SKYTROFA- lonapegsomatropin-tcgd_injection, powder, lyophilized, for solution

SKYTROFA is a pegylated human growth hormone (somatropin) for once-weekly subcutaneous injection [see Clinical Pharmacology (12. 3) Somatropin binds to the growth hormone (GH) receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Somatropin has direct tissue and metabolic effects, and indirect effects mediated by insulin-like growth factor-1 (IGF-1), including stimulation of chondrocyte differentiation and proliferation, stimulation of hepatic glucose output, protein synthesis and lipolysis. Somatropin stimulates skeletal growth in pediatric patients with growth hormone deficiency (GHD) as a result of effects on the growth plates (epiphyses) of long bones. Somatropin released from SKYTROFA produces a linear IGF-1 dose response. In pediatric patients with GHD, with a dose change of 0. 02 mg/kg/week on average resulting in a mean change in weekly average IGF-1 standard deviation score (SDS) of 0. In adults with GHD, a dose change of 1 mg/week results in a mean change in weekly average IGF-1 SDS of 0. 7 (range, 0. At steady state, IGF-1 levels peak approximately 2 days post-dose, with the weekly average IGF-1 occurring approximately 4. 5 days post-dose. IGF-1 levels are in the normal range for GHD patients for the majority of the week, similar to daily somatropin. Absorption Following subcutaneous dose administration, SKYTROFA releases fully active somatropin via autocleavage of the TransCon linker that follows first-order kinetics. In pediatric patients with GHD, following subcutaneous dose administration of 0. 24 mg/kg/week SKYTROFA, the observed mean (CV%) steady-state peak serum concentration (C max max max max max max In adult patients with GHD, following subcutaneous administration of 6. 3 mg/week SKYTROFA, the estimated median steady-state C max max max max max max No significant accumulation of lonapegsomatropin-tcgd and somatropin following repeat dose administration was observed. Distribution In pediatric patients with GHD, the mean (CV%) steady-state apparent volume of distribution of lonapegsomatropin-tcgd after subcutaneous administration of 0. 24 mg/kg/week SKYTROFA was 0. 13 (109) L/kg. In adult patients with GHD, the median steady-state apparent volume of distribution of lonapegsomatropin-tcgd after subcutaneous administration of 6. 3 mg/week SKYTROFA was 0. A similar distribution pattern as observed for daily somatropin is expected once somatropin is released from lonapegsomatropin-tcgd. Elimination Metabolism The metabolism of somatropin involves protein catabolism in both the liver and kidneys. The methoxypolyethylene glycol carrier is cleared by the kidneys. Excretion In pediatric patients with GHD, the mean (CV%) lonapegsomatropin-tcgd apparent clearance at steady state was 3. 2 (67) mL/h/kg following subcutaneous administration of 0. 24 mg/kg/week SKYTROFA with a mean (+/-SD) observed half-life of 30. The apparent half-life of somatropin released from lonapegsomatropin-tcgd was approximately 25 hours. Specific Populations Based on a population pharmacokinetic analysis, age (3. 7 years for pediatric patients and 23 to 75 years for adult patients), sex, race, and body weight do not have clinically meaningful effects on pharmacokinetics. Male and Female Patients em dash No sex-specific pharmacokinetic studies have been performed with SKYTROFA. The available literature indicates that the pharmacokinetics of somatropin are similar in men and women. Patients with Renal or Hepatic Impairment em dash No specific studies have been performed with SKYTROFA. The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of SKYTROFA or other growth hormone products. Anti-lonapegsomatropin-tcgd antibodies were evaluated in samples collected every 3 months in phase 3 trials in pediatric patients with GHD receiving SKYTROFA. Mean duration of exposure to SKYTROFA was 70. Of the 304 patients with post-baseline assessments, 19 (6. 3%) showed detectable binding antibodies to lonapegsomatropin-tcgd. No apparent correlation of anti-lonapegsomatropin-tcgd antibodies to adverse events or loss of efficacy was observed. No neutralizing antibodies to SKYTROFA were detected. Of the 247 adult patients with GHD, treated with SKYTROFA and with post-baseline assessments, antibodies against lonapegsomatropin-tcgd were detected in 14 patients (5. 7%, mean duration of exposure was 47. There was no identified clinically significant effect of anti-lonapegsomatropin-tcgd antibodies on the safety and efficacy of SKYTROFA.

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 is a human growth hormone indicated for: Pediatric Patients: 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) ( 1 Adults: Replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD) ( 1.

SKYTROFA should be administered subcutaneously once weekly into the abdomen, buttock, or thigh with regular rotation of the injection sites ( 2. 7 Pediatric Patients: Recommended dose is 0. 24 mg/kg body weight once weekly ( 2. 2 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 See Full Prescribing Information for instructions on preparation and administration of drug ( 2. 7 For subcutaneous injection, once weekly. Therapy with SKYTROFA should be supervised by a healthcare provider who is experienced in the diagnosis and management of patients with growth hormone deficiency (GHD). Perform fundoscopic examination before initiating treatment with SKYTROFA to exclude preexisting papilledema. If papilledema is identified, evaluate the etiology and treat the underlying cause before initiating treatment with SKYTROFA [see Warnings and Precautions (5. 5) 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. 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) 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. 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. Administer a missed dose as soon as possible and not more than 2 days after the missed dose. To avoid missed doses, SKYTROFA can be taken 2 days before or 2 days after the scheduled dosing day. Resume once-weekly dosing for the next dose at the previously scheduled dosing day. If more than 2 days have passed from the scheduled day, skip the dose and administer the next dose on the regularly scheduled day. At least 5 days should elapse between doses. 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 en dash 13. 9 3 14 en dash 16. 5 en dash 19. 3 20 en dash 23. 2 24 en dash 28. 3 29 en dash 34. 6 35 en dash 41. 1 42 en dash 50. 9 11 51 en dash 60. 5 en dash 69. 2 (using two cartridges of 7. 6 mg each) 70 en dash 84. 2 (using two cartridges of 9. 1 mg each) 85 en dash 100 22 (using two cartridges of 11 mg each) 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) 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. Patients and/or caregivers who will administer SKYTROFA should receive appropriate training and instruction on the proper use of SKYTROFA from their healthcare provider.

The following important adverse reactions are described elsewhere in the labeling: Increased mortality in patients with acute critical illness [see Warnings and Precautions (5. 1) Severe hypersensitivity [see Warnings and Precautions (5. 2) Increased risk of neoplasms [see Warnings and Precautions (5. 3) Glucose intolerance and diabetes mellitus [see Warnings and Precautions (5. 4) Intracranial hypertension [see Warnings and Precautions (5. 5) Fluid retention [see Warnings and Precautions (5. 6) Hypoadrenalism [see Warnings and Precautions (5. 7) Hypothyroidism [see Warnings and Precautions (5. 8) Slipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions (5. 9) Progression of preexisting scoliosis in pediatric patients [see Warnings and Precautions (5. 10) Pancreatitis [see Warnings and Precautions (5. 11) Lipoatrophy [see Warnings and Precautions (5. 12) Sudden death in pediatric patients with Prader-Willi syndrome [see Warnings and Precautions (5. 13) Pediatric Patients: Most common adverse reactions (>= 5%): viral infection, pyrexia, cough, nausea and vomiting, hemorrhage, diarrhea, abdominal pain, and arthralgia and arthritis ( 6. 1 Adults: Most common adverse reaction (>= 5%): edema peripheral ( 6. 1 To report SUSPECTED ADVERSE REACTIONS, contact Ascendis Pharma Endocrinology, Inc. , at 1-844-442-7236 or FDA at 1-800-FDA-1088 or www. gov/medwatch. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. Pediatric Patients with Growth Hormone Deficiency SKYTROFA was studied in a 52-week, open-label, active-controlled trial in 161 treatment-naïve, prepubertal pediatric patients with growth hormone deficiency (GHD) [see Clinical Studies (14. 1) Table 2 shows common adverse reactions that occurred in >= 5% of patients treated with SKYTROFA in this trial. Table 2: Adverse Reactions Occurring in >= 5% SKYTROFA-Treated Pediatric Patients and More Frequently Than in Daily Somatropin-Treated Pediatric Patients (52 Weeks of Treatment) Adverse reactions Daily Somatropin SKYTROFA Adverse reactions that are medically related were grouped to a single preferred term. Infection, viral 6 (11%) 16 (15%) Pyrexia 5 (9%) 16 (15%) Cough 4 (7%) 11 (11%) Nausea and vomiting 4 (7%) 11 (11%) Hemorrhage Hemorrhage in the SKYTROFA treatment group included epistaxis (3), contusion (2), petechiae (1) and eye hemorrhage (1). 1 (2%) 7 (7%) Diarrhea 3 (5%) 6 (6%) Abdominal pain 2 (4%) 6 (6%) Arthralgia and arthritis Arthralgia and arthritis in the SKYTROFA treatment group included arthralgia (5) and reactive arthritis (1). 1 (2%) 6 (6%) Laboratory Tests More SKYTROFA-treated patients shifted from normal baseline levels to elevated phosphate and alkaline phosphatase levels at the end of the trial compared to the daily somatropin group (44. 4%, respectively); these laboratory changes occurred intermittently [see Warnings and Precautions (5. 14) Adults with Growth Hormone Deficiency SKYTROFA was studied in a 38-week parallel-arm, placebo-controlled (double-blind) and active-controlled (open label) trial in 259 adults with growth hormone deficiency (GHD) [see Clinical Studies (14. 2) The mean (range) age at enrollment was 43 (23 to 81) years old, with 119 (46%) females (55 on oral estrogen) and 140 (54%) males. One subject was American Indian or Alaska Native, one was Black or African American, 28 were Asian, and 218 were Caucasian. Table 3 shows adverse reactions that occurred in >= 5% of adults treated with SKYTROFA and more frequently than in placebo-treated adults in this trial. Table 3: Adverse Reactions Occurring in >= 5% of SKYTROFA-Treated Adults and More Frequently Than in Placebo-treated Adults (38 Weeks of Treatment) Adverse reactions Placebo SKYTROFA Adverse reactions that are medically related were grouped to a single preferred term. Edema Edema in the SKYTROFA treatment group included edema peripheral (6) and peripheral swelling (1). 1 (1%) 7 (8%) Central (secondary) hypothyroidism Central (secondary) hypothyroidism in the SKYTROFA treatment group included thyroxine free decreased (3), central hypothyroidism (2), thyroxine decreased (1), blood thyroid stimulating hormone decreased (1), tri-iodothyronine free decreased (1). Preexisting central hypothyroidism in 5 of 6 SKYTROFA-treated patients. 1 (1%) 6 (7%) Laboratory Tests More SKYTROFA-treated patients shifted from normal or low baseline levels to elevated alkaline phosphatase levels at the end of the trial compared to the placebo group (14% vs. 6%); these laboratory changes were noted with increased frequency as the trial progressed [see Warnings and Precautions (5. 14) The following adverse reactions have been identified during post approval use of somatropin products or SKYTROFA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Severe systemic hypersensitivity reactions, including anaphylactic reactions and angioedema Musculoskeletal and connective tissue disorders en dash osteonecrosis in pediatric patients.

SKYTROFA is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see Warnings and Precautions (5. 1) Hypersensitivity to somatropin or any of the excipients in SKYTROFA. Severe systemic hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported [see Warnings and Precautions (5. 2) Pediatric patients with closed epiphyses. Active malignancy due to the risk of malignancy progression [see Warnings and Precautions (5. 3) Active proliferative or severe non-proliferative diabetic retinopathy because treatment with somatropin may worsen this condition. Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea or have severe respiratory impairment due to the risk of sudden death [see Warnings and Precautions (5. 13) Acute critical illness ( 4 Hypersensitivity to somatropin or any of the excipients in SKYTROFA ( 4 Children with closed epiphyses ( 4 Active malignancy ( 4 Active proliferative or severe non-proliferative diabetic retinopathy ( 4 Children with Prader-Willi syndrome who are severely obese or have severe respiratory impairment due to risk of sudden death ( 4.

Risk Summary 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 (see Data 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. 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. Data Animal Data No embryonic or fetal development toxicities occurred in rats administered subcutaneous lonapegsomatropin-tcgd at doses up to 13-fold the clinical pediatric dose of 0. 3 mg hGH/week. In a peri- and post-natal developmental study in rats, there were no adverse effects on the pregnant/lactating female or on development of the conceptus and the offspring following exposure of the female from implantation through weaning to doses of a structurally related pegylated somatropin prodrug up to 13-fold the clinical pediatric dose of 0. Risk Summary There are no data on the presence of lonapegsomatropin-tcgd in human milk, effects on the breastfed infant, or effects on milk production. High molecular weight therapeutic proteins, including lonapegsomatropin-tcgd, are expected to have low passage into human milk and limited systemic exposure in the breastfed infant. Additionally, published data indicate that exogenous somatropin does not increase normal human milk concentrations of growth hormone. No adverse effects on the breastfed infant have been reported with somatropin. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SKYTROFA and any potential adverse effects on the breastfed infant from SKYTROFA or from the underlying maternal condition. Safety and effectiveness of SKYTROFA have been established in pediatric patients 1 year and older and who weigh at least 11. Pediatric use was established in a controlled study of 161 treatment-naïve pediatric patients ages 3 to 13 years and by supportive data in pediatric patients 1 year and older [see Adverse Reactions (6) Clinical Studies (14) The safety and effectiveness of SKYTROFA in children less than 1 year of age have not been established. Use of somatropin in pediatric patients with Prader-Willi syndrome has been associated with reports of sudden death. SKYTROFA is not indicated for the treatment of pediatric patients with growth failure due to genetically confirmed Prader-Willi syndrome [see Warnings and Precautions (5. 13) Of the 249 patients who received SKYTROFA in clinical studies, 24 (10%) patients were 65 years of age and older, and 4 (2%) patients were 75 years of age and older. Geriatric patients may be at an increased risk for adverse reactions. Initiate SKYTROFA at 0. 7 mg once weekly in patients 60 years of age and older, not on estrogen therapy [see Dosage and Administration (2.

Table 4 includes a list of drugs with clinically important drug interactions when administered concomitantly with SKYTROFA and instructions for preventing or managing them. Table 4: Clinically Important Drug Interactions with SKYTROFA Replacement Glucocorticoid Treatment Clinical Impact: Microsomal enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. Somatropin inhibits 11betaHSD-1. Consequently, individuals with untreated growth hormone deficiency (GHD) have relative increases in 11betaHSD-1 and serum cortisol. Initiation of SKYTROFA may result in inhibition of 11betaHSD-1 and reduced serum cortisol concentrations. Intervention: Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SKYTROFA [see Warnings and Precautions (5. 7) Examples Cortisone acetate and prednisone may be affected more than others because conversion of these drugs to their biologically active metabolites is dependent on the activity of 11betaHSD-1. Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment Clinical Impact: Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may attenuate the growth-promoting effects of SKYTROFA in pediatric patients. Intervention: Carefully adjust glucocorticoid replacement dosing in pediatric patients receiving glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth. Cytochrome P450-Metabolized Drugs Clinical Impact: Limited published data indicate that somatropin treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. SKYTROFA may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes. Intervention: Careful monitoring is advisable when SKYTROFA is administered in combination with drugs metabolized by CYP450 liver enzymes. Oral Estrogen Clinical Impact: Oral estrogens may reduce the serum insulin-like growth factor-1 (IGF-1) response to SKYTROFA. Intervention: Patients receiving oral estrogen replacement may require higher SKYTROFA dosages. Insulin and/or Other Antihyperglycemic Agents Clinical Impact: Treatment with SKYTROFA may decrease insulin sensitivity, particularly at higher doses. Intervention: Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents [see Warnings and Precautions (5. 4) Replacement Glucocorticoid Treatment: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SKYTROFA ( 7 Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment: Adjust glucocorticoid dosing in pediatric patients to avoid both hypoadrenalism and an inhibitory effect on growth ( 7 Cytochrome P450-Metabolized Drugs: SKYTROFA may alter the clearance. Monitor carefully if used with SKYTROFA ( 7 Oral Estrogen: Larger doses of SKYTROFA may be required ( 7 Insulin and/or Other Antihyperglycemic Agents: Dose adjustment of insulin or antihyperglycemic agent may be required ( 7.

Quick Reference Guide
Skytrofa registered Single-patient use This is your Quick Reference Guide Read your Instructions for Use for full instructions before using this Quick Reference Guide. For training video, go to www. com If you are unsure about your dose, contact your healthcare provider. Instructions for Use Quick Reference Guide Training Video Ascendis Pharma Customer Support 1-844-44ASCENDIS # 02 2025-07-18 8020100531_05 Parts overview Constant green Flashing green Flashing orange Quick troubleshooting For all troubleshooting cases and details, see Instructions for Use (IFU) Charging required (Step 2) If the battery level is low: You will see a flashing orange battery icon. Do this: SKYTROFA Auto-Injector not upright (Step 4 and 6. 1) If the SKYTROFA Auto-Injector is not in an upright position during mixing and air removal: You will hear a repeating notification sound. Mixing icon will flash slowly and progress bar will freeze. Do this: Skin contact lost (Step 9) If the green top is removed from skin before the injection is complete: You will hear a repeating notification sound. Check mark icon will flash slowly and progress bar will freeze. Do this: Prepare 1 Check and assemble cartridge and needle 1. 3 Check expiration date and cartridge dose on cartridge pack. If refrigerated, allow 15 Screw needle straight and tightly on cartridge. Do not Remove paper from needle. 2 Turn on the auto-injector (You will hear 2 3 Insert cartridge with attached needle 3. 3 Mix 4 Wait while mixing Wait 4 to 8 minutes for the auto-injector to mix medicine. 2 If your auto-injector turns off automatically read Instructions for Use 5 Turn the auto-injector up and down Turn the auto-injector up and down, listening Turn up and down correctly 2 loud beeps Do not If you see a flashing orange mixing icon read 6 Finish mixing 6. 2 Keep the auto-injector upright on a flat surface until you hear 2 Inject 7 Check mixed medicine 8 Prepare for injection 8. 3 Choose an injection site: Make sure your hands are clean using soap and water or hand sanitizer. Clean injection site with alcohol wipe. Do not 9 Inject medicine 9. 2 After injection 10 Remove cartridge 10. 2 11 Check cartridge and throw away 12 Store the auto-injector Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image.">OVERDOSAGE
Acute overdosage may lead initially to hypoglycemia and subsequently to hyperglycemia. Overdose with somatropin may cause fluid retention. Long-term overdosage may result in signs and symptoms of gigantism consistent with the known effects of excess growth hormone.
NONCLINICAL TOXICOLOGY
Carcinogenicity studies have not been conducted with lonapegsomatropin-tcgd. Lonapegsomatropin-tcgd was not mutagenic in the Ames test, in the human chromosomal aberration assay or in the rat bone marrow micronucleus test. In an animal fertility study, lonapegsomatropin-tcgd was administered via subcutaneous injection to male and female rats before cohabitation, through mating to implantation. Lonapegsomatropin-tcgd did not affect fertility or early embryo-fetal development at doses up to 20-fold the clinical pediatric dose of 0.24 mg/kg/week and approximately 46-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg hGH/week.
CLINICAL STUDIES
A multi-center randomized, open-label, active-controlled, parallel-group phase 3 study was conducted in 161 treatment-naïve, prepubertal pediatric subjects with growth hormone deficiency (GHD); 105 subjects received once-weekly SKYTROFA, and 56 received daily somatropin. The dose in both arms was 0. 24 mg/kg/week. The primary efficacy endpoint was annualized height velocity at Week 52. The subjects ranged in age from 3. 1 years with a mean of 8. One hundred thirty-two (82%) subjects were male and 29 (18%) were female. One subject was Asian, three were Black or African American, 152 were Caucasian, and five were categorized as "other. " The subjects had a mean baseline height SDS (standard deviation score) of -2. Treatment with once-weekly SKYTROFA for 52 weeks resulted in an annualized height velocity of 11. Subjects treated with daily somatropin achieved an annualized height velocity of 10. 3 cm/year after 52 weeks of treatment. Refer to Table 5. Table 5: Annualized Height Velocity at Week 52 in Pediatric Treatment-Naïve Subjects with Growth Hormone Deficiency Once-Weekly SKYTROFA (N = 105) Daily Somatropin (N = 56) Estimate of Treatment Difference (95% CI) (SKYTROFA minus Daily Somatropin) Annualized Height Velocity (cm/year) The estimates of least squares (LS) means and 95% confidence interval (CI) are from an ANCOVA model that included baseline age, peak GH levels (log transformed) at stimulation test, baseline height SDS en dash average SDS of parental height as covariates, and treatment and sex as factors. Missing data were imputed with multiple imputation method. 9 Height SDS (change from baseline) was 1. 1 in the SKYTROFA arm and 0. 96 in the daily somatropin arm at Week 52. Refer to Table 6. Table 6: Height SDS over 52 Weeks in Pediatric Treatment-Naïve Subjects with Growth Hormone Deficiency Once-Weekly SKYTROFA Daily Somatropin Abbreviations: SDS, standard deviation score. Height SDS, baseline -2. 0 Height SDS, change from baseline Height SDS, change from baseline: The estimates of LS means are from an ANCOVA model that included baseline age, peak GH levels (log transformed) at stimulation test and baseline height SDS as covariates, and treatment and sex as factors. 96 A multi-center, randomized, parallel-group, placebo-controlled (double-blind), phase 3 study was conducted in 259 adults with GHD. Eighty-nine subjects received once-weekly SKYTROFA, 84 subjects received once-weekly placebo, and 86 subjects received open-label daily somatropin. The mean (range) age at enrollment was 43 (23 to 81) years old, with 119 (46%) females (55 on oral estrogen) and 140 (54%) males, and the (SD) baseline body mass index of 28 (6. 3) kg/m 2 The primary efficacy endpoint, change in trunk percent (%) fat was measured by dual X-ray absorptiometry from baseline to Week 38 in the SKYTROFA group, compared to the placebo group (see Table 7 Table 7: Change in Trunk Percent Fat from Baseline After 38 Weeks of Treatment in Adults with Growth Hormone Deficiency en dash SKYTROFA vs. Placebo Change from Baseline at Week 38 Once-Weekly SKYTROFA Once-Weekly Placebo LS Mean Difference [95% CI] P-value Abbreviations: LS, least squares; CI, confidence interval; kg, kilogram. Trunk percent fat (%) The estimates of least square (LS) means and 95% confidence interval (CI) are from an ANCOVA model that included treatment arm, region (North America, Europe, Asia-Pacific), baseline age group, gender, concomitant oral estrogen at screening (yes vs. no), and adult GHD onset (adult vs. childhood) and corresponding baseline variable as a covariate. 0001 Patients treated with daily somatropin achieved a change in trunk percent fat of -3. 1% after 38 weeks. No formal statistical comparison between SKYTROFA and daily somatropin was conducted. Change in total body lean mass and trunk fat mass from baseline after 38 weeks of treatment were secondary efficacy endpoints. At 38 weeks, the change from baseline in total body lean mass was +1. 6 kg for lonapegsomatropin and -0. 1 kg for placebo (LS mean difference of 1. 7 kg with 95% CI of 1. 5, p-value < 0. At 38 weeks, the change from baseline in trunk fat mass was -0. 5 kg for lonapegsomatropin and +0. 2 kg for placebo (LS mean difference of -0. 7 kg with 95% CI of -1. 2, p-value = 0. After 38 weeks, SKYTROFA treatment in adults with GHD resulted in normalization of IGF-1 SDS to 1. 4 compared to -2. 6 in placebo-treated patients. See Table 8 Table 8: IGF-1 SDS at Baseline and after 38 Weeks of Treatment in Adults with Growth Hormone Deficiency en dash SKYTROFA vs. Placebo Time Point Once-Weekly SKYTROFA Once-Weekly Placebo Abbreviations: SD, standard deviation; SDS, standard deviation score. Baseline IGF-1 SDS, mean (SD) -2. 2) Week 38 IGF-1 SDS, mean (SD) Sampling time corresponded to weekly average IGF-1 SDS for SKYTROFA. 3) The mean (SD) IGF-1 SDS level in daily somatropin treated patients was -2. 82 (1) at baseline and 0. 98) at 38 weeks.
Quick Reference Guide
Skytrofa registered Single-patient use This is your Quick Reference Guide Read your Instructions for Use for full instructions before using this Quick Reference Guide. For training video, go to www. com If you are unsure about your dose, contact your healthcare provider. Instructions for Use Quick Reference Guide Training Video Ascendis Pharma Customer Support 1-844-44ASCENDIS # 02 2025-07-18 8020100531_05 Parts overview Constant green Flashing green Flashing orange Quick troubleshooting For all troubleshooting cases and details, see Instructions for Use (IFU) Charging required (Step 2) If the battery level is low: You will see a flashing orange battery icon. Do this: SKYTROFA Auto-Injector not upright (Step 4 and 6. 1) If the SKYTROFA Auto-Injector is not in an upright position during mixing and air removal: You will hear a repeating notification sound. Mixing icon will flash slowly and progress bar will freeze. Do this: Skin contact lost (Step 9) If the green top is removed from skin before the injection is complete: You will hear a repeating notification sound. Check mark icon will flash slowly and progress bar will freeze. Do this: Prepare 1 Check and assemble cartridge and needle 1. 3 Check expiration date and cartridge dose on cartridge pack. If refrigerated, allow 15 Screw needle straight and tightly on cartridge. Do not Remove paper from needle. 2 Turn on the auto-injector (You will hear 2 3 Insert cartridge with attached needle 3. 3 Mix 4 Wait while mixing Wait 4 to 8 minutes for the auto-injector to mix medicine. 2 If your auto-injector turns off automatically read Instructions for Use 5 Turn the auto-injector up and down Turn the auto-injector up and down, listening Turn up and down correctly 2 loud beeps Do not If you see a flashing orange mixing icon read 6 Finish mixing 6. 2 Keep the auto-injector upright on a flat surface until you hear 2 Inject 7 Check mixed medicine 8 Prepare for injection 8. 3 Choose an injection site: Make sure your hands are clean using soap and water or hand sanitizer. Clean injection site with alcohol wipe. Do not 9 Inject medicine 9. 2 After injection 10 Remove cartridge 10. 2 11 Check cartridge and throw away 12 Store the auto-injector Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image.

Ascendis Pharma Endocrinology, Inc.

SKYTROFA- lonapegsomatropin-tcgd_injection, powder, lyophilized, for solution Product manual source documgent