Elafibranor

Elafibranor (brand name Iqirvo) is an FDA-approved oral medication used to treat primary biliary cholangitis (PBC), a chronic liver disease, in adults. It is taken once daily in combination with ursodiol (ursodeoxycholic acid, UDCA) or alone in patients who cannot tolerate ursodiol.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease in which the bile ducts become progressively damaged, leading to bile buildup, liver inflammation, and, over time, potential liver scarring (cirrhosis). It predominantly affects women over 40.

It is not known if taking elafibranor will improve your chance of survival or prevent liver decompensation.

Elafibranor (Iqirvo) received FDA approval on June 10, 2024, making it the first new treatment for primary biliary cholangitis approved in nearly a decade. It was approved under the accelerated approval pathway based on reductions in alkaline phosphatase levels. Elafibranor is only available under the brand name Iqirvo; there is no generic.

Take elafibranor exactly as your healthcare provider tells you to.

• Take with or without food.
• If you take a bile acid binding resin, take elafibranor at least 4 hours before or 4 hours after you take your bile acid binding resin. If this is not possible, space the time between taking elafibranor and your bile acid binding resin as far apart as possible.

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

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

• Have advanced liver disease
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Your healthcare provider should check for muscle pain or weakness before you start taking elafibranor. Tell your health care provider right away if you have new and/or severe muscle pain or muscle weakness.

It is not known if elafibranor is safe and effective in children under 18 years of age.

Elafibranor is not recommended for use in people with symptoms or signs of advanced liver disease (decompensated cirrhosis), such as confusion; fluid in the stomach area (abdomen); black, tarry, or bloody stools; coughing up or vomiting blood; or vomit that looks like coffee grounds.

Pregnancy

Elafibranor can harm your unborn baby. You should not become pregnant during treatment with this medicine.

Females who can become pregnant:

• You should use an effective method of birth control, such as progestin-only contraceptives containing levonorgestrel or norgestrel, intrauterine systems, or effective non-hormonal contraceptives, during treatment and for 3 weeks after the last dose of elafibranor. Talk to your healthcare provider about birth control methods that may be right for you.
• Tell your healthcare provider right away if you become pregnant or think you may be pregnant.

Pregnancy Safety Study. If you become pregnant while receiving elafibranor, tell your healthcare provider rightaway. There is a pregnancy safety study for women who become pregnant while taking this medicine. Talk to yourhealthcare provider about providing information to the Iqirvo pregnancy safety study.

The purpose of this study is to collect information about your health and your baby’s health. You or your healthcare provider can report your pregnancy by calling 1-844-990-0239 or visiting www.iqirvopregnancyregistry.com

Breastfeeding

It is not known if elafibranor passes into your breast milk. Do not breastfeed while taking elafibranor and for 3 weeks after the last dose. Talk with your healthcare provider about the best way to feed your baby while taking this medicine.

Common Side Effects

The most common side effects of elafibranor are:

• Weight gain
• Diarrhea
• Nausea and vomiting
• Joint stiffness
• Stomach pain
• Constipation
• Muscle pain
• Bone fractures
• Gastroesophageal reflux disease (GERD)
• Dry mouth
• Weight loss
• Rash.

Serious Side Effects and Warnings

Elafibranor may cause the following serious side effects:

• Muscle Problems (Myalgia, Myopathy, Rhabdomyolysis). Treatment with elafibranor may cause muscle pain that can be severe or worsen existing pain and can increase the level of an enzyme in your blood called creatine phosphokinase (CPK); both of which can be signs of muscle damage.

Your healthcare provider should test for muscle weakness or pain before and during treatment. If there is new-onset or worsening muscle pain, your healthcare provider may examine you and order a blood test to check your creatine phosphokinase (CPK) levels. Stop taking elafibranor and call your healthcare provider right away if you have any of the following signs or symptoms:

• Severe muscle pain Unexplained soreness Unexplained muscle weakness Dark, reddish urine.
• Bone Fractures. Taking elafibranor may increase your risk of bone fractures. Tell your healthcare provider about any bone fractures or if you develop pain or have changes in your ability to move around.
• Liver Problems. Elafibranor may cause abnormal liver blood test results. Your healthcare provider should do tests before starting and during treatment to check your liver function. Tell your healthcare provider right away if you have any of the following signs or symptoms of worsening liver problems, during treatment with elafibranor: Swelling of your stomach area (abdomen) from a build-up of fluid Yellowing of your skin or the whites of your eyes Black, tarry, or bloody stools Coughing up or vomiting blood, or your vomit looks like coffee grounds. Mental changes such as confusion, being sleepier than usual or harder to wake up, slurred speech, mood swings, or personality changes.

Tell your healthcare provider right away if you have any of the following symptoms during treatment with elafibranor, and they are severe or do not go away:

• Stomach-area (abdomen) pain Nausea, vomiting, diarrhea Loss of appetite or weight loss New or worsening fatigue Weakness Fever and chills Light-headedness Less frequent urination.
• Allergic reactions. Some people taking elafibranor have had allergic reactions. The reactions happened 2 to 30 days after taking elafibranor. Allergic reaction symptoms may include: Rash Trouble breathing Itching Swelling of your face, lips, tongue, or throat.

If you have any of these symptoms, stop taking elafibranor and call your healthcare provider right away or go to the nearest hospital emergency room.

• Blockage of the bile duct. Taking elafibranor may increase your risk of gallstone development. Call your healthcare provider right away if you develop any signs or symptoms of gallstones, including pain in the upper right stomach area or yellowing of the skin.

Notes:

Your healthcare provider may tell you to stop taking elafibranor temporarily or permanently if there are changes to either your liver tests or the level of an enzyme in your blood related to muscle activity called creatine phosphokinase (CPK).

It is not known if Iqirvo is safe and effective in children under 18 years of age.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Elafibranor works by activating special receptors in cells called PPARs (alpha, delta, and gamma). While scientists don't fully understand exactly how this helps patients with primary biliary cholangitis (PBC), they know it reduces bile acid production in the liver.

This happens through a chain reaction: activating PPAR-alpha and PPAR-delta triggers a protein called FGF21, which then downregulates CYP7A1, the main enzyme responsible for making bile acids from cholesterol. Less bile acid production may help reduce liver damage in PBC.

Elafibranor belongs to the drug class called peroxisome proliferator-activated receptor (PPAR) agonists.

Elafibranor (Iqirvo) was approved based on positive results from the ELATIVE clinical trial (NCT04526665), which reported that 51% of patients achieved biochemical response (reduced ALP to <1.67x upper normal limit, decreased by ≥15%, with normal bilirubin) versus 4% on ursodiol alone.

Benefits included reduced alkaline phosphatase levels (sustained from week 4), improved lipid profiles, and decreased itching. However, survival benefits haven't been proven, and continued approval depends on a clinical benefit being shown in confirmatory trials.

Adult Dose of Elafibranor for PBC

• 80 mg orally once daily.

Tell your healthcare provider about all medications you take, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take:

• Hormonal Contraceptives (Birth Control Pills): Elafibranor may reduce the effectiveness of hormonal birth control. Switch to non-hormonal contraceptives OR add a barrier method. Continue these precautions for 3 weeks after stopping this medicine
• Statins (HMG-CoA Reductase Inhibitors): These may increase your risk of muscle injury when combined with elafibranor. Examples include atorvastatin (Lipitor), pravastatin, rosuvastatin (Crestor), and simvastatin. Your doctor will monitor closely for muscle pain, weakness, and CPK levels
• Other PPAR Agonists: Taking elafibranor with other PPAR-alpha agonists (such as fenofibrate) or PPAR-gamma agonists (such as pioglitazone or rosiglitazone) may increase your risk of muscle or liver injury. Your doctor will monitor you closely for signs of muscle or liver problems if you take these medicines together.
• Rifampin: Your doctor will monitor your liver function (ALP, bilirubin) if you start rifampin during treatment
• Bile Acid Sequestrants: These may reduce the absorption of elafibranor. Examples include cholestyramine and colestipol. Take elafibranor 4 hours before or 4 hours after these medications

This is not a complete list, and other interactions may occur. See the Iqirvo (elafibranor) Package Insert for more information.

The cost of Iqirvo depends on your insurance plan. There is currently no generic elafibranor available. Eligible patients may pay as little as $0 per prescription through the Ipsen Cares patient support program.

To check eligibility:

• Contact Ipsen Cares at the phone number on the official Iqirvo website
• Visit www.iqirvo.com/support-and-resources
• Speak with your healthcare provider or pharmacist

For more information, see Iqirvo Prices, Coupons, Copay Cards & Patient Assistance.

Store elafibranor tablets at room temperature between 59°F and 86°F (15°C and 30°C)

Store in the original package (bottle and carton) to protect from moisture and light

Keep out of reach of children.

Elafibranor is only available as the brand Iqirvo.

Active ingredient: elafibranor

Inactive ingredients: colloidal silica dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and povidone.

Film coating: iron oxide red, iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.

Available as 80 mg tablets.

Elafibranor is manufactured for Ipsen Biopharmaceuticals, Inc., One Main Street, 7th Floor, Cambridge, MA, 02142, USA.