Ngenla Drug Information

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.

Important Dosing and Administration Information •

NGENLA treatment should be supervised by a healthcare provider who is experienced in the diagnosis and management of pediatric patients aged 3 years and older with growth failure due to growth hormone deficiency (GHD). • Refer patient to the Instructions for Use for complete administration instructions. • Administer NGENLA by subcutaneous injection, once weekly, on the same day each week, at any time of the day in the abdomen, thighs, buttocks, or upper arms. Rotate the injection site weekly. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If flakes, particles or discoloration are observed, do not use the pen.

Do not shake; shaking can damage the product. • Prefilled pens deliver somatrogon-ghla in 0.2 mg or 0.5 mg increments.

Perform Fundoscopic Examination Prior to Initiation of NGENLA • Perform fundoscopic examination before initiating treatment with NGENLA to exclude preexisting papilledema. If papilledema is identified, evaluate the etiology and treat the underlying cause before initiating treatment with NGENLA.

Recommended Dosage and Monitoring for Pediatric Patients with GHD • Recommended dosage of NGENLA is 0.66 mg/kg based on actual body weight administered once weekly by subcutaneous (SC) injection. • Individualize dosage for each patient based on the growth response. • The day of weekly administration can be changed if necessary as long as the time between 2 doses is at least 3 days. After selecting a new dosing day, the once weekly dosing should be continued. • When switching from daily growth hormone, the once-weekly NGENLA may be initiated on the day following their last daily injection. • If more than one injection is required to deliver a complete dose, each injection should be administered at a different injection site.

Missed Dose • If a dose is missed, administer

NGENLA as soon as possible within 3 days after the missed dose. • If more than 3 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day.

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. Safety data are derived from a safety and efficacy study in pediatric patients with GHD. 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) 9 3 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%).

Postmarketing 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

• 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. Intervention: Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of NGENLA. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
• Replacement Glucocorticoid Treatment: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress dose following initiation of NGENLA.
• Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment: Adjust glucocorticoid dosing in pediatric patients to avoid both hypoadrenalism and an inhibitory effect on growth.
• Cytochrome P450-Metabolized Drugs: NGENLA may alter the clearance. Monitor carefully if used with NGENLA.
• Oral Estrogen: Larger doses of NGENLA may be required.
• Insulin and/or Other Antihyperglycemic Agents: Dose adjustment of insulin or antihyperglycemic agent may be required.

Pregnancy Risk Summary There are no available data on NGENLA use in pregnant women to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In reproduction studies with pregnant rats, there was no evidence of embryo-fetal toxicity following administration of somatrogon-ghla subcutaneously during organogenesis at doses up to 45 times the maximum recommended human dose based on exposure (see Data ). The background risk of major birth defects and miscarriage in 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 respectively. Data Animal Data In an embryo-fetal development toxicity study in rats, no adverse maternal or embryo-fetal effects were observed when somatrogon-ghla was administered via subcutaneous injection every 2 days from gestation day (GD) 6 to 18 at doses up to 30 mg/kg (45 times the maximum recommended human dose based on C av exposure). In a pre- and postnatal development study in rats, somatrogon-ghla was administered via subcutaneous injection to pregnant rats every 2 days from GD 6 to lactation day 20 at doses up to 30 mg/kg.

There was no evidence of maternal toxicity and no adverse effects on the first generation (F1) offspring. Somatrogon-ghla elicited an increase in F1 mean body weights in both sexes and increased the mean copulatory interval in F1 females at the highest dose (30 mg/kg), consistent with a longer estrous cycle length. However, there were no effects on mating indices in F1 females.

• Pediatric Use The safety and effectiveness of NGENLA have been established for the treatment of growth failure due to inadequate secretion of endogenous growth hormone (GH) in pediatric patients aged 3 years and older. The use of NGENLA for this indication is supported by evidence from a 52‑week, multi-center, randomized, open-label, active-controlled, parallel-group phase 3 study in 224 treatment-naïve, prepubertal pediatric subjects with growth hormone deficiency. Risks in pediatric patients associated with growth hormone use include:
• Increased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or head
• Slipped capital femoral epiphysis
• Progression of preexisting scoliosis
• Pancreatitis
• Sudden death in pediatric patients with Prader-Willi Syndrome. NGENLA is not indicated for the treatment of pediatric patients with growth failure secondary to genetically confirmed Prader‑Willi syndrome.

• 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.
• Hypersensitivity to somatrogon-ghla or any of the excipients in NGENLA.
• Closed epiphyses.
• Active malignancy due to the risk of malignancy progression.
• Active proliferative or severe non-proliferative diabetic retinopathy.
• 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.
• Acute critical illness.
• Hypersensitivity to somatrogon-ghla or excipients.
• Closed epiphyses.
• Active malignancy.
• Prader-Willi syndrome who are severely obese or have severe respiratory impairment.

Acute overdosage may lead initially to hypoglycemia and subsequently to hyperglycemia. Overdose with growth hormone may cause fluid retention. Long-term overdosage could result in signs and symptoms of gigantism consistent with the effects of excess growth hormone.