Innovative therapeutics



What is PKU?

PKU (Phenylketonuria) is an inherited metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). In the United States, PKU occurs in 1 in 10,000 to 1 in 15,000 newborn babies, according to the National Human Genome Research Institute. This enzyme is required for the breakdown of phenylalanine (Phe), an amino acid found in all protein-containing foods. When PAH is deficient or defective, Phe accumulates to abnormally high levels in the blood.

Clinical manifestations of sustained high Phe levels include a variety of serious neurological complications, including:

  • Intellectual disability and brain damage
  • Mood disturbances
  • Seizures and tremors
  • Cognitive problems
  • Executive function deficits

“The Pursuit of PKU” details the history of the rare condition, as well as BioMarin’s 15-year commitment to advancing the standard of care for this community, including the introduction of the first and only therapies for PKU.

Diagnosis of PKU

As a result of global newborn screening efforts implemented in the 1960s and early 1970s, virtually all people currently under the age of 40 who live in developed countries were diagnosed during the newborn period.

Managing PKU

People living with PKU struggle to manage their disease and maintain normal, non-toxic blood Phe levels with a highly Phe-restricted diet, including low-protein foods and specially formulated Phe-free medical foods. For the reasons below, this diet is very difficult to adhere to, especially through adolescence and adulthood:

    1. Phenylalanine is a component of all natural protein. Milk and dairy products, meat, fish, chicken, eggs, beans and nuts contain very high Phe levels and must be excluded from the diet. Fruits, vegetables, and breads and pastas also contain Phe, but since the Phe levels in these foods are lower, small amounts may be able to be included in the diet.

    2. Medical foods that are low in Phe and provide necessary nutrients (e.g., tyrosine) are expensive and can be unpalatable.

    3. Executive function skills are critical for appropriately managing the Phe-restricted diet. Elevated Phe may cause deficits in executive functioning, leading to a cycle of decline where levels continue to rise and disease management becomes increasingly difficult.

There are two FDA-approved treatments for PKU.

  • PALYNZIQ®(pegvaliase-pqpz) Injection, is a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 µmol/L on existing management. (See below for Important Safety Information, including Boxed Warning)
  • KUVAN® (sapropterin dihydrochloride), a therapy based on the enzyme cofactor 6R-BH4, to reduce blood Phe levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin (BH4-) responsive PKU, to be used in conjunction with a Phe-restricted diet.

Investigational Approaches for Treating PKU

Today, researchers are working to develop alternate treatment options for people living with PKU. The following are some of the approaches currently being evaluated for the treatment of PKU:

  • Gene Therapy:
    Gene therapy is being evaluated in preclinical studies as a means to allow in vivo (within a living body) production of the PAH enzyme. Like enzyme therapy, this approach is designed to address the underlying enzyme deficiency.
  • Additional Resources

    For additional information about PKU, please visit the following websites and others listed in the Patient/Physician Resource Library:

    PALYNZIQ Indication

    PALYNZIQ (Pal-lin-zeek) (pegvaliase-pqpz) Injection is a prescription medication used to lower blood levels of Phe (phenylalanine) in adults with PKU (phenylketonuria) who have uncontrolled blood Phe levels above 600 micromol/L (10 mg/dL) on their current treatment. You should discuss the potential benefits and risks of PALYNZIQ with your healthcare provider.

    PALYNZIQ Important Safety Information


    • Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment with PALYNZIQ.
    • Administer the initial dose of PALYNZIQ under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient’s and observer’s (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer auto-injectable epinephrine, if needed.
    • Prescribe auto-injectable epinephrine to all patients treated with PALYNZIQ. Prior to the first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during treatment with PALYNZIQ.
    • PALYNZIQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PALYNZIQ REMS.

    What is the most important information I should know about PALYNZIQ?

    PALYNZIQ can cause a severe allergic reaction (anaphylaxis) that may be life-threatening and can happen any time during treatment with PALYNZIQ.

    Severe allergic reactions are a serious but common side effect of PALYNZIQ

    • You will receive your first injection of PALYNZIQ in a healthcare setting where you will be closely watched for at least 1 hour after your injection for a severe allergic reaction
    • Your healthcare provider will prescribe auto-injectable epinephrine for you, and will teach you (or your caregiver) and your observer, if needed, when and how to use it if you have a severe allergic reaction
    • If you have a severe allergic reaction during treatment with PALYNZIQ, you will need to receive an injection of epinephrine immediately and get emergency medical help right away
    • Your healthcare provider will decide if you (or your caregiver) are able to give the PALYNZIQ injections, recognize the signs and symptoms of a severe allergic reaction, give an injection of epinephrine, and call for emergency help, if needed
    • Your healthcare provider may recommend that an adult observer (or your caregiver) be with you when you give your PALYNZIQ injection and for at least 1 hour after your injection to watch you for signs and symptoms of a severe allergic reaction and, if needed, give you an injection of epinephrine and call for emergency medical help

    Stop injecting PALYNZIQ and get emergency medical care right away if you have any of the following symptoms:

    • Fainting (passing out)
    • Dizziness or lightheadedness
    • Sudden confusion
    • Trouble breathing or wheezing
    • Chest discomfort or chest tightness
    • Fast heart rate
    • Swelling of your face, lips, eyes, or tongue
    • Throat tightness
    • Flushed skin
    • Skin rash, itching, or raised bumps on skin
    • Nausea, vomiting, or diarrhea
    • Losing control of urine or stools

    Keep the auto-injectable epinephrine with you at all times during treatment with PALYNZIQ. Read the Patient Information that comes with the auto-injectable epinephrine that your healthcare provider prescribes for you for more information.

    If you have a severe allergic reaction, do not continue to take PALYNZIQ until you talk with your healthcare provider. Your healthcare provider will tell you if you can continue treatment with PALYNZIQ.

    People taking PALYNZIQ have also experienced allergic reactions other than anaphylaxis. Talk to your healthcare provider if you experience any allergic reactions when taking PALYNZIQ.

    PALYNZIQ REMS: PALYNZIQ is available only through a restricted program called the PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Talk to your healthcare provider about the PALYNZIQ REMS and how to enroll.

    What should I tell my healthcare provider BEFORE starting PALYNZIQ?
    Tell your healthcare provider about all the medicines you take, including prescription or over-the-counter medicines, vitamins, and herbal supplements.

    Before injecting PALYNZIQ, talk to your healthcare provider right away if you cannot or will not use auto-injectable epinephrine to treat a severe allergic reaction. If you are pregnant or plan to become pregnant while taking PALYNZIQ, talk to your healthcare provider to discuss the risks and benefits of taking PALYNZIQ during pregnancy to you and your unborn baby. If you are breastfeeding or plan to breastfeed, talk to your healthcare provider about the best way to feed your baby if you take PALYNZIQ.

    Before injecting PALYNZIQ, read the Medication Guide and Instructions for Use that come with your PALYNZIQ injection.

    What should I watch for AFTER starting PALYNZIQ?

    PALYNZIQ may cause serious side effects, including:

    • Severe allergic reactions (anaphylaxis)
    • Other allergic reactions to PALYNZIQ can happen during treatment with PALYNZIQ. Contact your healthcare provider right away if you have any of the following symptoms of an allergic reaction including: rash, itching, or swelling of the face, lips, eyes, or tongue. Your healthcare provider may change your dose of PALYNZIQ, stop your treatment with PALYNZIQ for a period of time, or prescribe medicine for you to take before your PALYNZIQ injection to help reduce the symptoms of an allergic reaction

    The most common side effects of PALYNZIQ include injection site reactions (such as redness, itching, pain, bruising, rash, swelling, or tenderness), joint pain, headache, skin reactions that spread and last at least 14 days (such as itching, rash, or redness), itching, nausea, stomach pain, mouth and throat pain, vomiting, cough, diarrhea, feeling very tired, and low levels of Phe in your blood.

    These are not all of the possible side effects of PALYNZIQ. Speak with your healthcare provider right away about any side effects.

    Important notes

    Blood Phe testing and diet

    • Your healthcare provider will monitor your blood Phe concentrations during PALYNZIQ treatment
    • Monitor the amount of protein and Phe that you eat or drink. Your healthcare provider may change the amount of protein and Phe you should have in your diet during treatment with PALYNZIQ, depending on the levels of Phe in your blood. Follow your healthcare provider’s instructions about the amount of protein and Phe you should have in your diet

    Missed dose

    • If a dose is missed, take your next dose as scheduled and do not take two doses of PALYNZIQ to make up for the missed dose

    You may report side effects to BioMarin at 1-877-695-8826 and the FDA by visiting or calling 1-800-FDA-1088.

    Click here to view our Safe Sharps Disposal Policy

    Kuvan Indication

    Kuvan® (sapropterin dihydrochloride) Tablets for Oral Use (100 mg) and Powder for Oral Solution (100 mg and 500 mg) is approved to reduce blood Phe levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Kuvan is to be used with a Phe-restricted diet.

    Kuvan Important Safety Information

    It is not possible to know if Kuvan will work for you without a trial of the medicine. Your doctor will check your blood Phe levels when you start taking Kuvan to see if the medicine is working.

    Starting Kuvan does not eliminate the need for ongoing dietary management. Any change to your diet may impact your blood Phe level. Follow your doctor’s instructions carefully. Your doctor and dietitian will continue to monitor your diet and blood Phe levels throughout your treatment with Kuvan to make sure your blood Phe levels are not too high or too low. If you have a fever, or if you are sick, your Phe level may go up. Tell your doctor and dietitian as soon as possible so they can make any necessary changes to your treatment.

    Children younger than 7 years old treated with Kuvan doses of 20 mg/kg per day are at an increased risk for low levels of blood Phe compared with children 7 years and older. Frequent blood monitoring is recommended in this population to ensure that blood Phe levels do not fall too low.

    Tell your doctor if you have ever had liver or kidney problems, have poor nutrition or have a loss of appetite, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed.
    Kuvan is a prescription medicine and should not be taken by people who are allergic to any of its ingredients. Kuvan and other medicines may interact with each other. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal and dietary supplements.

    If you forget to take your dose of Kuvan, take it as soon as you remember that day. Do not take 2 doses in a day. If you take too much Kuvan, call your doctor for advice.

    The most common side effects reported when using Kuvan are headache, runny nose and nasal congestion, sore throat, diarrhea, vomiting, and cough. Additional adverse reactions reported in connection with worldwide marketing include sore throat, heartburn or pain in the esophagus, inflammation of the lining of the stomach, indigestion, stomach pain, and nausea. These are not all the possible side effects seen with Kuvan. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    Kuvan can cause serious side effects, including:

    • Severe allergic reactions. Stop taking Kuvan and get medical help right away if you develop any of these symptoms of a severe allergic reaction:
      • Wheezing or trouble breathing
      • Nausea
      • Flushing
      • Lightheadedness or fainting
      • Coughing
      • Rash
    • Inflammation of the lining of the stomach (gastritis).Gastritis can happen with Kuvan and may be severe. Call your doctor right away if you have any:
      • Severe upper stomach-area discomfort or pain
      • Blood in your vomit or stool
      • Black, tarry stools
      • Nausea and vomiting
    • Too much or constant activity (hyperactivity) can happen with Kuvan. Tell your doctor if you have any signs of hyperactivity, including fidgeting, moving around or talking too much.

    For more information, call BioMarin Patient and Physician Support (BPPS) at 1-866-906-6100. Please read the full Patient Information by clicking here

    Understanding PKU: What do we know about this rare genetic condition?


    Click here to open the full-size pdf.



    Lysosomal Storage Disorders (MPS I, MPS IVA, MPS VI, CLN2 disease) PKU



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