FDA

Ngenla

Approved 27 Jun 2023InjectionInjectable

The FDA lists this product in 2 strengths and forms.

Indications

NGENLA is indicated for the treatment of pediatric patients aged 3 years and older who have growth failure due to an inadequate secretion of endogenous growth hormone. NGENLA is a human growth hormone analog indicated for treatment of pediatric patients aged 3 years and older who have growth failure due to inadequate secretion of endogenous growth hormone ( 1 ).

Contraindications

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 somatropin [see Warnings and Precautions (5.1) ] .
Hypersensitivity to somatrogon-ghla or any of the excipients in NGENLA [see Warnings and Precautions (5.2) ].
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 [see Warnings and Precautions (5.4) ] .
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 somatrogon-ghla or excipients ( 4 ).
Closed epiphyses ( 4 ).
Active malignancy ( 4 ).
Active proliferative or severe non-proliferative diabetic retinopathy ( 4 ).
Prader-Willi syndrome who are severely obese or have severe respiratory impairment ( 4 ).

Warnings and precautions

Severe Hypersensitivity : Severe hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention ( 5.2 ).
Increased Risk of Neoplasms : 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 : NGENLA may decrease insulin sensitivity, particularly at higher doses. Monitor glucose levels periodically in all patients receiving NGENLA, especially in patients with existing diabetes mellitus or at risk for its development ( 5.4 ).
Intracranial Hypertension : Perform fundoscopic examinations prior to initiation of treatment with NGENLA and periodically thereafter. If preexisting papilledema is identified, evaluate the etiology and treat the underlying cause before initiating. If papilledema occurs with NGENLA, stop treatment ( 5.5 ).

At a glance

Brand name: Ngenla
Active substance: somatrogon-ghla
Route: Injection
Dosage form: Injectable
Applicant: Pfizer Ireland Pharmaceuticals
Status: Prescription
FDA approval: 27 Jun 2023
Application: BLA761184-002

Indications

Contraindications

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 somatropin [see Warnings and Precautions (5.1) ] .
Hypersensitivity to somatrogon-ghla or any of the excipients in NGENLA [see Warnings and Precautions (5.2) ].
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 [see Warnings and Precautions (5.4) ] .
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 somatrogon-ghla or excipients ( 4 ).
Closed epiphyses ( 4 ).
Active malignancy ( 4 ).
Active proliferative or severe non-proliferative diabetic retinopathy ( 4 ).
Prader-Willi syndrome who are severely obese or have severe respiratory impairment ( 4 ).

Warnings and precautions

Severe Hypersensitivity : Severe hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention ( 5.2 ).
Increased Risk of Neoplasms : 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 : NGENLA may decrease insulin sensitivity, particularly at higher doses. Monitor glucose levels periodically in all patients receiving NGENLA, especially in patients with existing diabetes mellitus or at risk for its development ( 5.4 ).
Intracranial Hypertension : Perform fundoscopic examinations prior to initiation of treatment with NGENLA and periodically thereafter. If preexisting papilledema is identified, evaluate the etiology and treat the underlying cause before initiating. If papilledema occurs with NGENLA, stop treatment ( 5.5 ).

Interactions

Table 2 includes a list of drugs with clinically significant drug interactions when administered concomitantly with NGENLA and instructions for preventing or managing them. Table 2 Clinically Significant Drug Interactions with NGENLA 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.

Growth hormone inhibits 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Initiation of NGENLA 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 NGENLA [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. Supraphysiologic Glucocorticoid Treatment Clinical Impact: Supraphysiologic glucocorticoid treatment may attenuate the growth-promoting effects of NGENLA in pediatric patients. Intervention: Carefully adjust glucocorticoid replacement dosing in pediatric patients receiving glucocorticoid treatments to avoid hypoadrenalism and an inhibitory effect on growth.

Cytochrome P450-Metabolized Drugs Clinical Impact: Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. NGENLA may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes. Intervention: Careful monitoring is advisable when NGENLA is administered in combination with drugs metabolized by CYP450 liver enzymes. Oral Estrogen Clinical Impact: Oral estrogens may reduce the serum IGF-1 response to NGENLA.

Intervention: Patients receiving oral estrogen replacement may require higher NGENLA dosages. Insulin and/or Other Antihyperglycemic Agents Clinical Impact: Treatment with NGENLA 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 dose following initiation of NGENLA ( 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: NGENLA may alter the clearance. Monitor carefully if used with NGENLA ( 7 ).
Oral Estrogen: Larger doses of NGENLA may be required ( 7 ).
Insulin and/or Other Antihyperglycemic Agents: Dose adjustment of insulin or antihyperglycemic agent may be required ( 5.4 , 7 ).

Adverse reactions

The following clinically significant 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 neoplasm [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 [see Warnings and Precautions (5.9) ]
Progression of preexisting scoliosis [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) ] Adverse reactions reported in ≥5% of patients treated with NGENLA are: injection site reactions, nasopharyngitis, headache, pyrexia, anemia, cough, vomiting, hypothyroidism, abdominal pain, rash, and oropharyngeal pain ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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. Safety data are derived from a safety and efficacy study in pediatric patients with GHD [see Clinical Studies (14.1) ]. The data from the 12-month main study period reflect exposure of 109 patients to NGENLA administered once weekly (0.66 mg/kg/wk) and 115 patients to somatropin administered once daily (0.034 mg/kg/day).

The mean age across the treatment groups, was 7.7 years (min 3.01, max 11.96); 40.2% of patients were >3 years to ≤7 years, 59.8% were >7 years, 71.9% of patients were male, and 28.1% were female. In this study, 74.6% of patients were White, 20.1% were Asian, 0.9% were Black or African American, 0.5% were American Indian or Alaska Native, 0.5% were Native Hawaiian or Other Pacific Islander, and for 3.6% race information was missing; 10.7% of patients identified as Hispanic or Latino.

Baseline disease characteristics were balanced across treatment groups. Table 1 shows the adverse reactions that occurred in ≥5% of patients treated with NGENLA or daily somatropin during the 12-month main study period. Reporting of injection site reactions was solicited through the use of a patient diary after each weekly injection for patients administered NGENLA and once weekly for patients administered daily injections of somatropin.

Table 1 Adverse Reactions Occurring in ≥5% of NGENLA- or Somatropin-Treated Pediatric Patients (52 Weeks of Treatment) Adverse reactions that are medically related were grouped to a single preferred term. Adverse Drug Reactions Daily Somatropin (N=115) n (%) NGENLA (N=109) n (%) Injection site reactions Injection site reactions included: injection site pain (39% somatrogon-ghla vs 25% daily somatropin), injection site swelling/induration/hypertrophy/inflammation (10% somatrogon-ghla vs 1% daily somatropin), injection site erythema (8% somatrogon-ghla vs none daily somatropin), injection site pruritus (5% somatrogon-ghla vs none daily somatropin), injection site hemorrhage (5% somatrogon-ghla vs none daily somatropin). 29 (25.2) 46 (42.2) Nasopharyngitis Nasopharyngitis included: rhinitis, pharyngitis, rhinitis allergic, pharyngitis streptococcal, viral pharyngitis, nasopharyngitis. 33 (28.7) 36 (33) Headache 25 (21.7) 18 (16.5) Pyrexia 17 (14.8) 18 (16.5) Anemia 10 (8.7) 10 (9.2) Cough 9 (7.8) 9 (8.3) Vomiting 9 (7.8) 8 (7.3) Hypothyroidism 3 (2.6) 7 (6.4) Abdominal pain 8 (7.0) 7 (6.4) Rash 7 (6.1) 6 (5.5) Oropharyngeal pain 4 (3.5) 6 (5.5) Arthralgia 8 (7.0) 5 (4.6) Otitis media 10 (8.7) 5 (4.6) Tonsillitis 6 (5.2) 5 (4.6) Bronchitis 9 (7.8) 3 (2.8) Laboratory Tests More NGENLA-treated patients shifted from normal eosinophil levels at baseline to elevated eosinophil levels at the end of the 12-month study compared to the daily somatropin group (29% vs 12%).

6.2Postmarketing Experience

The following adverse reactions have been identified during post-approval use of somatropin products or NGENLA. 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. Skin and subcutaneous tissue disorders – lipoatrophy Musculoskeletal and connective tissue disorders – osteonecrosis in pediatric patients, slipped capital femoral epiphysis

Ngenla

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Ngenla

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Increased Mortality in Patients with Acute Critical Illness

5.2Severe Hypersensitivity

5.3Increased Risk of Neoplasms Active Malignancy

5.4Glucose Intolerance and Diabetes Mellitus Treatment

5.5Intracranial Hypertension

5.6Fluid Retention

5.7Hypoadrenalism

5.8Hypothyroidism

5.9Slipped Capital Femoral Epiphysis

5.10Progression of Preexisting Scoliosis

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information