Yuviwel

Yuviwel (navepegritide) is used to increase linear growth (height) in children 2 years of age and older with achondroplasia whose growth plates (epiphyses) are still open. It is given once a week as an injection under the skin (subcutaneously).

Yuviwel is a C-type natriuretic peptide (CNP) analog. It is a prodrug that slowly releases active CNP over the week, which allows once-weekly dosing.

The dose of Yuviwel is based on your child's body weight. Your child's healthcare provider will check their growth regularly and adjust the dose as their weight changes. Yuviwel will be stopped once it is confirmed that your child has no further growth potential, shown by closure of the growth plates.

Yuviwel gained FDA approval on February 27, 2026. It was granted accelerated approval based on an improvement in annualized growth velocity (how fast a child grows in a year). Continued approval may depend on results from confirmatory clinical trials.

The safety and effectiveness of Yuviwel have not been established in children under 2 years of age.

Achondroplasia is caused by a gain-of-function change in the FGFR3 gene (fibroblast growth factor receptor 3). This makes FGFR3 signaling overactive, which slows endochondral ossification, the process by which cartilage in the growth plates is turned into bone. The result is short stature and other skeletal changes.

Yuviwel contains navepegritide, a form of CNP attached to a carrier by a TransCon linker. After injection, the linker breaks down steadily, releasing CNP continuously over the weekly dosing interval. The released CNP has the same receptor binding and activity as the body's own CNP.

CNP binds to natriuretic peptide receptor-B (NPR-B). This increases cyclic guanosine monophosphate (cGMP) and signals through protein kinase G, which blocks the MAPK signaling pathway and counteracts the overactive FGFR3 signaling. This helps cartilage cells (chondrocytes) in the growth plates to multiply and mature, stimulating bone growth.

The effectiveness of Yuviwel was shown in a randomized, double-blind, placebo-controlled trial (Trial 1; NCT05598320) in 84 children with genetically confirmed achondroplasia who had not received treatment before. Children were aged 2 to 12 years (average age 5.7 years) and received either navepegritide 0.1 mg/kg once weekly (57 children) or placebo (27 children) for 52 weeks.

The main result measured was annualized growth velocity (AGV) at week 52.

A height Z-score shows how a child's height compares with a reference group. The achondroplasia-specific score compares children with untreated children who have achondroplasia.

Improvements were seen across all age, sex, and region subgroups. The difference in AGV was 1.0 cm/year in children younger than 5 years and 1.8 cm/year in children 5 years and older.

In a second, dose-finding trial (Trial 2; NCT04085523), all 57 children continued into an open-label extension. Growth velocity was maintained in children who received 2 years of treatment with navepegritide 0.1 mg/kg once weekly.

Yuviwel is given by subcutaneous (under the skin) injection once a week, on the same day each week, at any time of day. The dose is based on your child's body weight.

• Before giving Yuviwel, you or a caregiver should be trained by a healthcare provider on how to prepare and inject it, using the Yuviwel Instructions for Use (available at www.Yuviwel.com).
• You can also call Ascendis Pharma Customer Support toll-free at 1-844-442-7236 (1-844-44ASCENDIS) for help or additional training.
• Refer to the Instructions for Use that come with Yuviwel for complete instructions with illustrations.

Preparing Yuviwel

• If refrigerated, let the vial and the prefilled diluent syringe reach room temperature (about 30 minutes) before starting.
• Screw a preparation needle onto the diluent syringe and inject all of the diluent into the vial. Shake the vial up and down for 15 seconds. Do not swirl or roll. Let the vial stand at room temperature for 5 minutes. Throw away the diluent syringe and needle right away.
• Check the solution. It should be clear and colorless. Do not use it if it is discolored, cloudy, or has visible particles. Air bubbles are normal.
• Screw a new preparation needle onto the injection syringe and draw up the prescribed dose. Remove any air, then check that the dose is still correct.
• Remove and throw away the preparation needle, then screw the injection needle onto the injection syringe.

Once mixed, Yuviwel can be kept at room temperature up to 86°F (30°C) for up to 4 hours.

Injecting Yuviwel

• Inject into the stomach area (abdomen), 2 inches away from the belly button, or the thighs. If a caregiver is giving the injection, the buttocks or back of the upper arm can also be used.
• Rotate injection sites each time. Do not inject into any other areas. Avoid skin that is red, swollen, or scarred.
• Children weighing 56 kg or more need a dose of more than 1 mL, which requires 2 kits. Give the 2 injections one after the other, at different injection sites.
• Do not draw up more than 1 dose from a vial. All components are for single use only. Throw away any unused solution.
• Only use the vial, needles, and syringes supplied in the Yuviwel kits, and do not use them for other medicines.

There are no conditions listed in the prescribing information under which Yuviwel must not be used (no contraindications). Before your child starts Yuviwel, tell their healthcare provider about all of their medical conditions, including if they have:

• Kidney problems. Yuviwel is not recommended for people with moderate or severe kidney problems (eGFR below 60 mL/min/1.73 m2). No dose change is needed for mild kidney problems.
• Heart or blood vessel disease, or low blood pressure.

Also tell the healthcare provider about all medicines your child takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Pregnancy

There are no data on the use of Yuviwel in pregnant women. In animal studies, navepegritide given during pregnancy did not affect fetal survival or cause birth defects at doses giving up to 7 to 10 times the exposure of the maximum recommended human dose.

Achondroplasia is an autosomal dominant genetic condition. A parent with achondroplasia has a 50% chance of having a child with achondroplasia.

Breastfeeding

It is not known if navepegritide passes into breast milk. Because it is a large molecule, only low amounts are expected to pass into milk, and little is expected to be absorbed by a breastfed baby. Talk to your healthcare provider about the benefits and risks of breastfeeding while using Yuviwel.

Common side effects

The most common side effects of Yuviwel, reported in at least 5% of children and more often than with placebo, were:

Injection-site reactions included swelling, redness, bruising, itching, discoloration, bleeding, pain, blisters, and fluid buildup at the injection site. Rotating the injection site each time can reduce the risk of injection-site reactions.

Increased hair growth (hypertrichosis) was reported in 3% of children receiving Yuviwel and none receiving placebo. This appeared as hair growth at injection sites or more body hair on the limbs, back, or shoulders. Rotating the injection site with each dose can reduce the risk of local skin changes.

Some children develop antibodies to navepegritide or CNP. In clinical trials, 30% of children treated for up to 3 years developed antibodies, which were found at low levels for a short time. No effect on how well Yuviwel worked or on its safety was identified.

Serious side effects

• Low blood pressure. Short-term drops in blood pressure have been reported with a once-daily CNP analog. Children with significant heart or blood vessel disease were not included in Yuviwel clinical trials. Contact your child's healthcare provider if your child has symptoms of low blood pressure, such as dizziness, tiredness, or nausea, while being treated with Yuviwel.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or to Ascendis Pharma at 1-844-442-7236.

Usual pediatric dose for achondroplasia (2 years and older)

Yuviwel is given once weekly by subcutaneous injection. The dose is based on body weight:

After mixing, the concentration is 2.2 mg/mL in the 1.3 mg vial, 4.6 mg/mL in the 2.8 mg vial, and 5.5 mg/mL in the 5.5 mg vial.

Switching from a daily CNP analog

Start once-weekly Yuviwel on the day after the last dose of daily CNP therapy.

• If a dose is missed, give it as soon as possible, but no more than 2 days after the missed dosing day.
• If more than 2 days have passed, skip the missed dose and give the next dose on the regular dosing day.
• To avoid missing a dose, Yuviwel can be given up to 2 days before or 2 days after the scheduled dosing day. Then return to the usual dosing day for the next dose.
• At least 5 days must pass between doses. If you want to change your child's regular dosing day, make sure at least 5 days pass between the last dose and the new dosing day.

No studies have been done to see how navepegritide interacts with other medicines. Tell your child's healthcare provider about all medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal products.

Yuviwel is supplied as a white to off-white powder in a single-dose vial for mixing, in 3 strengths:

• 1.3 mg vial (yellow cap)
• 2.8 mg vial (blue cap)
• 5.5 mg vial (violet cap).

Each carton contains 4 kits. Each kit contains 1 vial, 1 prefilled diluent syringe of Sterile Water for Injection (0.8 mL for the 1.3 mg and 2.8 mg vials, 1.1 mL for the 5.5 mg vial), 2 preparation needles, 1 injection syringe, and 1 injection needle.

• Store Yuviwel in the refrigerator between 36°F and 46°F (2°C and 8°C).
• Keep in the original packaging until time of use to protect from light. Do not freeze.
• Yuviwel can also be stored at room temperature up to 86°F (30°C) for up to 6 months, and can be returned to the refrigerator within those 6 months.
• Do not use Yuviwel after the expiration date or 6 months after the date it was first taken out of the refrigerator, whichever comes first.
• Mixed Yuviwel can be kept at room temperature up to 86°F (30°C) for up to 4 hours. Throw away any unused mixed solution.

Active ingredient: navepegritide

Inactive ingredients: succinic acid, trehalose dihydrate, tromethamine, and hydrochloric acid.

Diluent: Sterile Water for Injection, supplied in a prefilled syringe.