What is CARBAGLU?

CARBAGLU® (carglumic acid) is a synthetic (or man-made) form of
N-acetylglutamate (NAG)—a chemical compound your body needs to start the process of removing excess ammonia (a waste product your body produces when it breaks down proteins).

A high level of ammonia is toxic to the body. CARBAGLU helps to relieve symptoms by lowering high ammonia levels in people with NAGS deficiency.

CARBAGLU is the only FDA-approved therapy for the treatment of high ammonia levels due to NAGS deficiency in people of all ages.

Other ammonia lowering therapies such as other medications, hemodialysis and limiting protein in the diet are recommended during an acute episode.

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A patient story

Living to learn

Linden lives to learn. As a young girl and a successful student, Linden was happiest when she was growing and learning every day. Yet the simple act of going to school became a challenge because Linden has an extremely rare metabolic disease called NAGS (N-acetylglutamate synthase) deficiency.

READ LINDEN’S STORY

How does CARBAGLU work?

NAGS deficiency is a disorder that blocks or limits your body’s ability to remove excess ammonia through a process called the urea cycle. CARBAGLU can be the key to helping your body’s urea cycle function as it should.

Normally

The NAGS gene provides instructions for making the NAGS enzyme. The job of NAGS is to produce the cofactor NAG, which is the “key” that activates (or “turns on”) CPS1, the enzyme that controls the first step of the urea cycle.

When you have NAGS deficiency

Your body either produces NAGS enzyme that does not work properly or does not produce enough NAGS enzyme. As a result, your body lacks the cofactor NAG, which is the key to starting the urea cycle.

When you take CARBAGLU

The medication acts as a replacement for the cofactor NAG that your body cannot produce on its own because your body partially or completely lacks NAGS enzyme function. CARBAGLU becomes the key that turns on CPS1 and starts the urea cycle. NAG is chemically very similar to CARBAGLU. Once your urea cycle is restored, your high ammonia level will decline to a normal level.

The most common adverse reactions are vomiting, abdominal pain, fever, inflammation of the tonsils, reduced red cells in the blood, diarrhea, ear infection, infections, inflammation of the throat and nasal passages, protein molecules in red blood cells decreased, and headache.


Who should use CARBAGLU?

CARBAGLU may be used by people of all ages with high blood ammonia levels due to NAGS deficiency—from newborns to adults. CARBAGLU should be initiated as soon as the diagnosis of NAGS deficiency is suspected, which may be as soon as at birth, and managed by a physician and medical team experienced in metabolic disorders.


How well has CARBAGLU been shown to work in people with high blood ammonia levels due to NAGS deficiency?

Doctors have studied the effects of CARBAGLU in people with high blood ammonia levels due to NAGS deficiency. CARBAGLU has been shown to:

  • Reduce patients’ high blood ammonia levels within 24 hours.

  • Return patients’ ammonia levels to normal (based on the age of the patient) within 3 days.

  • In fact, patients treated with CARBAGLU continued to maintain normal blood ammonia levels during the analyzed period of time over an average of 8 years.

What are the possible side effects of CARBAGLU?

The most common side effects of CARBAGLU are:

  • Infections

  • Vomiting

  • Abdominal Pain

  • Fever

  • Inflammation of the tonsils

  • Reduced red cells and protein molecules in red blood cells

  • Ear infection

  • Diarrhea

  • Inflammation of the throat & nasal passages

  • Headache

Talk to your doctor about any concerns about side effects before, or during, treatment with CARBAGLU.

Now I don’t have to wait days for my
ammonia level to get back down
to the level where I can function.

Linden, a person living with NAGS Deficiency
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Living to learn

Linden lives to learn. As a young girl and a successful student, Linden was happiest when she was growing and learning every day. Yet the simple act of going to school became a challenge because Linden has an extremely rare metabolic disease called NAGS (N-acetylglutamate synthase) deficiency. The disease partially or entirely blocks the body’s natural process to eliminate excess ammonia, which leads to high ammonia building up in the blood. This is dangerous because high blood ammonia can be extremely toxic to central nervous system.

A clue from Linden’s sister

Linden began having symptoms, including headaches, vomiting, and unusual behavior, off and on when she was 10 years old. “I was having a hard time responding to my parents’ questions,” she recalls. “I was dizzy and incredibly nauseated. I felt like I was looking at things through a tunnel; they seemed far away.”

Linden’s parents took her to the hospital where her condition began to get worse. Eventually a metabolic geneticist who had diagnosed Linden’s sister with high blood ammonia shortly after birth discovered that Linden had several times the normal level of ammonia in her blood. The diagnosis of NAGS deficiency meant that Linden had to drastically change her diet. Eating foods containing protein can trigger high blood ammonia levels in patients with certain inborn errors of metabolism such as urea cycle disorders. Other triggers include illness and intense exercise.

At the time there was no effective treatment for the symptoms of NAGS deficiency, so Linden continued to have periodic symptoms that affected what she loved most: learning. “I was a good student,” she says. “But because of frequent absences due to my health, I started falling behind.”

A clinical trial: help for Linden and others

Years later, Linden learned about a clinical trial for N-carbamylglutamate (which later became known as Carbaglu® or carglumic acid), a new treatment for symptoms of NAGS deficiency. Her doctor explained the potential risks and benefits of the medication. She was cautious because she had experienced difficulties with medications in the past, but after weighing the risks and benefits, she decided to participate in the study.

CARBAGLU (carglumic acid) treatment should be managed by a physician and medical team experienced in metabolic disorders.

Normally around lunchtime Linden would feel dizzy and nauseated, but within 24 hours of taking the medication, it’s what she didn’t feel—dizziness or nausea—that got her excited. “For me, the medication started working right away,” she says. Now that she’s on appropriate therapy, “I don’t have to wait days for my ammonia level to get back down to the point where I can function, go to work, and do what I need to do.” Linden continues to see her doctor for periodic monitoring to ensure that she’s on a maintenance dose of CARBAGLU that is right for her.

While Linden remains aware of the possible risks of taking CARBAGLU, she’s thankful for a treatment that has made “all the difference in the world” by stabilizing her ammonia levels. She explains: “Taking CARBAGLU every day means that I no longer have to adhere to a strictly regimented, low-protein diet, which outside of my struggles in school was one of my biggest challenges with NAGS deficiency.” Taking CARBAGLU daily also means that Linden no longer worries about developing high ammonia and ending up in the hospital.

Armed with a treatment for the symptoms caused by NAGS deficiency, Linden continued her educational pursuits. “I wouldn’t have been able to earn a master’s degree in special education without getting my NAGS deficiency under control,” she says. “That I’m sure of.” Her goal is to ensure educational opportunities for students with disabilities, which includes advocating for the inclusive-classroom model. “I want to make a positive difference with the next generation,” she says. Enabled and inspired, Linden is still learning—and she’s inspiring others to do the same.

Indications and Usage

Carbaglu® (carglumic acid) is a prescription drug used in all ages to help treat a rare inherited disorder called NAGS deficiency, a lack or shortage of NAGS enzyme activity, which leads to high blood ammonia levels (hyperammonemia).

  • CARBAGLU is used to supplement treatment of acute hyperammonemia due to the lack or shortage of the NAGS enzyme. Other ammonia lowering therapies such as other medications, hemodialysis and limiting protein in the diet are recommended during an acute episode.
  • CARBAGLU is used to maintain normal blood ammonia levels in children and adults with NAGS deficiency. During maintenance therapy, the use of other ammonia lowering therapies and limiting protein may be needed based on plasma ammonia levels.

Important Safety Information

  • Hyperammonemia: Monitor plasma ammonia level during treatment. Prolonged exposure to elevated plasma ammonia level can result in brain injury or death. Prompt use of all therapies necessary to reduce blood ammonia level is essential.
  • Most common side effects in >9% of patients are: vomiting, abdominal pain, fever, inflammation of the tonsils, reduced red cells in the blood, diarrhea, ear infection, infections, inflammation of the throat and nasal passages, protein molecules in red blood cells decreased, and headache.
  • To report SUSPECTED SIDE EFFECTS, contact Recordati Rare Diseases Inc. at 1-888-575-8344, or FDA at 1‑800-FDA-1088 or www.fda.gov/medwatch.
  • Pregnancy: The effects of CARBAGLU on pregnancy and an unborn baby are not known.
  • Nursing Mothers: Breastfeeding is not recommended while taking CARBAGLU.
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