Zycubo (copper histidinate) is a new under-the-skin injection that the FDA has approved for treating children with a rare genetic condition that affects copper metabolism, known as Menkes disease. 

Menkes disease is caused by mutations in the copper transporter gene (ATP7A), making it hard for the body to absorb and use copper, an important mineral needed for healthy growth and development of the brain and body. Menkes disease is an X-linked recessive disease (meaning it is more common in boys and is passed through carrier mothers). Children affected by Menkes disease often have thin, light‑colored, coarse, wiry hair; weak muscles; and poor growth. They also have seizures, developmental delays, and learning difficulties and may develop serious problems affecting the brain, bones, and other vital organs.

The condition affects about 1 in 100,000-250,000 live births worldwide, and based on recent genetic data, it may happen in as many as 1 in 8,664 male births. About 90% of children have the classic form of Menkes disease and get symptoms during their infancy, rarely surviving beyond 3 years.

Zycubo is a copper replacement therapy that supplies copper in a usable (bioavailable) form to the body. It works by delivering copper directly into the body through an injection under the skin. This bypasses the faulty copper absorption process in the gut, making it easier for the body to use the copper it needs for healthy growth and development. 

This approval is important because Zycubo is the first medicine approved by the FDA to treat Menkes disease in children, giving families a new option for managing this life-threatening condition.

Why Was It Approved?

The FDA’s approval of Zycubo was based on clinical studies that showed that it was safe, well tolerated, and effective as it helped children with Menkes disease live longer.

In one study, children who started treatment within the first month of life had a 78% lower risk of death, compared to those who didn’t get the medicine. Nearly half of the children who began treatment early lived past age 6, and some lived more than 12 years. The total duration of therapy lasted up to three years. None of the children who didn’t receive treatment lived beyond age 6. Even children who started treatment later than four weeks after birth lived longer than those who didn’t receive it.

The most common side effects seen in studies included pneumonia, infections (viral, bacterial, and fungal), trouble breathing, seizures, vomiting, fever, rapid heartbeats, low blood pressure, elevated liver enzyme levels, low red blood cell counts (anemia), and reactions where the needle went in. 

What Do I Need to Know?

Zycubo is given as a shot under the skin. It needs to be mixed before use and is injected into areas like the belly, thigh, or upper arm. Avoid giving injections in places where the skin

is scarred, sore, bruised, red, or feels hardened. Caregivers can be trained to give the shots at home. Children younger than 1 year usually get it twice a day. Children ages 1-17 years typically get it once a day. If you miss a dose, give it as soon as you remember, but wait at least six hours before giving the next dose.

Before starting treatment, a health care provider will check your child’s copper levels, blood counts, and how well their liver and kidneys are working. 

Because copper can build up in the body over time, your health care provider will need to check for signs of copper overload during treatment. They may need regular blood tests to monitor copper, ceruloplasmin, and electrolyte levels; kidney and liver function; and blood counts – every six weeks for the first six months, every three months for the next 18 months, and every six months thereafter during Zycubo treatment. If abnormalities occur, dosing may be reduced, paused, or stopped, with more frequent monitoring when treatment is resumed.

Zycubo is not approved to treat a related condition called occipital horn syndrome.