Skytrofa (Lonapegsomatropin-Tcgd)

SKYTROFA (lonapegsomatropin-tcgd) is a human growth hormone indicated for the:

• Treatment of pediatric patients 1 year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone (GH).
• Replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD).

• SKYTROFA should be administered subcutaneously once weekly into the abdomen, buttock, or thigh with regular rotation of the injection sites (
  2.7 Preparation and Administration

  • The SKYTROFA cartridge has been designed for use only with the SKYTROFA Auto-Injector.
  • If refrigerated, the SKYTROFA cartridge must be kept at room temperature for 15 minutes before use.
  • The SKYTROFA Auto-Injector provides a fully automated reconstitution of the lyophilized drug product which is followed by a manual mixing step controlled by the device. When the injection needle is inserted into the skin, the device automatically delivers the drug product. The built-in electronics and software assist the user during the entire preparation and injection sequence and provide confirmation that the full dose has been delivered.
  • The mixed solution should be clear and colorless to opalescent. The solution may contain air bubbles and this is acceptable. DO NOT inject if the solution is cloudy or contains particulate matter.
  • Use SKYTROFA cartridges within 4 hours after reconstitution. Discard reconstituted SKYTROFA cartridges after 4 hours when stored at room temperature up to 86°F (30°C).
  • Inject SKYTROFA subcutaneously into the abdomen, buttock, or thigh. Rotate injection sites between and within regions to reduce the risk of lipoatrophy
    [see Warnings and Precautions (5.12)]
    .
  • Refer to the Instructions for Use for complete administration instructions with illustrations. The instructions can also be found on www.Skytrofa.com/IFU.
  • Patients and/or caregivers who will administer SKYTROFA should receive appropriate training and instruction on the proper use of SKYTROFA from their healthcare provider.
  ).
• Pediatric Patients: Recommended dose is 0.24 mg/kg body weight once weekly (
  2.2 Recommended Dosage for Pediatric Patients

  • The recommended dose of SKYTROFA for treatment-naïve patients and patients switching from another growth hormone product is 0.24 mg/kg body weight, given once weekly.
  • Individualize and titrate the dosage of SKYTROFA based on response.
  • When changing from daily somatropin therapy to once-weekly SKYTROFA, wait at least 8 hours between the final dose of daily somatropin and the first dose of SKYTROFA.
  • When changing from another once-weekly growth hormone therapy to once-weekly SKYTROFA, wait at least 7 days between the final dose of the previous growth hormone therapy and the first dose of SKYTROFA.
  • Assess compliance and evaluate other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age and antibodies to recombinant human growth hormone if patients experience failure to increase height velocity, particularly during the first year of treatment.
  • Patients who were treated with SKYTROFA for GH deficiency in childhood and whose epiphyses are closed should be reevaluated before continuing SKYTROFA.
  ).
• Adults: Recommended starting dose is based on age and concomitant use of oral estrogen. Titrate monthly until the desired clinical response and/or weekly average IGF-1 concentration are achieved (
  2.3 Recommended Dosage for Adults

  • The recommended starting dose of SKYTROFA in adults with GHD is based on age and concomitant use of oral estrogen

    [see Dosage Forms and Strengths (3)]

    . For treatment-naïve patients or for patients switching from another growth hormone product, start SKYTROFA as described below:
    • 1.4 mg once weekly for adults 30 to 60 years old, with no oral estrogen intake
    • 2.1 mg once weekly for adults under 30 years old, or adults of any age intaking oral estrogen
    • 0.7 mg once weekly for adults over 60 years old, with no oral estrogen intake
  • When changing from daily somatropin therapy to once-weekly SKYTROFA, wait at least 8 hours between the final dose of daily somatropin and the first dose of SKYTROFA.
  • When changing from another once-weekly growth hormone therapy to once-weekly SKYTROFA, wait at least 7 days between the final dose of the previous growth hormone therapy and the first dose of SKYTROFA.
  • Increase the dose monthly to a higher strength cartridge based on the clinical response and/or IGF-1 concentration. Draw IGF-1 serum sample 4 to 5 days after the prior dose.
  • Decrease the dose to a lower strength cartridge as needed based on adverse reactions or a weekly average IGF-1 concentration above the age- and sex-specific normal range.
  • The maximum recommended dose is 6.3 mg once weekly.
  ).
• See Full Prescribing Information for instructions on preparation and administration of drug (
  2.5 Administration Instructions for Pediatric Patients

  SKYTROFA is available in 9 cartridges (dosage strengths in somatropin equivalents) for pediatric patients.

  Selection of the appropriate cartridge (mg) is based on the prescribed dose (mg/kg) and the patient's body weight (kg)

  [see Dosage Forms and Strengths (3)]

  .

  • If prescribing a dose of 0.24 mg/kg/week and the patient's weight is 11.5 to 100 kg, follow the recommended dosing in Table 1.
  • If prescribing a dose other than 0.24 mg/kg/week, calculate the total weekly dose (in mg) and select the appropriate cartridge as follows:
    • Total weekly dose (mg) = prescribed weekly dose (mg/kg) × patient's body weight (kg).
    • Round the total weekly dose (mg) to the closest cartridge dose while also considering treatment goals and clinical response.

  Table 1: Recommended Dosing for Pediatric Patients Prescribed Doses of 0.24 mg/kg/week

  Weight (kg)	Dose (mg)
  11.5 – 13.9	3
  14 – 16.4	3.6
  16.5 – 19.9	4.3
  20 – 23.9	5.2
  24 – 28.9	6.3
  29 – 34.9	7.6
  35 – 41.9	9.1
  42 – 50.9	11
  51 – 60.4	13.3
  60.5 – 69.9	15.2 (using two cartridges of 7.6 mg each)
  70 – 84.9	18.2 (using two cartridges of 9.1 mg each)
  85 – 100	22 (using two cartridges of 11 mg each)
  ,
  2.6 Administration Instructions for Adults

  SKYTROFA is available in 14 cartridges (dosage strengths in somatropin equivalents) for adults.

  Selection of the appropriate cartridge (mg) is based on the prescribed dose (mg/week)

  [see Dosage Forms and Strengths (3)]

  .
  ,
  2.7 Preparation and Administration

  • The SKYTROFA cartridge has been designed for use only with the SKYTROFA Auto-Injector.
  • If refrigerated, the SKYTROFA cartridge must be kept at room temperature for 15 minutes before use.
  • The SKYTROFA Auto-Injector provides a fully automated reconstitution of the lyophilized drug product which is followed by a manual mixing step controlled by the device. When the injection needle is inserted into the skin, the device automatically delivers the drug product. The built-in electronics and software assist the user during the entire preparation and injection sequence and provide confirmation that the full dose has been delivered.
  • The mixed solution should be clear and colorless to opalescent. The solution may contain air bubbles and this is acceptable. DO NOT inject if the solution is cloudy or contains particulate matter.
  • Use SKYTROFA cartridges within 4 hours after reconstitution. Discard reconstituted SKYTROFA cartridges after 4 hours when stored at room temperature up to 86°F (30°C).
  • Inject SKYTROFA subcutaneously into the abdomen, buttock, or thigh. Rotate injection sites between and within regions to reduce the risk of lipoatrophy
    [see Warnings and Precautions (5.12)]
    .
  • Refer to the Instructions for Use for complete administration instructions with illustrations. The instructions can also be found on www.Skytrofa.com/IFU.
  • Patients and/or caregivers who will administer SKYTROFA should receive appropriate training and instruction on the proper use of SKYTROFA from their healthcare provider.
  ).

SKYTROFA is a white to off-white lyophilized powder available in a single-dose, dual-chamber, prefilled cartridge containing lonapegsomatropin-tcgd in one chamber and diluent, Water for Injection, in the other chamber and is available in the following strengths:

For injection: 0.7 mg, 1.4 mg, 1.8 mg, 2.1 mg, 2.5 mg, 3 mg, 3.6 mg, 4.3 mg, 5.2 mg, 6.3 mg, 7.6 mg, 9.1 mg, 11 mg, and 13.3 mg.

There are no available data on lonapegsomatropin-tcgd use in pregnant patients to evaluate a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Available published data over several decades for somatropin, the active component of lonapegsomatropin-tcgd, have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of embryo-fetal or neonatal harm when pregnant rats were administered subcutaneous lonapegsomatropin-tcgd at doses up to 13-fold the clinical pediatric dose of 0.24 mg/kg/week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg hGH/week

The estimated background risk of birth defects and miscarriages for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.