Palynziq (pegvaliase-pqpz)

Palynziq (pegvaliase-pqpz) is a prescription medicine used to lower blood levels of phenylalanine in adults with PKU (phenylketonuria) who have uncontrolled blood phenylalanine levels above 600 micromol/L (10 mg/dL) on their current treatment.

It is not known if Palynziq is safe and effective in children.

Palynziq is only available through a restricted program called the Palynziq Risk Evaluation and Mitigation Strategy (REMS) Program. Before you can receive Palynziq, you must:

• enroll in this program.
• receive education about the risk of a severe allergic reaction (anaphylaxis) by a healthcare provider certified in the Palynziq REMS to be sure that you understand the risks and benefits of treatment with Palynziq.
• fill the prescription your healthcare provider gives you for the auto-injectable epinephrine and carry it with you at all times during treatment with Palynziq.
• carry the Palynziq Patient Wallet Card with you at all times.

Talk to your healthcare provider for more information about the Palynziq REMS and how to enroll.

WARNING

Palynziq can cause a severe allergic reaction (anaphylaxis) that may be life-threatening and can happen any timeduring 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.
• If you have a severe allergic reaction during treatment with Palynziq, you will need to receive an auto-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 medical 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 of a severe allergic reaction during treatment with Palynziq:

• 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
• Your healthcare provider will prescribe an 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. 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. Tell your healthcare provider that you had a severe allergic reaction. Your healthcare provider will tell you if you can continue treatment with Palynziq.
  • Your healthcare provider may prescribe other medicines to take before your Palynziq injection that may help reduce the symptoms of an allergic reaction.
  • If your healthcare provider decides that you can continue treatment with Palynziq after a severe allergic reaction, you will receive your next 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 give you a Palynziq Patient Wallet Card that describes symptoms that you (or your caregiver), or your observer, should know that require you to get emergency medical care right away. Carry this card with you at all times during treatment with Palynziq. It is important to show your Palynziq Patient Wallet Card to any other healthcare provider who treats you.

Palynziq may cause serious side effects, including:

• 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 or 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, tenderness
• joint pain
• headache
• skin reactions that spread on your skin and last at least 14 days, such as itching, rash, redness
• itching
• nausea
• stomach pain
• mouth and throat pain
• vomiting
• cough
• diarrhea
• feel very tired
• low levels of phenylalanine in your blood

These are not all the possible side effects of Palynziq. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• Your healthcare provider will give you the Palynziq injection until they decide that you (or your caregiver) can give it.
• Your healthcare provider may prescribe medicine for you to take before your Palynziq injection to help reduce the symptoms of an allergic reaction.
• If your healthcare provider decides that you (or your caregiver) can give your Palynziq injections, you (or your caregiver) will be shown how to prepare and give your Palynziq injections. See the “Instructions for Use” for detailed instructions on how to prepare and give an injection of Palynziq.
• Use Palynziq exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much Palynziq to inject and when to inject it.
• Palynziq comes in prefilled syringes with 3 different strengths (2.5 mg, 10 mg, or 20 mg). You may need more than 1 Palynziq prefilled syringe for your prescribed dose.
• Monitor the amount of protein and phenylalanine that you eat or drink. Your healthcare provider may change the amount of protein and phenylalanine you should have in your diet during treatment with Palynziq, depending on the levels of phenylalanine in your blood. Follow your healthcare provider's instructions about the amount of protein and phenylalanine you should have in your diet.
• If you miss a dose, take your next dose at the regular time. Do not take two doses of Palynziq to make up for a missed dose.

Effect Of Palynziq On Other PEGylated Products

In a single dose study of Palynziq in adult patients with PKU, two patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced hypersensitivity reactions. One of the two patients experienced a hypersensitivity reaction on day 15 after a single Palynziq dosage of 0.67 mg within 15 minutes following medroxyprogesterone acetate injectable suspension, and subsequently experienced anaphylaxis on day 89 within 30 minutes after the next dose of medroxyprogesterone acetate injectable suspension. The other patient experienced a hypersensitivity reaction on day 40 after a single Palynziq dosage of 0.08 mg within 10 minutes following medroxyprogesterone acetate injectable suspension. Both patients had high anti-PEG IgG antibody titers at or around the time of the hypersensitivity reactions.

In Palynziq clinical trials, the majority of patients developed anti-PEG IgM and IgG antibodies after treatment with Palynziq. The clinical effects of concomitant treatment with different PEGylated products is unknown. Monitor patients treated with Palynziq and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis.

Before injecting Palynziq, tell your healthcare provider about all of your medical conditions, including if you:

• are pregnant or plan to become pregnant. Palynziq may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you might be pregnant while taking Palynziq.
  • If your phenylalanine levels are too high or too low during pregnancy, this may also affect your unborn baby. You and your healthcare provider can decide the best way for you to manage your blood phenylalanine levels and discuss the risks and benefits of taking Palynziq during pregnancy to you and your unborn baby. It is very important to keep your phenylalanine levels at the levels your healthcare provider recommends during pregnancy.
  • Pregnancy Surveillance Program. There is a pregnancy surveillance program for females who take Palynziq during pregnancy, or who become pregnant while receiving Palynziq or within 1 month after their last dose of Palynziq. The purpose of this program is to collect information about the health of you and your baby while taking Palynziq. Talk to your healthcare provider about how you can take part in this program or call BioMarin at 1-866-906-6100.
• are breastfeeding or plan to breastfeed. It is not known if Palynziq passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Palynziq.