Skytrofa

Skytrofa (lonapegsomatropin-tcgd) is a once-weekly growth hormone injection used to treat pediatric growth hormone deficiency (pGHD) and adult growth hormone deficiency (GHD). It is given subcutaneously once weekly using the Skytrofa Auto-Injector. Skytrofa is preservative-free and can be stored at room temperature for up to 6 months.

Skytrofa (lonapegsomatropin-tcgd) is a long-acting prodrug of somatropin, a laboratory-made version of human growth hormone. The growth hormone is attached to a methoxypolyethylene glycol carrier by a linker that slowly breaks apart on its own after injection, releasing fully active growth hormone at a steady rate across the week. This is what allows Skytrofa to be given once weekly rather than daily. The polyethylene glycol carrier is cleared by the kidneys. Skytrofa belongs to the drug class called growth hormones.

Skytrofa first gained FDA approval on August 25, 2021. Approval was extended on July 28, 2025, to include adults with GHD. There is no generic.

• Approval in children was based on the Phase 3 heiGHt clinical trial (NCT02781727, n=161 treatment-naïve children with GHD), which demonstrated that once-weekly Skytrofa produced a higher growth rate than daily somatropin after one year in a clinical trial (11.2 vs 10.3 cm/year). Safety profiles were comparable.
• Approval in adults was based on the foresiGHt clinical trial (NCT05171855, n=259 adults with GHD), in which trunk fat fell by 2.0% with once-weekly Skytrofa and rose by 0.4% with placebo, a difference of 1.7% (p<0.0001). Total body lean mass increased by 1.6 kg with Skytrofa compared with a 0.1 kg decrease with placebo (p<0.0001).

Skytrofa is a prescription human growth hormone once-weekly injection used for:

• The replacement of growth hormone in children 1 year and older who weigh at least 26 pounds (11.5 kg) with growth hormone deficiency (GHD)
• The replacement of growth hormone in adults with growth hormone deficiency (GHD).

Skytrofa injection is given once a week under the skin of the abdomen, thigh, or buttocks using the Skytrofa autoinjector.

• The Skytrofa auto-Injector cartridges are pre-measured and ready to use, which means patients do not have to calculate or adjust doses.
• Skytrofa comes in multiple dosage strengths, which means healthcare provider can individualize the dose and adjust as needed.
• The Skytrofa Auto-Injector is reusable and rechargeable, with a full charge powering up to 4 weeks of use. The device is built to last up to 5 years or 210 injections, whichever comes first.
• It can be injected into the skin of the stomach (abdomen), thighs, or buttocks.
• Change the injection site for every injection.
• Do not inject through clothes. Inject directly into the skin.
• Do not touch the cleaned area before injecting.
• Do not fan or blow on the cleaned area.

See the Detailed Instructions for Use for the Skytrofa Auto-Injector.

Note on the auto-injector: The Skytrofa Auto-Injector is not supplied with the cartridge carton and requires a separate prescription. It is available to patients through Ascendis Pharma Customer Support by calling 1-844-442-7236 (1-844-44ASCENDIS).

Switching to Skytrofa and preparing a dose

• Switching from a daily growth hormone. Wait at least 8 hours between the final daily dose and the first Skytrofa dose.
• Switching from another weekly growth hormone. Wait at least 7 days between the final dose of the previous product and the first Skytrofa dose.
• Taking a cartridge out of the fridge. A refrigerated cartridge must sit at room temperature for 15 minutes before use.
• After mixing. Use the cartridge within 4 hours. Discard it after 4 hours at room temperature up to 86°F (30°C).
• Checking the solution. The mixed solution should be clear and colorless to slightly cloudy. Air bubbles are normal. Do not inject if the solution is cloudy or contains particles.

Do not use Skytrofa if you:

• Have a critical illness caused by certain types of heart or stomach surgery, trauma, or breathing problems
• Are allergic to somatropin or any of the ingredients in Skytrofa
• Are a child with closed bone growth plates
• Have cancer or other tumors
• Have certain types of eye problems caused by diabetes
• Are a child with Prader-Willi syndrome who is severely obese or has breathing problems, including sleep apnea (briefly stopping breathing during sleep).

Tell your healthcare provider if you are pregnant or plan to become pregnant, about all of your medical conditions, and about all the medicines you take. Skytrofa may affect how other medicines work, and other medicines may affect how Skytrofa works.

How common are Skytrofa side effects?

Children

Reported in 5% or more of children over 52 weeks, and more often than with daily somatropin.

Adults

Two side effects were reported in 5% or more of adults over 38 weeks and more often than with placebo:

• Swelling from fluid build-up, in 8% of people on Skytrofa compared with 1% on placebo
• Low thyroid hormone levels, in 7% compared with 1%. Five of the six people who developed low thyroid levels already had the condition before starting.

Blood test changes

Growth hormone treatment can raise phosphate and alkaline phosphatase levels. In the children's trial, more children on Skytrofa than on daily somatropin shifted from normal to raised phosphate (44.2% versus 30.2%) and alkaline phosphatase (19.2% versus 9.4%). In adults, 14% on Skytrofa shifted to raised alkaline phosphatase compared with 6% on placebo. These changes came and went during treatment.

Reported after approval

Severe allergic reactions, including anaphylaxis and angioedema, and osteonecrosis in children, have been reported since approval. Because these reports are voluntary, how often they happen cannot be reliably estimated.

Serious side effects

Skytrofa (lonapegsomatropin-tcgd) may cause serious side effects, including:

• Serious allergic reactions. Get medical help right away if you have swelling of the face, mouth, tongue, or throat, or trouble breathing
• High risk of death in people who have critical illnesses caused by heart or stomach surgery, trauma, or serious breathing problems
• Increased risk of growth of an existing tumor or cancer, or increased risk of a previous tumor or cancer returning in people who were treated with radiation to the brain or head as children and who developed low growth hormone problems. Your healthcare provider will need to monitor for the growth or return of a tumor or cancer. Contact your healthcare provider if you start to have sudden changes in behavior, headaches, vision problems, or changes in moles, birthmarks, or skin color
• New or worsening high blood sugar, or diabetes. Your blood sugar may need to be monitored during treatment with Skytrofa
• Increase in pressure in the skull. Contact your healthcare provider if headaches, eye problems, nausea, or vomiting occur
• Too much fluid in the body (fluid retention). Contact your healthcare provider if you notice swelling in the hands and feet, pain in the joints or muscles, or nerve problems that cause pain, burning or tingling in the hands, arms, legs, and feet
• Decrease in a hormone called cortisol. Your healthcare provider will do blood tests to check your cortisol levels. Tell your healthcare provider right away if you experience extreme fatigue, dizziness, weakness, weight loss, or darkening of the skin (hyperpigmentation).
• Decrease in thyroid hormone levels. Decreased thyroid hormone levels may affect how well Skytrofa works. Your healthcare provider will do blood tests to check your thyroid hormone levels
• Hip and knee pain or a limp in children (slipped capital femoral epiphysis). This may lead to a serious condition where bone tissue dies due to a lack of blood supply (osteonecrosis). Get medical help right away for children who develop a limp or have hip or knee pain
• Worsening of the curvature of the spine in children (scoliosis)
• Severe and constant abdominal pain. This could be a sign of pancreatitis. Tell your healthcare provider about any new abdominal pain
• Loss of fat and tissue weakness in the area of skin you or your child injects. Talk to your healthcare provider about rotating the areas where Skytrofa is injected
• High risk of sudden death in children with Prader-Willi syndrome who are severely obese or have breathing problems, including sleep apnea
• Increase in phosphate, alkaline phosphatase, and parathyroid hormone levels in your blood. Your healthcare provider will do blood tests to check this.

These are not all of the possible side effects of Skytrofa. Call your doctor for medical advice about side effects. You are encouraged to report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. You may also report side effects to Ascendis Pharma at 1-844-442-7236.

Children

In the 52-week heiGHt trial, 161 children with growth hormone deficiency who had not been treated before received either once-weekly Skytrofa or daily somatropin, both at 0.24 mg/kg per week.

The difference in height velocity was 0.9 cm/year (95% confidence interval 0.2 to 1.5) in favor of once-weekly Skytrofa. Children were aged 3.2 to 13.1 years, with an average of 8.5 years.

Adults

In the 38-week foresiGHt trial in 259 adults with growth hormone deficiency, trunk fat fell by 2.0% with Skytrofa and rose by 0.4% with placebo (difference 1.7%, p<0.0001). Total body lean mass rose by 1.6 kg with Skytrofa and fell by 0.1 kg with placebo (p<0.0001). Skytrofa also brought the average IGF-1 standard deviation score from -2.6 at baseline to 1.4 at week 38. Adults given daily somatropin had a 3.1% fall in trunk fat, but Skytrofa and daily somatropin were not formally compared.

• Before starting. An eye examination (fundoscopy) is done to rule out existing swelling of the optic nerve. If it is found, the cause must be investigated and treated before Skytrofa is started. Any existing cancer must be inactive and its treatment complete.
• IGF-1 blood levels. Used to guide dose changes. In adults, the sample is drawn 4 to 5 days after the previous dose.
• Eye examinations. Repeated periodically during treatment.
• Blood glucose. Monitored in everyone taking Skytrofa, and more closely in people with diabetes, impaired glucose tolerance, obesity or a family history of type 2 diabetes.
• Thyroid function tests. Done periodically, since untreated low thyroid levels can blunt the response to Skytrofa.
• Serum cortisol. Monitored in people with known hypoadrenalism, who may need a higher glucocorticoid replacement dose.
• Growth in children. If height velocity fails to increase, particularly in the first year, the prescriber will check adherence and look for other causes such as low thyroid levels, undernutrition, advanced bone age or antibodies to growth hormone.
• At the end of growth. Children treated for growth hormone deficiency whose growth plates have closed should be reassessed before continuing Skytrofa.

Skytrofa dose by body weight in children

Children are prescribed 0.24 mg/kg once weekly, delivered as a fixed-strength cartridge chosen by body weight.

Skytrofa dosage for adults with growth hormone deficiency

The starting dose depends on age and whether the person takes oral estrogen. The same starting doses apply to people new to growth hormone and to those switching from another growth hormone product.

The dose is increased monthly to the next cartridge strength based on response and IGF-1 blood levels, and reduced if side effects occur or IGF-1 rises above the normal range for the person's age and sex. IGF-1 blood samples are taken 4 to 5 days after the previous dose. The maximum recommended dose is 6.3 mg once weekly.

Use the medicine as soon as you can, up to 2 days before or 2 days after the scheduled dosing day. If you take the missed dose on a different day, resume once-weekly dosing on your previously scheduled day for the next dose.

If more than 2 days have passed since the scheduled dose, skip it and administer the next dose on the regularly scheduled day. At least 5 days should elapse between doses. Do not use two doses at one time.

Call your healthcare provider, seek emergency medical attention, or call the Poison Help line at 1-800-222-1222.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Other drugs may interact with Skytrofa (lonapegsomatropin-tcgd), including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Tell your doctor about all your other medicines, especially:

• Glucocorticoids (such as prednisone, cortisone, dexamethasone, methylprednisolone): Skytrofa may reduce cortisol levels. Patients taking glucocorticoids for hypoadrenalism may need an increase in their maintenance or stress doses after starting Skytrofa. In children, glucocorticoid doses should be carefully adjusted to avoid both hypoadrenalism and an inhibitory effect on growth.
• Oral estrogen or hormone replacement therapy: Oral estrogen may reduce the IGF-1 response to Skytrofa, so larger doses of Skytrofa may be required.
• Insulin or oral diabetes medicines: Skytrofa may decrease insulin sensitivity. Dose adjustments of insulin or other antihyperglycemic agents may be needed.
• Medicines metabolized by the cytochrome P450 system: Skytrofa may alter the clearance of these drugs. Careful monitoring is advisable.

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

Refrigerator storage

• Refrigerate cartridges at 36°F to 46°F (2°C to 8°C) in the outer carton to protect from light until the expiration date. Do not freeze.
• Skytrofa may be used until the expiration date when stored continuously in a refrigerator.

Room temperature storage

• Outer cartons containing blistered cartridges may be stored at room temperature (up to 86°F / 30°C) for up to 6 months and may be returned to the refrigerator within those 6 months.
• Write the date first removed from the refrigerator in the space provided on the outer carton.
• Do not use Skytrofa beyond the expiration date or 6 months after first removal from refrigeration, whichever is earlier.

Active ingredient: lonapegsomatropin-tcgd

Inactive ingredient: succinic acid, trehalose dihydrate, tromethamine (for pH adjustment), and water for injection.

Skytrofa is a white to off-white lyophilized powder available in a single-dose, dual-chamber, prefilled cartridge in the following strengths: 0.7 mg, 1.4 mg, 1.8 mg, 2.1 mg, 2.5 mg, 3 mg, 3.6 mg, 4.3 mg, 5.2 mg, 6.3 mg, 7.6 mg, 9.1 mg, 11 mg, and 13.3 mg.

Skytrofa is manufactured by Ascendis Pharma Endocrinology Division A/S, Tuborg Boulevard 12, Hellerup, Denmark DK-2900.