Livdelzi

Livdelzi (seladelpar) is used to treat primary biliary cholangitis (PBC) in adults. Livdelzi is:

• taken together with ursodeoxycholic acid (UDCA) in adults who have not responded well enough to UDCA alone, or
• used on its own in adults who cannot tolerate UDCA.

Primary biliary cholangitis is a long-term autoimmune disease in which the small bile ducts in the liver become damaged. Bile then builds up in the liver, which can cause inflammation, scarring (fibrosis), and symptoms such as fatigue and itching (pruritus). Over time, untreated PBC can lead to cirrhosis and liver failure.

Livdelzi is a PPAR-delta (peroxisome proliferator-activated receptor delta) agonist. It works mainly by lowering the amount of bile acid the liver makes, which helps reduce the bile acid buildup that damages the liver in PBC. The full way it works in PBC is not completely understood.

Doctors measure how well Livdelzi is working using a liver blood test called alkaline phosphatase (ALP). Livdelzi was approved by the FDA on August 14, 2024, under accelerated approval based on its ability to lower ALP. It is not yet known whether Livdelzi improves survival or prevents liver decompensation, and continued approval may depend on confirming its benefit in further trials.

Livdelzi was studied in a 12-month, randomized, double-blind, placebo-controlled trial (the RESPONSE trial, NCT04620733) in 193 adults with PBC who had an inadequate response to, or could not tolerate, UDCA. Most patients (94%) took Livdelzi together with UDCA, and the rest took it alone.

After 12 months:

• 62% of people taking Livdelzi had a biochemical response (a set improvement in ALP and bilirubin), compared with 20% of those taking placebo.
• 25% of people taking Livdelzi had their ALP return to normal, compared with 0% on placebo.
• Among people who started with moderate to severe itching, those taking Livdelzi had a greater reduction in itch (pruritus) than those on placebo.

These results show Livdelzi improves liver blood tests and can ease itching. They do not yet show whether it helps people live longer or prevents liver complications.

Longer-term results from an open-label extension study (ASSURE), reported at medical meetings in 2025 and 2026, suggest these improvements in liver blood tests are maintained for up to 2 years. These data are not yet part of the FDA-approved label.

Take Livdelzi exactly as your healthcare provider tells you to. Do not take more than prescribed.

• Take Livdelzi by mouth 1 time each day.
• Livdelzi may be taken with or without food.
• If you also take a cholesterol-lowering medicine called a bile acid-binding resin (for example, cholestyramine or colestipol), take Livdelzi at least 4 hours before or 4 hours after the resin. If that is not possible, space the two as far apart as you can.

Livdelzi is not recommended for people who have advanced liver disease (decompensated cirrhosis). Signs of advanced liver disease may include:

• confusion
• fluid in the stomach area (abdomen)
• black, tarry, or bloody stools
• coughing up or vomiting blood, or vomit that looks like "coffee grounds"

Before taking Livdelzi, tell your healthcare provider about all your medical conditions, including if you:

• have advanced liver disease
• think you may have a blockage of the bile ducts in your liver (biliary obstruction)
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

It is not known if Livdelzi will harm an unborn baby. If you become pregnant while taking Livdelzi, tell your healthcare provider right away. There is a pregnancy safety study for women who take Livdelzi during pregnancy, which collects information about your health and your baby's health. You or your healthcare provider can report a pregnancy by calling 1-800-445-3235.

Breastfeeding

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

The most common side effects of Livdelzi are:

• headache
• stomach (abdominal) pain
• nausea
• abdominal swelling (distension)
• dizziness

Less common side effects reported more often than with placebo included indigestion (dyspepsia), rash, hair loss (alopecia), anemia, and cough. In the clinical trial, some people also had a drop in a kidney function test (eGFR); this generally stabilized or improved while treatment continued and did not require stopping Livdelzi.

Serious side effects and warnings

Livdelzi can cause the following serious side effects.

Bone fractures. Fractures occurred in about 4% of people taking Livdelzi in the clinical trial, and in none of those taking placebo. Your healthcare provider may monitor your bone health during treatment. Tell your healthcare provider about any bone fractures, new pain, or changes in your ability to move around.

Changes in liver tests. Higher liver enzyme levels in the blood have happened, mainly at doses higher than prescribed. Your healthcare provider will check your liver with blood tests before you start Livdelzi and during treatment, and may pause or stop it if your liver tests worsen. Tell your healthcare provider right away if you have any of these signs or symptoms of worsening liver problems:

• 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 to wake up, slurred speech, mood swings, or changes in personality
• pain on the right side of your stomach area (abdomen)
• black, tarry, or bloody stools
• coughing up or vomiting blood, or vomit that looks like "coffee grounds"

Bile duct blockage (biliary obstruction). Livdelzi should be avoided if you have a complete blockage of the bile ducts. If a blockage is suspected, your healthcare provider may stop Livdelzi while you are evaluated. Tell your healthcare provider right away about pain in the upper right side of your abdomen or yellowing of the skin or eyes.

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

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

Usual adult dosage of Livdelzi for PBC

• Livdelzi 10 mg once daily.
• Take with or without food.

No dosage change is needed for mild liver impairment or for kidney impairment. Livdelzi has not been studied in people on dialysis, and it is not recommended in people with decompensated cirrhosis.

If you take too much Livdelzi, call your healthcare provider or get emergency medical help right away. There is no specific antidote; treatment focuses on supportive care. Because Livdelzi is highly bound to proteins in the blood, dialysis is not expected to help remove it.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines can change how Livdelzi works. In particular, tell your healthcare provider if you take:

• probenecid (used for gout). This should be avoided with Livdelzi.
• a strong CYP2C9 inhibitor. Your provider will watch you more closely for side effects.
• a medicine that is both a moderate CYP2C9 and a moderate or strong CYP3A4 inhibitor, such as fluconazole. Your provider will watch you more closely for side effects.
• a medicine that blocks several drug transporters (OATP1B1, OATP1B3, and BCRP) at once, such as cyclosporine. Your provider will watch you more closely for side effects.
• rifampin. It can reduce the effect of Livdelzi, so your provider may monitor your ALP and bilirubin.
• a bile acid-binding resin (such as cholestyramine or colestipol). Take Livdelzi at least 4 hours before or after it.

People who are CYP2C9 poor metabolizers may need closer monitoring if they also take a moderate to strong CYP3A4 inhibitor. This is not a complete list of interactions. See the Livdelzi prescribing information for the full list.

Store Livdelzi at room temperature, 68°F to 77°F (20°C to 25°C). Keep Livdelzi in its original container to protect it from light. Keep out of the reach of children.

Active ingredient: seladelpar lysine

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

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

Livdelzi is available as 10 mg capsules.