Somapacitan

SOGROYA is indicated for the treatment of pediatric patients aged 2.5 years and older with:

• Growth failure due to inadequate secretion of endogenous growth hormone (GH).
• Short stature born small for gestational age (SGA) and with no catch-up growth by 2 years of age.
• Growth failure associated with Noonan syndrome (NS).
• Idiopathic Short Stature (ISS). SOGROYA is indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD). SOGROYA is a human growth hormone analog indicated for: Pediatric Patients: Treatment of pediatric patients aged 2.5 years and older with:
• Growth failure due to inadequate secretion of endogenous growth hormone (GH). ( 1 )
• Short stature born small for gestational age (SGA) and with no catch-up growth by 2 years of age. ( 1 )
• Growth failure associated with Noonan syndrome (NS). ( 1 )
• Idiopathic Short Stature (ISS). ( 1 ) Adults: Replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD). ( 1 )

SOGROYA is a clear to slightly opalescent and colorless to slightly yellow solution available as follows:

• Injection: 5 mg/1.5 mL (3.3 mg/mL) in a single-patient-use prefilled pen (teal)
• Injection: 10 mg/1.5 mL (6.7 mg/mL) in a single-patient-use prefilled pen (yellow)
• Injection: 15 mg/1.5 mL (10 mg/mL) in a single-patient-use prefilled pen (red) SOGROYA is a liquid solution available in a ready-to-use prefilled pen. Injection: 5 mg/1.5 mL (3.3 mg/mL) or 10 mg/1.5 mL (6.7 mg/mL) or 15 mg/1.5 mL (10 mg/mL) in a single-patient-use prefilled pen. ( 3 )

SOGROYA is contraindicated in patients with:

• Acute critical illness after open-heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure because of the risk of increased mortality with use of pharmacologic doses of SOGROYA [see Warnings and Precautions ( 5.1 )] .
• Hypersensitivity to SOGROYA or any of its excipients. Systemic hypersensitivity reactions have been reported postmarketing with somatropin [see Warnings and Precautions ( 5.2 )] .
• Pediatric patients with closed epiphyses.
• Active malignancy [see Warnings and Precautions ( 5.3 )].
• Active proliferative or severe non-proliferative diabetic retinopathy.
• 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 risk of sudden death [see Warnings and Precautions ( 5.13 )] .
• Acute critical illness ( 4 )
• Active malignancy ( 4 )
• Hypersensitivity to somapacitan-beco or excipients ( 4 )
• Active proliferative or severe non-proliferative diabetic retinopathy ( 4 )
• Closed epiphyses in children used for longitudinal growth promotion ( 4 )
• Children with Prader-Willi syndrome who are severely obese or have severe respiratory impairment due to risk of sudden death ( 4 )

• Severe Hypersensitivity : Serious hypersensitivity reactions, including anaphylactic reactions and angioedema, may occur. In the event of an allergic reaction, seek prompt medical attention. ( 5.2 )
• Increased Risk of Neoplasm : Monitor patients with preexisting tumors for progression or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin – in particular meningiomas in patients treated with radiation to the head for their first neoplasm. ( 5.3 )
• Glucose Intolerance and Diabetes Mellitus : SOGROYA may decrease insulin sensitivity, particularly at higher doses. Monitor glucose levels periodically in all patients receiving SOGROYA, especially in patients with existing diabetes mellitus or at risk for its development. ( 5.4 )
• Intracranial Hypertension (IH) : Perform fundoscopic examinations prior to initiation and periodically thereafter. If papilledema is identified prior to initiation, evaluate the etiology and treat the underlying cause before initiating. If papilledema occurs with SOGROYA, stop treatment. ( 5.5 )
• Fluid Retention : Was observed and may be dose dependent. Reduce dose as necessary. ( 5.6 )
• Hypoadrenalism : Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism. ( 5.7 )
• Hypothyroidism : Monitor thyroid function periodically as hypothyroidism may occur or worsen after initiation of SOGROYA. ( 5.8 )
• Slipped Capital Femoral Epiphysis in Pediatric Patients : May develop. Evaluate children with the onset of a limp or persistent hip/knee pain. ( 5.9 )
• Progression of Preexisting Scoliosis in Pediatric Patients : May develop. ( 5.10 )
• Pancreatitis : Consider pancreatitis in patients with persistent severe abdominal pain. ( 5.11 )
• Lipohypertrophy/lipoatrophy : May occur if SOGROYA is administered in the same location over a long period of time. Rotate injection sites on a regular basis. ( 5.12 )

5.1 Increased Mortality in Patients with Acute Critical Illness Increased mortality has been reported after treatment with somatropin in patients with acute critical illness due to complications following open-heart surgery, abdominal surgery and multiple accidental trauma, as well as patients with acute respiratory failure [see Contraindications ( 4 )] . The safety of continuing SOGROYA treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. SOGROYA is not indicated for the treatment of non-GH deficient adults.

5.2 Severe Hypersensitivity Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin. Inform patients and/or caregivers that such reactions are possible, and that prompt medical attention should be sought if an allergic reaction occurs. SOGROYA is contraindicated in patients with known hypersensitivity to somatropin or any excipients in SOGROYA [see Contraindications ( 4 )].

5.3 Increased Risk of Neoplasms Active Malignancy There is an increased risk of malignancy progression with somatropin treatment in patients with active malignancy [see Contraindications ( 4 )] . Any preexisting malignancy should be inactive, and its treatment complete prior to instituting therapy with SOGROYA. Discontinue SOGROYA if there is evidence of recurrent activity. Risk of Second Neoplasm in Pediatric Patients In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent growth hormone deficiency (GHD) and were treated with somatropin, an increased risk of second neoplasm has been reported. Intracranial tumors, in particular meningiomas, were the most common of these second neoplasms. Monitor all patients with a history of GHD secondary to an intracranial neoplasm while on somatropin therapy for progression or recurrence of the tumor. New Malignancy During Treatment Because children with certain rare genetic causes of short stature have an increased risk of developing malignancies, thoroughly consider the risks and benefits of starting SOGROYA in these patients. If treatment with SOGROYA is initiated, carefully monitor these patients for development of neoplasms. There is risk of malignant changes of preexisting nevi with somatropin treatment in patients. Monitor patients on SOGROYA therapy carefully for increased growth or potential malignant changes of preexisting nevi. Advise patients/caregivers to report marked changes in behavior, onset of headaches, vision disturbances, and/or changes in the appearance of preexisting nevi .

5.4 Glucose Intolerance and Diabetes Mellitus Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses. New onset type 2 diabetes mellitus has been reported in patients taking somatropin. Patients with undiagnosed pre-diabetes and diabetes mellitus may experience worsened glycemic control and become symptomatic. Monitor glucose levels periodically in all patients receiving SOGROYA, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or pre-diabetes should be monitored closely. The doses of antidiabetic agents may require adjustment when SOGROYA is initiated.

5.5 Intracranial Hypertension Intracranial hypertension with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in patients treated with somatropin. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, intracranial hypertension-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose. Perform fundoscopic examination before initiating treatment with SOGROYA to exclude preexisting papilledema and periodically thereafter. If papilledema is identified prior to initiation, evaluate the etiology and treat the underlying cause before initiating SOGROYA. If papilledema is observed by fundoscopy during SOGROYA treatment, treatment should be stopped. If intracranial hypertension is confirmed, treatment with SOGROYA can be restarted at a lower dose after intracranial hypertension-associated signs and symptoms have resolved.

5.6 Fluid Retention Fluid retention was observed during SOGROYA therapy. Clinical manifestations of fluid retention (e.g. edema and nerve compression syndromes including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent.

5.7 Hypoadrenalism Patients receiving somatropin therapy who have or are at risk for corticotropin deficiency may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SOGROYA treatment. Monitor patients with known hypoadrenalism for reduced serum cortisol levels and/or need for glucocorticoid dose increases [see Drug Interactions ( 7 )].

5.8 Hypothyroidism Undiagnosed/untreated hypothyroidism may prevent an optimal response to SOGROYA. In patients with GH deficiency, central (secondary) hypothyroidism may first become evident or worsen during treatment with somatropin therapy. Therefore, patients should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.

5.9 Slipped Capital Femoral Epiphysis in Pediatric Patients Slipped capital femoral epiphysis may occur more frequently in patients undergoing rapid growth. Slipped capital femoral epiphysis may lead to osteonecrosis. […]

The following clinically significant adverse drug 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 )]
• Lipohypertrophy/Lipoatrophy [see Warnings and Precautions ( 5.12 )]
• Sudden death in pediatric patients with Prader-Willi syndrome [see Warnings and Precautions ( 5.13 )]
• Common adverse reactions reported in pediatric patients treated with SOGROYA include: cough, diarrhea, ear infection, headache, injection site reaction, nasopharyngitis, pain in extremity, pyrexia, respiratory tract infection, and vomiting. ( 6.1 )
• Adult patients with GHD: Adverse reactions reported in >2% of patients treated with SOGROYA are: back pain, arthralgia, dyspepsia, sleep disorder, dizziness, tonsillitis, peripheral edema, vomiting, adrenal insufficiency, hypertension, blood creatine phosphokinase increase, weight increase, anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience 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 trials of another drug and may not reflect the rates observed in practice. Pediatric Patients with GHD SOGROYA 0.16 mg/kg/week was studied in a 52-week randomized, open-label, active-controlled, parallel-group clinical study in 200 treatment-naïve, prepubertal pediatric patients with growth hormone deficiency [see Clinical Studies ( 14.1 )] . Table 2 shows common adverse reactions that occurred in ≥ 5% of patients treated with either SOGROYA or somatropin in this trial. Table 2. Adverse Reactions Occurring ≥5% in SOGROYA or Somatropin-treated Pediatric Patients (52 Weeks of Treatment) Somatropin (N=68) SOGROYA (N=132) Adverse Reactions % % Nasopharyngitis a 16.2

16.7 Headache 8.8

12.1 Pyrexia b 11.8

9.1 Pain in extremity c 2.9

9.8 Injection site reaction d 5.9

6.1 Diarrhea e 5.9

4.5 Nausea/vomiting f 5.9

4.5 Bronchitis 7.4 3 a Nasopharyngitis in the SOGROYA treatment group included nasopharyngitis (11.4%), rhinitis (3.8%), pharyngitis streptococcal (0.8%), acute sinusitis (0.8%), nasal congestion (0.8%), pharyngitis (0.8%), and sinusitis (0.8%). b Pyrexia in the SOGROYA treatment group included pyrexia (8.3%) and hyperthermia (0.8%). c Pain in extremity in the SOGROYA treatment group included pain in extremity (9.1%) and growing pains (0.8%). d Injection site reaction in the SOGROYA treatment group included injection site bruising (1.5%), injection site pain (1.5%), injection site hematoma (1.5%), injection site reaction (0.8%), and injection site swelling (0.8%) e Diarrhea in the SOGROYA treatment group included diarrhea (2.3%), gastroenteritis viral (1.5%), and gastrointestinal viral infection (0.8%) f Nausea/vomiting in the SOGROYA treatment group included vomiting (4.5%) and nausea (1.5%) Pediatric Patients Born Small for Gestational Age and with no Catch-up Growth by 2 Years of Age SOGROYA 0.24 mg/kg/week was studied in a 52-week randomized, open-label, active-comparator, basket clinical study in GH treatment-naïve, pre-pubertal patients with short stature born small for gestational age (SGA), Noonan syndrome (NS) or idiopathic short stature (ISS) compared to somatropin [see Clinical Studies ( 14.2 )] . Table 3 shows the adverse reactions occurring at ≥10% in the SGA cohort with 141 pediatric patients. Table 3. Adverse Reactions Occurring ≥10% in SOGROYA or Somatropin-Treated Pediatric Patients with SGA at Week 52 Somatropin 0.035 mg/kg/day (N=37) Somatropin 0.067 mg/kg/day (N=35) SOGROYA 0.24 mg/kg/week (N=69) Adverse Reactions % % % Nasopharyngitis a 38 29 26 Respiratory Tract Infection b 30 20 26 Pyrexia 16 17 19 Cough c 16 9 16 Ear Infection d 16 17 13 Diarrhea e 8 6 10 Vomiting f 11 11 10 Bronchitis 11 11 7 a Nasopharyngitis in the SOGROYA treatment group included nasopharyngitis (15.9%), pharyngitis (2.9%), rhinitis (2.9%), pharyngitis streptococcal (1.4%), sinusitis (1.4%), and viral rhinitis (1.4%). b Respiratory tract infections in the SOGROYA treatment group included upper respiratory tract infection (20.3%), influenza (10.1%), metapneuomovirus infection (1.4%), mycoplasma infection (1.4%), pneumonia (1.4%), pneumonia bacterial (1.4%), pneumonia mycoplasmal (1.4%), respiratory syncytial virus infection (1.4%), and respiratory tract infection (1.4%). c Cough in the SOGROYA treatment group included cough (15.9%). d Ear infection in the SOGROYA treatment group included otitis media (7.2%), ear infection (2.9%), otitis externa (1.4%), and otitis media acute (1.4%). e Diarrhea in the SOGROYA treatment group included diarrhea (4.3%), gastroenteritis (4.3%), and gastrointestinal viral infection (1.4%) f Vomiting in the SOGROYA treatment group included vomiting (10.1%) Description of Select Adverse Reactions Adenoidal and tonsillar hypertrophy was reported in 1 (1%) subject with SGA in the first year of treatment with SOGROYA who received tonsillectomy and adenoidectomy. The adenoidal and tonsillar hypertrophy resolved after the procedure. Pediatric Patients with Growth Failure Associated with Noonan Syndrome SOGROYA 0.24 mg/kg/week was studied in a 52-week randomized, open-label, active-comparator, basket clinical study in GH treatment-naïve, pre-pubertal patients with NS compared to somatropin 0.05 mg/kg/day [see Clinical Studies (14.3)] . Table 4 shows the adverse reactions occurring at ≥10% in the NS cohort with 77 pediatric patients. Table 4. Adverse Reactions Occurring ≥10% in SOGROYA or Somatropin-Treated Pediatric Patients with NS at Week 52 Somatropin 0.05 mg/kg/day (N=28) SOGROYA 0.24 mg/kg/week (N=49) Adverse Reactions % % Respiratory Tract Infection a 29 43 Nasopharyngitis b 25 29 Diarrhea c 14 22 Ear Infection d 14 16 Cough e 14 14 Vomiting f 11 12 Pyrexia 25 10 Headache 7 10 Injection site reaction g 14 8 Abdominal Pain h 11 2 Wound 11 0 a Respiratory tract infection in the SOGROYA treatment group included upper respiratory tract infection (20.4%), influenza (10.2%), pneumonia (6.1%), influenza like illness (2%), respiratory syncytial virus infection (2%), respiratory tract infection (2%), respiratory tract infection viral (2%), upper respiratory tract infection bacterial (2%), and viral upper respiratory tract infection (2%). b Nasopharyngitis in the SOGROYA treatment group included nasopharyngitis (24.5%), pharyngitis (4.1%), bacterial infection (2%), herpes pharyngitis (2%), pharyngitis streptococcal (2%), pharyngotonsillitis (2%), and rhinitis (2%). c Diarrhea in the SOGROYA treatment group included gastroenteritis (14.3%), diarrhea (6.1%), gastroenteritis viral (2%), and parasitic gastroenteritis (2%). d Ear infection in the SOGROYA treatment group included otitis media (8.2%), otitis externa (4.1%), ear infection (2%), otitis media acute (2%), and otitis media chronic (2%). e Cough in the SOGROYA treatment group included cough (12.2%) and bacterial infection (2%). f Vomiting in the SOGROYA treatment group included vomiting (8.2%) and gastritis (4.1%). […]

Table 7 includes a list of drugs with clinically important drug interactions when administered concomitantly with SOGROYA and instructions for preventing or managing them. Table 7. Clinically Important Drug Interactions with SOGROYA Replacement Glucocorticoid Treatment Clinical Impact: Microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. GH inhibits 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Initiation of SOGROYA may result in inhibition of 11βHSD-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 SOGROYA [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 11βHSD-1. Cytochrome P450-Metabolized Drugs Clinical Impact: Limited published data indicate that GH treatment increases cytochrome P450 (CP450)-mediated antipyrine clearance. SOGROYA may alter the clearance of compounds known to be metabolized by CP450 liver enzymes. Intervention: Careful monitoring is advisable when SOGROYA is administered in combination with drugs metabolized by CP450 liver enzymes. Oral Estrogen Clinical Impact: Oral estrogens may reduce the serum IGF-1 response to SOGROYA. Intervention: Patients receiving oral estrogen replacement may require higher SOGROYA dosages [see Dosage and Administration (2.5 )] . Insulin and/or Other Hypoglycemic Agents Clinical Impact: Treatment with SOGROYA may decrease insulin sensitivity, particularly at higher doses. Intervention: Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other hypoglycemic 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 SOGROYA. ( 7 )
• Cytochrome P450-Metabolized Drugs : SOGROYA may alter the clearance. Monitor carefully if used with SOGROYA. ( 7 )
• Oral Estrogen : Larger doses of SOGROYA may be required. ( 7 )
• Insulin and/or Other Antihyperglycemic Agents : Dose adjustment of insulin or antihyperglycemic agent may be required. ( 5.4 , 7 )

8.1 Pregnancy Risk Summary There are no available data on the use of SOGROYA during pregnancy; however, published studies describing the use of short-acting recombinant growth hormone (rhGH) during pregnancy over several decades have not identified any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, subcutaneously administered somapacitan-beco was not teratogenic in rats or rabbits during organogenesis at doses approximately 12 times the clinical exposure at the maximum recommended human dose (MRHD) of 8 mg/week. No adverse developmental outcomes were observed in a pre- and post-natal development study with administration of somapacitan-beco to pregnant rats from organogenesis through lactation at approximately 275 times the clinical exposure at the MRHD (see Data) . The background risk of birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In an embryo-fetal development study in rats, somapacitan-beco was administered by subcutaneous injection at doses of 2, 6, and 18 mg/kg/day during the period of organogenesis from gestation day 6 to 17. Fetal viability and development were not affected at doses up to 6 mg/kg/day (31 times the MRHD, based on AUC). Transient, fetal skeletal variations (short/bent/thickened long bones) were observed at 18 mg/kg/day (261 times the MRHD, based on AUC). In an embryo-fetal development study in rabbits, somapacitan-beco was administered by subcutaneous injection at doses of 1, 3, and 9 mg/kg every two days during the period of organogenesis from gestation day 6 to 18. Fetal viability and development were not adversely affected at somapacitan-beco dose of 1 mg/kg/every two days (12 times the MRHD, based on AUC). Reduced fetal growth was observed at doses ≥3 mg/kg/every two days (≥130 times the MRHD, based on C 12h ). In a pre- and post-natal development study in pregnant rats, somapacitan-beco was administered by subcutaneous injection at doses of 4, 9, and 18 mg/kg twice a week from gestation day 6 through lactation day 18. No adverse developmental effects were observed in the offspring at doses up to 9 mg/kg (275 times the MRHD, based on AUC). Increased incidence of renal pelvic dilatation was observed on post-natal day 21 at 18 mg/kg (630 times the MRHD, based on AUC), but was not observed in the adult F1 generation.

8.2 Lactation Risk Summary There is no information on the presence of somapacitan-beco in human milk, the effects on the breastfed infant, or the effects on milk production. Somapacitan-beco-related material was secreted into milk of lactating rats. When a substance is present in animal milk, it is likely that the substance will be present in human milk . Available published data describing administration of short-acting recombinant growth hormone (rhGH) to lactating women for 7 days reported that short-acting rhGH did not increase the normal breastmilk concentration of growth hormone and no adverse effects were reported in breastfed infants. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SOGROYA and any potential adverse effects on the breastfed infant from SOGROYA or from the underlying maternal condition.

8.4 Pediatric Use The safety and effectiveness of SOGROYA have been established in pediatric patients 2.5 years of age and older for the treatment of:

• Growth failure due to inadequate secretion of endogenous GH. The use of SOGROYA for this indication is supported by evidence from a 52-week randomized, multi-center, open-label, active-controlled, parallel-group phase 3 trial in 200 treatment-naïve, pediatric patients aged 2.5 to 11 years with GHD [see Clinical Studies (14.1)] . The safety profile from the pediatric trial was similar to that reported in adults [see Adverse Reactions (6.1)] .
• Short stature born SGA with no catch-up growth by 2 years of age. The use of SOGROYA for this indication is supported by evidence from a multi-center, randomized open-label, active-comparator, phase 3 basket study in 142 pediatric patients aged 2.6 to 10.7 years with short stature born SGA with no catch-up growth by 2 years of age [see Clinical Studies (14.2)] .
• Growth failure associated with NS. The use of SOGROYA for this indication is supported by evidence from a multi-center, randomized open-label, active-comparator, phase 3 basket study in 77 pediatric patients aged 2 to 11.1 years with growth failure associated with NS [see Clinical Studies (14.3)].
• ISS. The use of SOGROYA for this indication is supported by evidence from a multi-center, randomized open-label, active-comparator, phase 3 basket study in 88 pediatric patients aged 2.8 to 10.8 years with ISS [see Clinical Studies (14.4)]. The safety and effectiveness of SOGROYA have not been established in pediatric patients less than 2.5 years of age for the treatment of growth failure due to inadequate secretion of endogenous GH, short stature born SGA with no catch-up growth, growth failure associated with NS, or with ISS. Risks in pediatric patients associated with growth hormone use include:
• Sudden death in pediatric patients with Prader-Willi Syndrome. SOGROYA is not indicated for the treatment of pediatric patients with growth failure secondary to genetically confirmed Prader-Willi syndrome. [see Warnings and Precautions (5.13)]
• Increased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or head [see Warnings and Precautions (5.3)]
• 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)]

8.5 Geriatric Use In clinical studies a total of 52 (15.6%) of the 333 SOGROYA-treated patients were 65 years or older and 3 (0.9%) were 75 years or older [see Clinical Studies ( 14 )] . Subjects older than 65 years appeared to have higher exposure than younger subjects at the same dose level. Elderly patients may be more sensitive to the action of somapacitan-beco and therefore may be at increased risk for adverse reactions. Initiate SOGROYA with a dose of 1 mg once weekly and use smaller increments when increasing the dose [see Dosage and Administration ( 2.5 )].

8.6 Hepatic Impairment Adult patients: No dose adjustment of SOGROYA is required for patients with mild hepatic impairment. Higher somapacitan-beco exposure was observed in patients with moderate hepatic impairment. In patients with moderate hepatic impairment, initiate SOGROYA with a dose of 1 mg once weekly and use smaller increments when increasing the dose. The maximum dose should not exceed 4 mg once weekly. Somapacitan-beco was not studied in patients with severe hepatic impairment. Therefore, use of SOGROYA is not recommended in patients with severe hepatic impairment. [see Dosage and Administration ( 2.5 ), Clinical Pharmacology ( 12.3 )]. Pediatric patients: Based on the hepatic impairment study in adults, no dose adjustment of SOGROYA is recommended for patients with mild hepatic impairment. Higher systemic exposure of SOGROYA is expected in pediatric patients with moderate and severe hepatic impairment; therefore, SOGROYA is not recommended in these pediatric patients [see Dosage and Administration ( 2.5 )] .

Somapacitan-beco binds to a dimeric GH receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Some of these pharmacodynamic effects are primarily mediated by insulin-like growth factor-1 (IGF-1) produced in the liver, while others are primarily a consequence of the direct effects of somapacitan-beco.