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.

The right diagnosis made an incredible difference in my life.

Mary, a person living with NAGS Deficiency

This is an actual patient story, but the patient’s name has been changed and a stock photo has been used to protect her privacy.

A patient story

A community and a path to the future

Mary, like many other twenty-somethings, is a full-time student working toward a master’s degree and has two part-time jobs. Ten years ago, when she was in the hospital yet again with symptoms she had been experiencing periodically her entire life, she would not have thought this would be possible.

READ MARY'S STORY

Mary has an extremely rare urea cycle disorder called NAGS (N-acetylglutamate synthase) deficiency. The disorder partially or entirely blocks the body’s natural process to eliminate excess ammonia, which leads to high ammonia build-up in the blood. This is dangerous because high blood ammonia can be extremely toxic to the central nervous system.
Mary’s journey to the right diagnosis would span 18 years, many hospitalizations, and thousands of miles.

“Babies are supposed to sleep”

Born in Belarus, Mary was a lethargic baby who tended to avoid foods containing protein as she grew. Mary’s mother, a physician, suspected something was wrong, but doctors “told her she was crazy,” says Mary. “They said, ‘Babies are supposed to sleep.’ ”
Severe symptoms, including confusion and inability to focus, a “foggy brain” feeling, and irritability, led to a hospitalization when Mary was 10 years old. By then, the family had moved to the United States. A doctor checked Mary’s ammonia level, which was high, and a diagnosis was made: OTC (ornithine transcarbamylase) deficiency, a different urea cycle disorder than NAGS deficiency that can also cause high blood ammonia levels. Mary began taking a medication commonly prescribed for OTC deficiency. “It helped with some of my symptoms,” she says. But despite taking the medicine and eating a very low-protein diet, “I still ended up in the hospital pretty often.”

Added stress during her freshman year of college

Like many freshmen, Mary was excited about college, but her unpredictable symptoms caused anxiety. “I felt like I was always in crisis mode,” she says. “I knew I could feel fine one day and be in the hospital the next day.”
One night after she and a friend had eaten at a restaurant, she vomited at a grocery store. By then she knew the drill. “I had to call my mom because I couldn’t even drive myself to the hospital,” she says. “I felt like my adulthood was being taken away from me.”

Mary recalls, “I was crying, thinking about how maybe the hospitalizations would continue, how my college studies and friendships would be affected.” She had only ever told her closest friends about her condition because it was hard to describe and she didn’t want it to define her.

A clinical trial: help for Mary at last

Neither Mary’s family nor her team of doctors had given up trying to find an answer to her continuing symptoms. And it was right before her final hospitalization during her freshman year that they found one, although it would be months before the answer could be verified and fully realized.

Mary’s doctors told the family about a treatment (now known as CARBAGLU® or carglumic acid) that was being investigated for urea cycle disorders including NAGS deficiency. Her doctors explained the potential risks and benefits of the medication. In Mary’s case, her doctors would be observing the response of someone with OTC deficiency to the medication.
CARBAGLU treatment should be managed by a physician and medical team experienced in metabolic disorders.

Mary’s parents didn’t hesitate. “My mom said, ‘If it’s available, Mary’s going to do it.’ ” Of course, they didn’t know how Mary would react to CARBAGLU. During the study, her doctors noticed that her response to CARBAGLU was consistent with how a person with NAGS deficiency would respond. Later, Mary’s new diagnosis of NAGS deficiency was confirmed. After the trial, Mary waited anxiously for months for the Food and Drug Administration (FDA) to approve CARBAGLU for the treatment of NAGS deficiency so that she could resume treatment.

A 180-degree turnaround

Things changed after Mary was correctly diagnosed with NAGS deficiency and started taking CARBAGLU. “My life improved 180 degrees,” she says. It took a few weeks to safely decrease the medicine she had been taking and increase CARBAGLU to the appropriate dose. But then she was able to start eating a normal diet without any protein restrictions, meaning no more weighing foods and counting grams of protein.

While Mary remains aware of the possible risks of taking CARBAGLU, today her biggest worries revolve around making sure she always has it with her. “I keep it at my desk at work, just in case there’s a snowstorm and I can’t get home or I forget to take it one morning when I’m in a rush,” she says. She also packs some in every bag when she travels. “But you get into a habit. Now I just get up, take my medicine, go about my day, come back home, take my medicine, go to bed, and that’s it.”

A community and a path to the future

Mary’s care is overseen by a team of healthcare professionals that includes a metabolic specialist, a metabolic dietitian, and a genetic counselor. Because she’s medically stable, Mary sees the team just once a year. But they’re always available by phone if she has questions.

Mary’s doctors have told her and her family about foundations, conferences, events, research studies, and opportunities to connect with other people who have rare metabolic conditions. Being part of a community is very important to Mary. Although she’s still anxious about what could happen in the future, she focuses on what she can control – going to her doctor appointments, learning about her condition, and pursuing her goal of becoming a mental health therapist.
“The right diagnosis made an incredible difference in my life,” she says.

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 patients 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.

READ MARY'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.

Taking CARBAGLU

It’s important to take CARBAGLU exactly as prescribed by your doctor.
Learn how to take CARBAGLU
Patient Support

Get access to financial and other support for CARBAGLU.
Access CARBAGLU resources

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.

Indications and Usage

Carbaglu^® (carglumic acid) tablets for oral suspension 200mg is a prescription drug used in all ages to help treat the following:

CARBAGLU is used to supplement standard of care treatment for acute high blood ammonia levels (hyperammonemia) due to the lack or shortage of NAGS enzyme activity.
CARBAGLU is used to maintain normal blood ammonia levels due to the lack or shortage of NAGS enzyme activity.
CARBAGLU is used to supplement standard of care treatment for acute high blood ammonia levels due to propionic acidemia (PA) or methylmalonic acidemia (MMA).

Important Safety Information

Contraindications: None.
NAGS deficiency: Most common side effects in ≥13% 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, hemoglobin decreased in red blood cells, and headache.
PA and MMA: Most common side effects in ≥5% of patients are: lower than normal white blood cells, reduced red cells in the blood, vomiting, abnormal levels of minerals in the body, decreased appetite, low blood sugar levels, lack of energy/unresponsiveness, brain disease that alters brain structure or function, and inflammation of the pancreas/increase in a type of protein made by the pancreas that helps the body digest fats.

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.

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