Seladelpar

Seladelpar is used to treat primary biliary cholangitis (PBC) in adults. It is an oral capsule taken once a day in combination with ursodeoxycholic acid (UDCA) in adults who have not responded well to UDCA, or used alone in those unable to tolerate UDCA.

Seladelpar is not used in people with advanced liver disease (decompensated cirrhosis).

Key Facts About Seladelpar (Livdelzi)

• Generic name: Seladelpar lysine
• Brand name: Livdelzi
• Drug class: PPAR-delta agonist
• FDA approved: August 14, 2024 (accelerated approval)
• Used for: Primary biliary cholangitis (PBC) in adults
• Dosage: 10 mg capsule once daily
• Manufacturer: Gilead Sciences
• Generic available: No

Mechanism of Action

Seladelpar belongs to the drug class called peroxisome proliferator-activated receptor (PPAR)-delta agonists and works through multiple pathways:

• Activates PPAR-delta receptors that control metabolic and liver disease pathways
• Reduces bile acid synthesis and production
• Decreases inflammation in the liver
• Reduces fibrosis (scarring) progression
• Improves lipid metabolism and transport

Clinical benefit: By reducing bile acid production, seladelpar helps counteract liver damage caused by bile acid buildup in PBC patients, although it is unknown if it improves survival or prevents liver decompensation.

Clinical Trial Results

Approval of seladelpar was based on the results of the Phase 3 RESPONSE trial (NCT04620733), which reported:

• 62% of patients achieved composite biochemical response (vs 20% placebo)
• 25% normalized ALP levels (vs 0% placebo)
• Statistically significant reduction in pruritus (itching) compared to placebo.

Standard Seladelpar Dosage

• Adult dose: 10 mg (1 capsule) once daily
• Timing: Can be taken with or without food
• Consistency: Take at the same time each day
• Duration: Long-term treatment as directed by a physician.

Important Timing with Other Medications

Bile acid-binding resins (cholestyramine, colestipol):

• Take seladelpar at least 4 hours before or 4 hours after bile acid-binding resins
• If 4-hour separation is not possible, space as far apart as possible
• This prevents absorption interference.

Absolute Contraindications

Do not use seladelpar in:

• Advanced liver disease (decompensated cirrhosis)
• Children or adolescents (safety not established)
• Patients with biliary obstruction
• Severe hepatic impairment.

Signs of advanced liver disease include:

• Mental confusion or altered consciousness
• Fluid accumulation in the abdomen (ascites)
• Black, tarry, or bloody stools
• Vomiting blood or coffee-ground material
• Severe jaundice.

Tell Your Healthcare Provider if You Have:

• Liver disease.
• A blockage of the bile ducts in your liver (biliary obstruction)
• Pregnancy or breastfeeding plans.

Pregnancy and Breastfeeding Considerations

Pregnancy: It is not known if seladelpar will harm an unborn baby. If you become pregnant while taking seladelpar, tell your healthcare provider right away.

Pregnancy Safety Study. Talk to your healthcare provider about providing information about the Livdelzi (seladelpar) pregnancy safety study. The purpose of this pregnancy safety study is to capture information about your health and your baby’s health. You or your healthcare provider can report your pregnancy by calling 1-800-445-3235.

Breastfeeding: It is not known if seladelpar passes into your breast milk. Talk with your healthcare provider about the best way to feed your baby if you take seladelpar.

Common side effects

The most common side effects of seladelpar are:

• Headache
• Stomach (abdominal) pain
• Nausea
• Abdominal swelling (distension)
• Dizziness.

Serious side effects and warnings

Bone Fractures

Seladelpar may increase your risk of bone fractures.

• Monitor for bone pain or mobility changes
• Discuss bone health monitoring with your healthcare provider
• Consider calcium and vitamin D supplementation.

Liver Function Changes

Increased liver enzymes in the blood have occurred when taking more seladelpar than prescribed. Your healthcare provider will do tests to check your liver before you start and during treatment with seladelpar. Tell your healthcare provider right away if you have any of the following signs or symptoms of worsening liver problems during treatment with seladelpar:

• Swelling of your stomach area (abdomen) from a build-up of fluid
• Yellowing of your skin or the whites of your eyes
• Mental changes such as confusion, being sleepier than usual, or harder waking up from sleep
• Pain on the right side of your stomach, slurred speech, mood swings, or changes (abdomen) in personality
• Black, tarry, or bloody stools
• Coughing up or vomiting blood, or your vomit looks like “coffee grounds”.

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

Tell your healthcare provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of seladelpar. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

If you take too much seladelpar, call your healthcare provider or get emergency medical help right away.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Seladelpar can affect the way certain medicines work. Certain other medicines may affect the way this medicine works.

Major Drug Interactions to Avoid

Strong CYP2C9 Inhibitors (avoid combination):

• Cotrimoxazole (Bactrim)
• Fluoxetine (Prozac)
• Amiodarone.

OAT3 Inhibitors (avoid or monitor closely):

• Probenecid
• Rifampin (monitor ALP and bilirubin)
• Cabotegravir

Monitor Closely With These Medications

Dual CYP2C9/CYP3A4 Inhibitors:

• Fluconazole - monitor for increased side effects

BCRP Inhibitors:

• Rosuvastatin (Crestor)
• Glyburide
• Nitrofurantoin
• Cimetidine

CYP2C9 Poor Metabolizers:

• May need more frequent monitoring with CYP3A4 inhibitors

Bile Acid Binding Resins

Seladelpar should be taken at least 4 hours before or 4 hours after you take medicines to help lower your cholesterol, called bile acid-binding resins (examples include cholestyramine or colestipol). If this is not possible, space the time between taking seladelpar and your bile acid-binding resin as far apart as possible.

This is not a complete list of interactions. See the Livdelzi (seladelpar) Package Insert for a full list.

Store capsules at room temperature between 68°F to 77°F (20°C to 25°C).

Keep out of the reach of children.

Seladelpar is only available under the brand name Livdelzi. There is no generic.

Active ingredient: seladelpar lysine

Inactive ingredients (Livdelzi): butylated hydroxytoluene, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, and hard gelatin shells.

Capsule shells contain gelatin, titanium dioxide, black iron oxide, yellow iron oxide, red iron oxide, and the colorant FD&C Blue #2.

Seladelpar is available as a 10 mg capsule.

Seladelpar is manufactured by Gilead Sciences, Inc., under the brand Livdelzi. Gilead Sciences' headquarters are in Foster City, California.