Sephience
Pronunciation: seh-FIGH-ence
Generic name: sepiapterin
Dosage form: oral powder for reconstitution
What is Sephience?
Sephience is a prescription medication used to treat phenylketonuria (PKU) to help reduce elevated levels of phenylalanine in the blood. Sephience works by activating phenylalanine hydroxylase (PAH), the enzyme that breaks down phenylalanine. People with PKU lack sufficient PAH, leading to a harmful buildup of phenylalanine.
Sephience is FDA approved for the treatment of hyperphenylalaninemia (HPA) in both adults and children aged one month and older who have sepiapterin-responsive PKU. It should be used with a phenylalanine-restricted diet.
This medication is available as an oral powder that is mixed with water or apple juice and taken once daily with food.
How effective is Sephience?
In the APHENITY clinical trial (NCT05099640), patients treated with Sephience experienced a 63% reduction in blood phenylalanine levels after six weeks, compared to just a 1% reduction in those receiving a placebo. Sephience received FDA approval on July 28, 2025, following these positive results from the Phase 3 APHENITY trial and its long-term extension study.
How does it work?
The active ingredient in Sephience is sepiapterin, a PAH activator with a dual mechanism of action. Once ingested, sepiapterin is quickly converted into tetrahydrobiopterin. This compound activates the PAH enzyme and also prevents it from misfolding, improving its function and enhancing the breakdown of phenylalanine.
What is Phenylketonuria?
Phenylketonuria is caused by a genetic mutation that impairs the production of PAH, the enzyme needed to process phenylalanine. Without this enzyme, phenylalanine accumulates to toxic levels and can damage the brain.
Sephience side effects
The most common Sephience side effects are diarrhea, headache, abdominal pain, hypophenylalaninemia, yellow or orange stool (feces), and throat pain. These side effects occurred in 2% or more of patients and were greater than placebo.)
Serious Sephience side effects include:
- Increased your risk of bleeding. Tell your healthcare provider if you develop any symptoms of bleeding, including:
- bruising or red or purple skin marks
- bleeding longer than usual or that does not stop
- menstrual bleeding that is heavier than normal
- low blood phenylalanine (hypophenylalaninemia). Low blood phenylalanine levels are common during treatment with this medicine and can be severe.
This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088
Related/similar drugs
Before taking or giving this medicine
Tell your healthcare provider about all of your medical conditions, including if you:
- are pregnant or plan to become pregnant, as it is not known if Sephience will harm your unborn baby.
- are breastfeeding or plan to breastfeed, as it is not known if Sephience passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take this medicine.
How should I take or give Sephience?
Take or give Sephience exactly as your healthcare provider tells you.
Your healthcare provider will tell you how much to take or give.
Take or give Sephience 1 time each day with food. You must take or give more food after the dose.
Your healthcare provider may change your or your child’s dose depending on your weight and age.
Sephience comes as a packet containing oral powder.
- For doses less than 1,000 mg: mix Sephience oral powder with water or apple juice before taking or giving.
- For doses 1,000 mg or greater: Sephience oral powder can be mixed with water, apple juice, strawberry jam, or applesauce before taking or giving.
- See the detailed Instructions for Use that comes with Sephience for information about the correct way to prepare, take, or give a dose of oral powder.
During treatment with this medicine, you or your child will have regular check-ups with your healthcare provider.
Your healthcare provider will do blood tests before and during your treatment with this medicine to check your blood phenylalanine levels.
Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with this medicine if you have certain side effects.
Your healthcare provider may change your diet during treatment. Follow your healthcare provider’s instructions and do not make any changes to your diet without first talking to your healthcare provider.
What happens if I miss a dose?
If you or your child misses a dose of this medicine, take or give it as soon as possible. Do not take 2 doses in a day. Continue with your normal dosing schedule the following day.
Interactions
Tell your healthcare provider about all medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Sephience and other medicines may affect each other, causing side effects. Sephience may affect the way other medicines work, and other medicines may affect how Sephience works. Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist when you get a new medicine.
Especially tell your healthcare provider if you take:
- a medicine that contains levodopa
- an antifolate medicine
- other medicines are also used to lower phenylalanine
- medicines used to treat erectile dysfunction (phosphodiesterase 5 inhibitors or PDE5)
Not all possible interactions are listed in this medication guide.
Ingredients
Active ingredients: sepiapterin
Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, isomalt, magnesium stearate, mannitol, microcrystalline cellulose, sucralose, and xanthan gum.
Storage
Store oral powder packets at room temperature between 68°F to 77°F (20°C to 25°C).
For Sephience oral powder that is mixed with water, apple juice, strawberry jam, or applesauce:
- If the mixture is not taken or given right away, cover and store the mixture at room temperature between 68°F to 77°F (20°C to 25°C) for up to 6 hours or refrigerate between 36°F to 46°F (2°C to 8°C) for no more than 24 hours.
- If the stored mixture was prepared with water or apple juice, stir the mixture for 30 seconds or more before taking or giving the dose.
- If the stored mixture was prepared with strawberry jam or applesauce, stir the mixture for 60 seconds or more before taking or giving the dose.
- Throw away (discard) unused mixture after 6 hours at room temperature or after 24 hours if refrigerated. Keep Sephience and all medicines out of the reach of children.
Keep Sephience and all medicines out of the reach of children.
Company
Manufactured by: Allphamed PHARBIL Arzneimittel GmbH Hildebrand str. 12, 37081 Gottingen, Germany (DEU)
Manufactured for: PTC Therapeutics, Inc., Warren, NJ 07059
References
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.