titrated downward. Approval duration: 12 months C. Short Bowel Syndrome - Adults (must meet all):
63. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
64. Member is responding positively to therapy;
65. Member has not received the requested product for ≥ 4 weeks;
66. If request is for a dose increase, new dose does not exceed 8 mg per day. Approval duration: up to 4 weeks total D. HIV-Associated Wasting/Cachexia - Adults (must meet all):
    
    1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
67. Member is responding positively to therapy;
68. Member has not received ≥ 12 months of therapy;

69. If request is for a dose increase, new dose does not exceed 6 mg per day. Approval duration: 12 months (up to 12 months total) E. Other diagnoses/indications (must meet 1 and 2):

    1. If request is NOT for Norditropin or Humatrope, one of the following (a, b, or c):
       a. Member must use Norditropin and Humatrope; b. If both Norditropin and Humatrope are not available (e.g., due to drug shortages) member must use Omnitrope* vial, unless contraindicated or clinically significant adverse effects are experienced;
       Page 11 of 20

    CLINICAL POLICY
    Human Growth Hormone c. Norditropin, Humatrope, and Omnitrope are all contraindicated or clinically significant adverse effects are experienced; *PA may be required for Norditropin, Humatrope, and Omnitrope

    2. Member meets one of the following (a or b): a. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (i or ii): i. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial; or ii. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial; or b. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 2a above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial.
       III. Diagnoses/Indications for which coverage is NOT authorized:
       A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – HIM.PA.154 for health insurance marketplace, or evidence of coverage documents; B. Constitutional delay of growth and puberty (i.e., constitutional growth delay; the member’s growth rate is delayed compared to chronological age but appropriate for bone age as determined by x-ray); C. Familial (genetic) short stature (i.e., height velocity and bone age, as determined by x- ray, are within the normal range and one or both parents are short); D. Adult short stature or altered body habitus associated with antiviral therapy (other than HIV-associated wasting or cachexia); E. Obesity treatment or enhancement of body mass/strength for non-medical reasons (e.g., athletic gains). IV. Appendices/General Information Appendix A: Abbreviation AO: adult-onset CKD: chronic kidney disease CO: childhood-onset FDA: Food and Drug Administration
       GF: growth failure GFR: glomerular filtration rate GH: growth hormone GHD: growth hormone deficiency hGH: human growth hormone HIV: human immunodeficiency virus IGF-1: insulin-like growth factor-1 IGFBP-3: insulin-like growth factor binding protein-3
       ISS: idiopathic short stature NS: Noonan syndrome PWS: Prader-Willi syndrome rhGH: recombinant human growth hormone
       SBS: short bowel syndrome SD: standard deviation
       SGA: small for gestational age SHOX: short stature homeobox-containing gene SS: short stature Page 12 of 20

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    Human Growth Hormone TS: Turner syndrome Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Dosing Regimen Dose Limit/Maximum Dose Appetite Stimulants megestrol (Megace, Syndros) dronabinol (Marinol) Testosterone Replacement Products testosterone enanthate or cypionate (various brands) Androderm (testosterone transdermal patch) testosterone transdermal gel (Androgel, Testim) 400 - 800 mg PO daily (10 – 20 ml/day) 2.5 mg PO BID 50 - 400 mg IM Q2 – 4 wks 2.5 – 7.5 mg patch applied topically QD 5 - 10 gm gel (delivers 50 – 100 mg testosterone) applied topically QD Anabolic Steroids oxandrolone (Oxandrin)
    Nausea/Vomiting Treatments chlorpormazine 2.5 – 20 mg PO /day 800 mg/day 20 mg/day 400 mg Q 2 wks 7.5 mg/day 10 gm/day gel (100 mg/day testosterone)
    20 mg/day perphenazine 2,000 mg/day prochlorperazine promethazine 10 to 25 mg PO q4 to 6 hours prn 8 to 16 mg/day PO in divided doses 5 to 10 mg PO TID or QID 12.5 to 25 mg PO q4 to 6 hours prn trimethobenzamide 300 mg PO TID or QID prn Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Preferred status may be formulary specific. 40 mg/day 50 mg/dose; 100 mg/day 1,200 mg/day 64 mg/day Appendix C: Contraindications/Boxed Warnings • Somatropin contraindications: o Acute critical illness o Children with PWS who are severely obese or have severe respiratory impairment (reports of sudden death) o Active malignancy o Product hypersensitivity o Active proliferative or severe non-proliferative diabetic retinopathy o Children with closed epiphyses • Sogroya and Ngenla contraindications: o Acute critical illness Page 13 of 20

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    Human Growth Hormone o Active malignancy o Hypersensitivity to somapacitan-beco/somatrogon-ghla or excipients o Active proliferative or severe non-proliferative diabetic retinopathy o Pediatric patients with closed epiphyses o Pediatric patients with PWS who are severely obese, have history of upper airway obstruction or sleep apnea or have severe respiratory impairment due to risk of sudden death • Boxed warning(s): none reported Appendix D: Short Stature and Growth Failure • For SS, the policy follows the World Health Organization (WHO) definition of > 2 SD below the mean for age and sex.1 • For GF, the policy follows: o o Haymond et al (2013) and Rogol et al (2014) for height deceleration across two major percentiles representing a change of > 1 SD corrected for age and sex2,3 and the Growth Hormone Research Society (2000) for height velocity in the absence of SS that would prompt further investigation, namely, a height velocity > 2 SD below the mean over 1 year or > 1.5 SD below the mean sustained over 2 years for age and sex.4 • The Centers for Disease Control and Prevention (CDC) recommend WHO growth charts for infants and children age 0 to < 2 years and CDC growth charts for children age 2 years to < 20 years in the U.S.5
    o Based on CDC recommended growth chart data, SD approximations of major height percentiles falling below the mean are listed below:  2nd percentile: 2 SD below the mean  5th percentile: 1.5 SD below the mean  15th percentile: 1 SD below the mean  30th percentile: 0.5 SD below the mean  50th percentile: 0 SD mean o CDC recommended growth charts, data tables, and related information that may be helpful in assessing length, height and growth are available at the following link: https://www.cdc.gov/growthcharts/index.htm.
    ____

70. WHO Child Growth Standards: Length/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index-for-Age: Methods and Development. Geneva, Switzerland: World Health Organization; 2006. As cited in CDC. Division of Nutrition, Physical Activity, and Obesity. Growth Chart Training: Using the WHO Growth Charts. Page last reviewed January 13, 2022. Available at https://www.cdc.gov/nccdphp/dnpao/growthcharts/who/using/assessing_growth.htm. Accessed November 27. 2023.
71. Haymond M, Kappelgaard AM, Czernichow P, et al. Early recognition of growth abnormalities permitting early intervention. Acta Pædiatrica ISSN 0803-5253. April 2013. DOI:10.1111/apa.12266.
72. Rogol AD, Hayden GF. Etiologies ad early diagnosis of short stature and growth failure in children and adolescents. J Pediatr. 2014 May;164(5 Suppl):S1-14.e6. doi: 10.1016/j.jpeds.2014.02.027.
73. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. JCEM. 2000; 85(11): 3990-3993.

74. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC growth charts: United States. http://www.cdc.gov/growthcharts/. Accessed November 27. 2023.
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    Human Growth Hormone V. Dosage and Administration Maximum Dose 0.24 mg/kg/week 0.48 mg/kg/week TS SGA PWS See dosing regimens
    Indication Dosing Regimen G, O: to 0.48 mg/kg/week H, N, Z: to 0.47 mg/kg/week G, O: 0.16 to 0.24 mg/kg/week H, Z: 0.18 to 0.30 mg/kg/week N: 0.17 to 0.24 mg/kg/week Nu: to 0.30 mg/kg/week S: 0.18 mg/kg/week G, N, O: 0.24 mg/kg/week Drug Name
    Pediatric Indications (Subcutaneous administration; weekly doses should be divided [except Sogroya and Ngenla]) GHD Genotropin, Humatrope, Norditropin, Nutropin, Omnitrope, Saizen, Zomacton
    Genotropin, Norditropin, Omnitrope
    Genotropin, Humatrope, Norditropin, Omnitrope, Zomacton
    Genotropin, Humatrope, Norditropin, Nutropin, Omnitrope, Zomacton
    Genotropin, Humatrope, Norditropin, Nutropin, Omnitrope, Zomacton
    Humatrope, Zomacton SHOX Norditropin
    Nutropin
    Sogroya Ngenla Adult Indications (Subcutaneous administration) Genotropin, Humatrope, Norditropin, Nutropin, Omnitrope, Saizen, Zomacton
    G, O: 0.33 mg/kg/week H, Nu, Z: to 0.375 mg/kg/week N: to 0.47 mg/kg/week G, O, No: to 0.47 mg/kg/week H, Z: to 0.37 mg/kg/week Nu: to 0.30 mg/kg/week H, Z: 0.35 mg/kg/week 0.46 mg/kg/week
    0.35 mg/kg/week 0.16 mg/kg once weekly 0.66 mg/kg once weekly NS CKD GHD GHD See dosing regimens See dosing regimen See dosing regimens GHD ISS 0.4 mg/day - may adjust by increments up to 0.2 mg/day every 6 weeks to maintain normal IGF-1 serum levels. ____ Dosing regimen from Endocrine Society guidelines (Fleseriu, et al., 2016).
    0.35 mg/kg/week 0.46 mg/kg/week 0.35 mg/kg/week 0.16 mg/kg/week 0.66 mg/kg/week Adult GHD dosing should be substantially lower than that prescribed for children. Adult doses beyond 1.6 mg/day would be uncommon.
    0.1 mg/kg QOD or QD to 6 mg QD 6 mg/day up to 24 weeks Serostim HIV- associated wasting Page 15 of 20

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    Human Growth Hormone Drug Name
    Sogroya Zorbtive SBS VI. Product Availability Indication Dosing Regimen GHD 1.5 mg once weekly – increase by increments of 0.5-1.5 mg every 2-4 weeks based on clinical response and serum IGF-1 concentrations 0.1 mg/kg QD to 8 mg QD Maximum Dose 8 mg/week 8 mg/day up to 4 weeks Drug Genotropin lyophilized powder MD dual-chamber syringe: 5 mg, 12 mg Genotropin Miniquick Availability* Humatrope Ngenla Norditropin Flexpro Nutropin AQ NuSpin Omnitrope Saizen Serostim Sogroya Zomacton Zorbtive SD: single-dose, MD: multidose SD pen cartridge: 0.2 mg, 0.4 mg, 0.6 mg, 0.8 mg, 1.0 mg, 1.2 mg, 1.4 mg, 1.6 mg. 1.8 mg, and 2.0 mg MD pen cartridge: 6 mg, 12 mg, 24 mg MD vial: 5mg MD pen: 24 mg/1.2 mL, 60 mg/1.2 mL MD pen: 5 mg/1.5 mL, 10 mg/1.5 mL, 15 mg/1.5 mL, 30 mg/3 mL MD: 5 mg/2 mL, 10 mg/2 mL, 20 mg/2 mL MD pen cartridge: 5 mg/1.5 mL, 10 mg/1.5 mL MD vial: 5.8 mg MD pen cartridge: 8.8 mg MD vial: 5 mg, 8.8 mg
    MD vial: 4 mg SD vial: 5 mg, 6 mg MD pen: 5 mg/1.5 mL, 10 mg/1.5 mL, 15 mg/1.5 mL MD vial: 5 mg, 10 mg MD vial: 8.8 mg VII.