If you or a loved one has phenylketonuria, you may be considering treatment options. One medicine you might hear about is Palynziq (pegvaliase-pqpz).
Phenylketonuria, or PKU for short, is a rare condition you are born with. It affects how your body uses an amino acid called phenylalanine (Phe). Phe is one of the building blocks of protein. It’s found in many foods, especially high-protein ones like meat, eggs, and milk, and in the sweetener aspartame.
If you have PKU, your body does not make the enzyme needed to break down Phe. As a result, Phe builds up in your blood and can be harmful.
The main treatment for PKU is a low-protein diet to keep Phe levels safe. Some medicines can also help. Palynziq is an injectable medicine that can lower Phe levels. It’s usually only prescribed when diet or other treatments aren’t helping enough to manage Phe levels.
Palynziq may also be used for other conditions as determined by your health care provider. Below are common questions and answers about Palynziq for phenylketonuria.
Is Palynziq Right for Me?
To decide if Palynziq is right for you, your health care provider will consider your current treatment plan and your blood levels of phenylalanine (Phe). Palynziq is FDA-approved to treat adults with phenylketonuria (PKU) who have high blood levels of Phe above 600 micromoles per liter (abbreviated micromol/L or µmol/L) despite following their usual treatment plan for PKU. Your doctor may refer to Phe levels in units of milligrams per deciliter (mg/dL). Note that 600 µmol/L is equal to 10 mg/dL.
Also, you and your health care provider will discuss the possible risks and benefits to decide if Palynziq is right for you. One of the most important risks to consider is the possibility of serious allergic reactions (anaphylaxis). These reactions could happen at any time during treatment.
To use Palynziq, you must be willing to carry auto-injectable epinephrine (such as an EpiPen) with you at all times in case of an allergic reaction. You or your caregiver will be shown how and when to use epinephrine. Because of this risk, Palynziq is available only through a special safety program. Before starting treatment, you must enroll in this program and understand the possible risks.
Palynziq is only approved for use in adults. It isn’t known if this medicine is safe or effective for treating PKU in babies or children.
How Does Palynziq Work for Phenylketonuria?
Phenylketonuria (PKU) is a genetic condition where your body does not make an enzyme needed to break down phenylalanine (Phe), an amino acid found in foods. As a result, Phe can build up to harmful levels in your blood and brain.
Palynziq helps your body break down Phe by providing a “substitute” enzyme (pegvaliase) to replace the one your body cannot make. This enzyme changes Phe into natural substances that your body is able to use. Thus, Palynziq lowers Phe levels in your blood.
The “substitute” enzyme in Palynziq is made with the help of bacteria in a lab. The bacteria are specially designed to make the enzyme, which is then purified to remove all bacteria.
How Is Palynziq Used, and What Should I Expect During Treatment?
Palynziq comes in a prefilled syringe and is given as an injection under the skin (subcutaneous). A health care professional will give you your first dose and may teach you or a caregiver how to inject it safely at home. You can inject Palynziq into the front of your thighs or your abdomen (belly area), at least 2 inches away from your belly button. If a caregiver gives the injection, the upper arms or top of the buttocks may also be used.
You will start with a low dose that increases slowly over time. This gradual increase helps your body adjust to the medicine and lowers the chance of side effects. Here is an example of a typical dosing schedule for Palynziq:
- Weeks 1 to 4: 2.5 mg once weekly
- Week 5: 2.5 mg twice weekly
- Week 6: 10 mg once weekly
- Week 7: 10 mg twice weekly
- Week 8: 10 mg four times per week
- Week 9: 10 mg once daily
- Week 10 and on (maintenance): 20 mg to 60 mg once daily
The maintenance dose depends on your Phe levels. If your Phe levels remain high on 20 mg daily, your health care provider may increase your dose to 40 mg once daily for at least 16 weeks. If your Phe levels are still high, your dose may be raised to a maximum of 60 mg once daily for at least 16 weeks. If there is not enough improvement on the highest dose, your provider may stop Palynziq and recommend other options.
Throughout treatment, your provider may adjust your dose or diet to help keep your Phe levels in a healthy range. Most PKU experts recommend keeping Phe levels between 120 and 360 µmol/L. Talk with your prescriber about the right target or range for you.
To help lower the risk of allergic reactions, your provider may recommend that you take certain medicines before each dose. For home injections, it’s best to have a caregiver or another adult stay with you for at least an hour afterward. This person should know how to recognize signs of a serious allergic reaction, use an epinephrine auto-injector, and call for emergency help, if needed.
Each Palynziq prefilled syringe is used for only one injection. Always follow your provider’s exact instructions and review the Instructions for Use before each dose.
How Was Palynziq Studied for Phenylketonuria, and What Were the Main Results?
Two studies were done to test Palynziq in adults with phenylketonuria (PKU) whose blood phenylalanine (Phe) levels stayed high even with diet changes or other treatments. The two studies were called PRISM-1 and PRISM-2.
The PRISM-1 study looked at how well people tolerated Palynziq and how long it took people to reach the highest dose they could safely take (called a maintenance or target dose).
The PRISM-1 study included 261 adults with PKU. The average age was 29 years. Most participants were White; about half were female and half were male. Most people had uncontrolled Phe levels (above 600 µmol/L) despite following their usual treatment plan. Before joining the study, people may have managed their PKU with diet changes and/or a medicine called sapropterin. But anyone taking sapropterin had to stop it at least two weeks before starting Palynziq.
People were randomly assigned to reach a daily target dose of either 20 mg or 40 mg of Palynziq. Everyone started with a low dose and increased slowly, based on how well they tolerated the medicine. Most people (about 75%) were able to reach their target dose of 20 mg or 40 mg. For people who reached their target dose, the median time was 10 weeks (range: nine to 29 weeks) in the 20 mg group and 11 weeks (range: 10 to 33 weeks) in the 40 mg group. During the study, 21% of people stopped using Palynziq. Most people moved onto the next study, PRISM-2.
The PRISM-2 study included 164 adults who were already using Palynziq. Everyone kept taking Palynziq for up to 13 weeks. Only people who had a response could qualify for the next part of the study. A response meant their blood Phe levels needed to drop by at least 20%, compared to before they started Palynziq. Out of 164 people, about half (86 people) had a response and continued to the next part of the study.
In the next part of the study, researchers compared the effects of staying on Palynziq versus stopping it. The people in the study were randomly assigned to either keep using Palynziq or switch to a placebo (a shot with no active medicine) for eight weeks. No one knew which one they were getting. This part of the study was called the randomized withdrawal period.
The table below shows the average Phe levels (µmol/L) at different time points before and during the study.
| Treatment group | Phe level at pre-treatment baseline | Phe level right before the randomized withdrawal period | Phe level at week 8 of the randomized withdrawal period |
| Palynziq 20 mg once daily | 1,450 | 597 | 553 |
| Placebo 20 mg once daily | 1,459 | 564 | 1,509 |
| Palynziq 40 mg once daily | 1,186 | 411 | 566 |
| Placebo 40 mg once daily | 1,109 | 508 | 1,164 |
People who continued using either dose of Palynziq generally maintained lower Phe levels, while those switched to a placebo in the randomized withdrawal period saw their Phe levels return to where they were before their first study involvement.
Can Palynziq Be Used Long Term, and Does It Keep Working?
Yes, Palynziq can be an effective long-term treatment for some people. The PRISM study continued to see how well it worked over time. Many people in the study were able to continue using Palynziq long term to manage their PKU. Of the 261 adults who joined the first PRISM study, 101 (39%) stopped Palynziq, and the rest stayed on treatment. About 64% were treated with Palynziq for at least two years. And about 56% were treated for at least three years.
Among the 118 adults who reached a target dose of 20 mg in the first part of the study), 77 people stayed on Palynziq for at least three years.
As the study continued, Palynziq worked for many people to bring down their high Phe levels. For example, among the 118 people described above, 91 people (77%) had a response (a Phe level of 600 µmol/L or lower) within three years. (Note that some people’s Phe levels could have fluctuated over time, but here, the researchers only counted a response as the first time someone’s level dropped to that range.)
Most experts recommend that adults with PKU should maintain Phe levels between 120 and 360 µmol/L. In studies, many people using Palynziq maintained Phe levels within this recommended range:
- Among 86 people who used Palynziq for more than two years, 66% had a Phe level of 360 µmol/L or lower at the two-year point.
- Among 77 people who used Palynziq for more than three years, 66% had a Phe level of 360 µmol/L or lower at the three-year point.
Some people maintained Phe levels that were even lower than the recommended range.
Overall, these results suggest that Palynziq is an effective medicine to reduce Phe levels and maintain them over time in adults with PKU. Keep in mind that your results may vary from those seen in studies.
How Do I Know if Palynziq Is Working, and How Fast Does It Start to Work?
Palynziq does not work right away. Your health care provider will check your blood phenylalanine (Phe) levels regularly to see how well Palynziq is working. This medicine must be started at a low dose then slowly increased over time. So it could take several months or longer to see if the medicine will bring your Phe levels down. Your provider may adjust your dose or diet based on your blood test results to help keep your Phe levels in a safe range.
Is There Any Cost Assistance Available?
A cost assistance program is available from BioMarin, the maker of Palynziq. It may reduce the amount you pay. Whether you qualify to enroll may depend on what type of insurance you have or if you are uninsured. Visit www.biomarin-rareconnections.com from the drugmaker for more information about Palynziq costs and copay savings.
You can also contact the drugmaker at 866-906-6100 to connect with a representative for financial support information and other resources.
