Zycubo

Zycubo is a copper replacement product used to treat Menkes disease in children and adolescents. It should not be used to treat Occipital Horn Syndrome. Zycubo is given subcutaneously twice daily in children <1 year and once daily in children aged 1 to 17.

Menkes disease is a genetic disorder passed from mothers to sons that affects how the body handles copper. It's caused by mutations in the ATP7A gene, which makes a protein needed to transport copper. People with Menkes disease can't properly absorb copper from food, can't move copper into the brain, and have problems with many enzymes that need copper to function.

Zycubo (copper histidinate) gained FDA approval on January 12, 2026. Approval was based on two open-label, single-arm clinical trials that reported:

• A 78% reduction in the risk of death in children who began treatment within 4 weeks of birth
• Nearly half of early-treated patients survived beyond six years, with some exceeding 12 years
• No untreated patients survived past six years
• Later treatment also provided significant survival benefits.

Zycubo is an injection that is administered subcutaneously (under the skin). Parents and caregivers can be taught how to safely administer this medicine to their child or adolescent:

• Twice daily in children <1 year
• Once daily in children and adolescents aged 1 to 17 years.

Before your child or adolescent receives Zycubo, your healthcare provider will:

• Check their copper and ceruloplasmin levels
• Test their electrolytes, kidney function, and liver function
• Perform a complete blood count (CBC).

Your healthcare provider will continue monitoring these levels throughout treatment to watch for signs of copper buildup, which can affect your kidneys, liver, and blood cells.

Tell your healthcare provider if your child or adolescent experiences any side effects during treatment, as their dose may need to be adjusted.

Before your child or adolescent receives Zycubo, tell your healthcare provider about all their medical conditions.

Common Side Effects

The most common side effects of Zycubo injection are:

• Infections, including pneumonia
• Respiratory failure
• Seizure
• Hemorrhage (serious bleeding)
• Hypotension (low blood pressure)
• Vomiting
• Tachycardia (fast heart rate)
• Pyrexia (fever)
• Dehydration
• Fracture
• Dyspnea (shortness of breath)
• Liver enzyme increases (transaminases)
• Diarrhea
• Fungal infections
• Anemia
• Injection site reactions.

Serious Side Effects and Warnings

Zycubo may cause the following serious side effects.

Copper Accumulation and Risk of Toxicity

Zycubo treatment can cause copper to build up in the body, which may damage the kidneys, harm the liver, and affect blood cells. Your healthcare provider will monitor your child throughout treatment for drug-induced kidney injury, liver dysfunction, and hematological abnormalities, and adjust the dose of Zycubo if needed.

Notes:

Tell your healthcare provider if you have any side effect that bothers you or do not go away. These are not all of the possible side effects of Zycubo. Call your doctor for medical advice about side effects. To report suspected side effects, contact Sentynl Therapeutics, Inc. at 1-888-507-5206 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Zycubo (copper histidinate) is a copper replacement product given as an injection under the skin. This delivers copper directly into the body, avoiding the digestive system, where patients with Menkes disease cannot absorb copper properly.

Dose of Zycubo for Menkes disease

• <1 year: 1.45 mg twice daily (8 to 12 hours between injections)
• 1-17 years: 1.45 mg once daily.

Before Mixing

Store Zycubo in the refrigerator between 36°F and 46°F (2°C and 8°C).

Keep the vials of Zycubo in their original carton until you are ready to use.

After Mixing

Mix the vial of Zycubo with the sodium chloride as described in the Instructions for Use.

• Do not shake after mixing.
• Write the date and time you mixed Zycubo with 0.9% sodium chloride on the carton.

If you do not use the Zycubo solution right away after mixing, store the mixed Zycubo vial:

• In the refrigerator: between 36°F and 46°F (2°C and 8°C) and use within 24 hours. Throw away (discard) the mixed Zycubo vial if not used within 24 hours.
• At room temperature: between 68°F and 77°F (20°C and 25°C), and use within 4 hours. Throw away (discard) the mixed Zycubo vial if not used within 4 hours.

Active: copper histidinate

Supplied as a sterile, preservative-free, blue lyophilized powder or cake.

Reconstitute 1 mL sterile 0.9% Sodium Chloride Injection, USP.

Supplied as a lyophilized powder or cake in a single-dose vial for reconstitution. Contains 2.9 mg of copper histidinate (equivalent to 0.5 mg elemental copper).

Zycubo is manufactured by Zydus Lifesciences Ltd., Vadodara 391510, India for Sentynl Therapeutics, Inc., Solana Beach, CA 92075.