Ngenla

Ngenla (somatrogon-ghla) is a long-acting, once-weekly human growth hormone injection used to treat growth failure in children aged 3 years and older whose bodies do not make enough of their own growth hormone (growth hormone deficiency, or GHD). Instead of daily injections, Ngenla is given just once a week using a prefilled pen. It is approved for children only and is not indicated for adults.

Ngenla is a growth hormone analog. It binds to the growth hormone receptor and increases blood levels of insulin-like growth factor-1 (IGF-1). Growth hormone and IGF-1 together drive linear growth and metabolic changes, increasing how fast children with GHD grow. Ngenla is made by attaching small protein segments taken from human chorionic gonadotropin (hCG) to human growth hormone, which slows its clearance from the body and allows once-weekly dosing.

Ngenla received FDA approval on June 28, 2023. There is currently no Ngenla generic or biosimilar.

FDA approval was based on a 52-week, multicenter, randomized, open-label phase 3 trial (NCT02968004) in 224 treatment-naive, prepubertal children aged 3 to 12 years with GHD. Children received either once-weekly Ngenla 0.66 mg/kg or daily somatropin 0.034 mg/kg/day.

Growth with once-weekly Ngenla was similar to daily somatropin, with a treatment difference of 0.3 cm/year (95% CI -0.2 to 0.9).

Ngenla is given as a subcutaneous (under the skin) injection once a week, on the same day each week, at any time of day.

• Inject into the abdomen (at least 2 inches from the belly button), front of the thighs, buttocks, or back of the upper arms. The buttocks and upper arms are for caregiver administration only.
• Use a different injection site each week.
• Do not inject into bony areas, or skin that is bruised, red, sore, hard, scarred, or affected by a skin condition.
• The pen can be used straight from the refrigerator. For a more comfortable injection, leave it at room temperature for up to 30 minutes first.
• Your child's healthcare provider will show you how to use the prefilled pen before treatment starts.

Read the detailed Instructions for Use that come with Ngenla, or call the Ngenla helpline at 1-800-645-1280.

The day of the weekly injection can be changed if at least 3 days have passed since the previous dose. If switching from daily growth hormone, Ngenla can be started the day after the last daily injection.

Your child should not receive Ngenla if they:

• Are critically ill following open-heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure
• Have active cancer or a tumor
• Have closed bone growth plates (epiphyses)
• Have active proliferative or severe non-proliferative diabetic retinopathy (certain eye problems caused by diabetes)
• Have Prader-Willi syndrome and are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe breathing problems
• Are allergic to somatrogon-ghla or any ingredient in Ngenla.

Before starting Ngenla, tell your child's healthcare provider if your child:

• Has had heart or stomach surgery, trauma, or serious breathing problems
• Has a history of sleep apnea or breathing problems during sleep
• Has or has had cancer or any tumor
• Has diabetes
• Is pregnant, planning to become pregnant, or breastfeeding.

Ngenla has not been studied in patients with kidney or liver problems.

Pregnancy

It is not known whether Ngenla will harm an unborn baby. Talk to your child's healthcare provider if your child is pregnant or planning to become pregnant.

Ngenla may interfere with hCG-based blood and urine pregnancy tests, causing false positive or false negative results. A pregnancy test that does not rely on hCG is recommended for patients receiving Ngenla.

Breastfeeding

It is not known whether Ngenla passes into breast milk. You and your child's healthcare provider should decide whether to use Ngenla while breastfeeding.

Ngenla binds to the growth hormone receptor and activates the STAT5b signaling pathway, which increases blood levels of IGF-1. Growth hormone and IGF-1 stimulate linear growth and metabolic changes and increase growth velocity in children with GHD.

Ngenla is a fusion protein made of human growth hormone with one copy of the C-terminal peptide (CTP) from the beta chain of hCG attached at one end and two copies at the other. This larger protein is cleared from the body more slowly than standard growth hormone, with an effective half-life of about 38 hours. IGF-1 levels peak about 2 days after each dose.

Most children treated with Ngenla develop antibodies to it (77% in the main study), and a small number (3.7%) developed neutralizing antibodies. These antibodies did not appear to affect safety, effectiveness, or growth.

The most common side effects of Ngenla, reported in 5% or more of children in the clinical trial, are shown below alongside daily somatropin.

Injection site reactions were more common with Ngenla than with daily somatropin. They included injection site pain (39% vs 25%), swelling or hardening (10% vs 1%), redness (8% vs none), itching (5% vs none), and bleeding (5% vs none).

More children treated with Ngenla had raised eosinophil (a type of white blood cell) levels at the end of the study than with daily somatropin (29% vs 12%).

Since approval, loss of fat tissue under the skin at the injection site (lipoatrophy), slipped capital femoral epiphysis, and osteonecrosis in children have been reported with Ngenla or somatropin products.

This is not a complete list of side effects. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or to Pfizer at 1-800-438-1985.

Increased risk of death in critical illness

Ngenla must not be used in children who are critically ill following open-heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure. Increased mortality has been reported in critically ill patients treated with somatropin.

Sudden death in children with Prader-Willi syndrome

Ngenla is not indicated for children with growth failure due to genetically confirmed Prader-Willi syndrome. There have been reports of sudden death in children with Prader-Willi syndrome who started somatropin and had one or more of these risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Males with one or more of these risk factors may be at greater risk than females.

Serious allergic reactions

Serious allergic reactions, including anaphylaxis and angioedema, have been reported with somatropin. Get emergency medical help right away if your child develops swelling of the face, lips, mouth, or tongue; trouble breathing; wheezing; severe itching; skin rashes, redness, or swelling; dizziness or fainting; a fast heartbeat or pounding in the chest; or sweating.

Cancer and tumors

Ngenla may increase the growth of existing tumors and should not be started until any cancer is inactive and its treatment is complete. Childhood cancer survivors who received radiation to the brain or head and later developed GHD have a higher risk of a second tumor, most commonly meningiomas. Children with certain rare genetic causes of short stature also have a higher risk of cancer and will be monitored carefully if Ngenla is started.

Tell your child's healthcare provider about changes in behavior, new headaches, vision changes, or changes in skin color or in the size or appearance of moles or birthmarks.

High blood sugar and diabetes

Ngenla can reduce insulin sensitivity, particularly at higher doses, and new-onset type 2 diabetes has been reported with growth hormone. Blood sugar will be checked periodically, especially in children with obesity, Turner syndrome, or a family history of diabetes. Doses of insulin or other diabetes medicines may need adjustment.

Increased pressure in the skull (intracranial hypertension)

Increased pressure inside the skull has been reported with somatropin, usually within the first 8 weeks of treatment. A fundoscopic (eye) exam is needed before starting Ngenla and periodically during treatment. Tell your child's healthcare provider about headaches, vision changes, nausea, or vomiting.

Fluid retention

Ngenla can cause fluid retention, such as swelling in the hands and feet, joint or muscle pain, and nerve compression problems such as carpal tunnel syndrome (pain, burning, or tingling in the hands, arms, legs, or feet). These effects are usually temporary and dose-dependent.

Low cortisol (hypoadrenalism)

Ngenla can lower cortisol levels in children who have or are at risk for pituitary hormone deficiencies. Children already taking glucocorticoid replacement may need a higher maintenance or stress dose after starting Ngenla. Symptoms include severe tiredness, dizziness, weakness, vomiting, dehydration, and weight loss.

Low thyroid hormone (hypothyroidism)

Hypothyroidism may first appear or worsen during treatment and can reduce how well Ngenla works. Thyroid function will be checked periodically, and thyroid hormone replacement started or adjusted if needed.

Hip problems (slipped capital femoral epiphysis)

Children growing rapidly may develop a condition where the top of the thigh bone slips at the hip joint, which can lead to bone tissue death (osteonecrosis). Cases have been reported with Ngenla. Get medical help right away if your child develops a limp or persistent hip or knee pain.

Worsening scoliosis

Rapid growth can worsen an existing curvature of the spine (scoliosis). Growth hormone has not been shown to cause scoliosis, but children with a history of it will be monitored.

Pancreatitis

Pancreatitis has been reported with somatropin, and the risk may be greater in children than adults. Tell your child's healthcare provider about any new, persistent, severe stomach pain.

Lipoatrophy

Injecting Ngenla into the same site over a long period can cause loss of fat tissue under the skin. Rotate the injection site every week.

Changes in blood tests

Ngenla may increase blood levels of phosphorus, alkaline phosphatase, and parathyroid hormone. Your child's healthcare provider will monitor these as needed.

Ngenla treatment should be supervised by a healthcare provider experienced in diagnosing and managing children with GHD.

• Recommended dose: 0.66 mg/kg of actual body weight, injected subcutaneously once a week.
• The dose is individualized based on your child's growth response.

Ngenla pen strengths

• 24 mg/1.2 mL pen (lilac): delivers doses in 0.2 mg increments, up to 12 mg per injection
• 60 mg/1.2 mL pen (blue): delivers doses in 0.5 mg increments, up to 30 mg per injection

If a dose is more than 12 mg (24 mg pen) or 30 mg (60 mg pen), it is given as more than one injection, each at a different site. Ngenla pens are for single-patient use only. Do not share pens or needles with another person, even if the needle has been changed. The pen is not made with natural rubber latex.

Pen needles

Pen needles are not included and require a prescription. Use needles up to 8 mm long. Compatible needles are:

• 32G Novo Nordisk NovoFine Plus
• 31G Novo Nordisk NovoFine
• 31G BD Ultra-Fine or BD Micro-Fine
• 31G embecta Ultra-Fine or Micro-Fine
• Safety shield needles: 30G BD AutoShield Duo, 30G embecta AutoShield Duo, or 30G Novo Nordisk NovoFine AutoCover

If a dose is missed, give Ngenla as soon as possible within 3 days after the missed dose, then continue the regular weekly schedule. If more than 3 days have passed, skip the missed dose and give the next dose on the regularly scheduled day.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An acute overdose may first cause low blood sugar (hypoglycemia), then high blood sugar (hyperglycemia). Overdose may also cause fluid retention. Long-term overdose could cause signs of gigantism, consistent with the effects of excess growth hormone.

• Do not inject into the same site week after week
• Do not shake the pen, as shaking can damage the medicine
• Do not use Ngenla if the solution is cloudy, dark yellow, or contains flakes or particles (it should be colorless to slightly light yellow; small bubbles are normal)
• Do not use a pen that has been frozen, exposed to heat, dropped, or looks damaged
• The pen is not recommended for people who are blind or visually impaired without help from a person trained to use it.

Tell your child's healthcare provider about all medicines, vitamins, and supplements your child takes. Ngenla has the following clinically important interactions:

• Glucocorticoid replacement. Growth hormone blocks an enzyme (11-beta-hydroxysteroid dehydrogenase type 1) that converts cortisone to cortisol, so starting Ngenla may lower cortisol levels. Children taking glucocorticoid replacement may need higher maintenance or stress doses. Cortisone acetate and prednisone may be affected more than others.
• High-dose (supraphysiologic) glucocorticoids. These may reduce the growth-promoting effect of Ngenla. Glucocorticoid doses should be carefully adjusted.
• Medicines broken down by CYP450 liver enzymes. Ngenla may change how quickly these medicines are cleared. Careful monitoring is advised.
• Oral estrogen. Oral estrogen may reduce the IGF-1 response to Ngenla, so a higher Ngenla dose may be needed.
• Insulin and other diabetes medicines. Ngenla may reduce insulin sensitivity, so doses may need adjustment.

This list is not complete. Other drugs may affect Ngenla, including prescription and over-the-counter medicines, vitamins, and herbal products.

Before first use (unused pen)

• Store in the original carton, to protect from light, in a refrigerator at 36°F to 46°F (2°C to 8°C)
• Do not freeze, and do not use a pen that has been frozen
• Do not expose to heat or direct sunlight
• Unused pens may be used until the expiration date on the label if kept refrigerated.

After first use (in-use pen)

• Store in the refrigerator at 36°F to 46°F (2°C to 8°C) between injections
• Write the date of first use on the pen label, and throw the pen away 28 days after first use, even if medicine remains
• Keep the pen cap on when not in use
• Remove and safely dispose of the needle after each injection, and do not store the pen with a needle attached.

Keep Ngenla and all medicines out of the reach of children.

Active ingredient: somatrogon-ghla

Inactive ingredients: citric acid monohydrate, histidine, metacresol (as a preservative), poloxamer 188, sodium chloride, sodium citrate, water for injection.

Ngenla is a clear, colorless to slightly light yellow solution.

Ngenla is manufactured by Pfizer Ireland Pharmaceuticals Unlimited Company, Ringaskiddy, Co. Cork, Ireland, and distributed by Pfizer Labs, a division of Pfizer Inc., New York, NY. For more information, visit www.ngenla.com or call 1-800-438-1985.