1 INDICATIONS AND USAGE 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 )

6 ADVERSE REACTIONS 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%).

g Injection site reaction in the SOGROYA treatment group included injection site bruising (6.1%) and injection site hemorrhage (2%) h Abdominal pain in the SOGROYA treatment group included abdominal distension (2%) Pediatric Patients with Growth Failure Associated with Idiopathic Short Stature 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 ISS compared to somatropin 0.05 mg/kg/day [see Clinical Studies (14.4)] .

Table 5 shows the adverse reactions occurring at ≥10% in the ISS cohort with 87 pediatric patients.

Table 5.

Adverse Reactions Occurring ≥10% in SOGROYA or Somatropin-Treated Pediatric Patients with ISS at Week 52 Somatropin 0.05 mg/kg/day (N=28) SOGROYA 0.24 mg/kg/week (N=59) Adverse Reactions % % Respiratory Tract Infection a 29 31 Nasopharyngitis b 21 22 Ear Infection c 7 12 Diarrhea d 25 10 Headache 11 10 Injection site reaction e 7 10 Cough f 11 5 Vomiting g 11 5 a Respiratory tract infection in the SOGROYA treatment group included influenza (16.9%), upper respiratory tract infection (6.8%), respiratory tract infection (3.4%), pneumonia (1.7%), pneumonia bacterial (1.7%), respiratory tract infection viral (1.7%), and viral upper respiratory tract infection (1.7%).

b Nasopharyngitis in the SOGROYA treatment group included nasopharyngitis (15.3%), pharyngitis streptococcal (5.1%), pharyngitis (1.7%), rhinitis (1.7%), sinusitis (1.7%), and tracheitis (1.7%).

c Ear infection in the SOGROYA treatment group included otitis media (6.8%), ear infection (3.4%), and otitis media acute (1.7%).

d Diarrhea in the SOGROYA treatment group included gastroenteritis (3.4%), gastroenteritis viral (3.4%), diarrhea (1.7%), enterobiasis (1.7%), and parasitic gastroenteritis (1.7%).

e Injection site reaction in the SOGROYA treatment group included application site reaction (1.7%), injection site bruising (1.7%), injection site hematoma (1.7%), injection site hemorrhage (1.7%), injection site pruritis (1.7%), and injection site urticaria (1.7%).

f Cough in the SOGROYA treatment group included cough (5.1%).

g Vomiting in the SOGROYA treatment group included vomiting (5.1%).

Description of Select Adverse Reactions Adenoidal and tonsillar hypertrophy was reported in 1 (2%) subject with ISS in the first year of treatment with SOGROYA who received tonsillectomy and adenoidectomy.

The adenoidal and tonsillar hypertrophy resolved after the procedure.

Adult Patients with GHD SOGROYA was studied in adult patients with GHD in a 35-week, placebo-controlled, double-blind trial with an active-control arm [see Clinical Studies ( 14.5 )] .

Adverse reactions occurring >2% with SOGROYA are presented in Table 6 .

Table 6.

Adverse Reactions Occurring >2% in Adults with GHD Treated with SOGROYA and More Frequently # than in Placebo-Treated Patients for 34 Weeks Placebo (N=61) SOGROYA (N=120) Adverse Reactions % % Back pain 3.3 10 Arthralgia 1.6 6.7 Dyspepsia 3.3 5 Sleep disorder 1.6 4.2 Dizziness 1.6 4.2 Tonsillitis 1.6 3.3 Peripheral edema 1.6 3.3 Vomiting 1.6 3.3 Adrenal insufficiency 1.6 3.3 Hypertension 1.6 3.3 Blood creatine phosphokinase increase 0 3.3 Weight increased 0 3.3 Anemia 0 2.5 # Included adverse reactions reported with at least 1% greater incidence in SOGROYA group compared to the placebo group More SOGROYA treated patients shifted from normal baseline levels to elevated phosphate and creatine phosphokinase levels at the end of the trial compared to the placebo group (17.5% vs 4.9% and 9.2% vs.

6.6%, respectively); these laboratory changes occurred intermittently, and were non-progressive.

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of somatropins.

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.

Musculoskeletal and connective tissue disorders – osteonecrosis in pediatric patients.