Hepcludex

Hepcludex is used to treat chronic (long-lasting) hepatitis delta virus (HDV) infection in adults without cirrhosis or with compensated cirrhosis. Hepcludex injection is given subcutaneously once a day.

Chronic HDV is a serious liver disease that occurs only as a co-infection in individuals with chronic hepatitis B virus (HBV) and is associated with rapid disease progression, liver failure, and an increased risk of death. Hepcludex works by blocking the entry of both HDV and HBV into liver cells, and is the first FDA-approved anti-viral treatment for this disease.

Hepcludex (bulevirtide-gmod) received FDA accelerated approval on May 22, 2026, based on data from the Phase 3 MYR301 clinical trial (NCT03852719) showing reductions in HDV RNA and ALT normalization. Continued approval may be contigent on a clinical benefit being shown in future trials.

See the Instructions for Use in the Hepcludex Prescribing Information for instructions on how to prepare and inject your prescribed dose of Hepcludex. Use Hepcludex exactly as your healthcare provider tells you to take it. Do not change your dose unless your healthcare provider tells you to.

Hepcludex is given as an injection under your skin (subcutaneous) by you or a caregiver.

• Your healthcare provider should show you or your caregiver how to prepare and inject Hepcludex before you use it for the first time.
• Administer Hepcludex 1 time each day.

Inject into the lower abdomen or upper thighs. If someone else is injecting, the back of the upper arms is also an option.

• Rotate injection sites daily
• Avoid moles, scars, bruises, tattoos, or irritated/broken skin
• Avoid the area within 1 inch of the belly button.

Do not change your dose or stop taking Hepcludex without first talking with your healthcare provider. Stay under a healthcare provider's care when taking Hepcludex.

Do not miss a dose of Hepcludex.

When your Hepcludex supply starts to run low, get more from your healthcare provider or pharmacy. This is very important because your HDV and HBV infection may get worse (flare-up) if you stop taking Hepcludex.

Preparing and Injecting Hepcludex

Hepcludex comes as a powder that must be mixed with Sterile Water for Injection.

• The sterile water will be provided by your pharmacy along with syringes, transfer needles, and injection needles. Use only pharmacy-supplied Sterile Water for Injection, not tap or bottled water
• Once mixed, use Hepcludex immediately and discard any remainder.
• Each sterile water vial is single-use only; discard after use
• Never touch the needle or syringe tips; discard and replace if contact occurs
• Never reuse any supplies; dispose of all needles in a sharps container
• See the Hepcludex Instructions for Use for full preparation and administration information.

Hepcludex comes with a Boxed Warning for severe acute exacerbations of HDV and HBV after Hepcludex is discontinued, especially in patients with cirrhosis, who may be at increased risk of more severe flares or progression to hepatic decompensation.

• Worsening of hepatitis delta virus (HDV) and hepatitis B virus (HBV) infection. Your HDV or HBV infection may get worse (flare-up) if you stop taking Hepcludex, especially if you have cirrhosis. A "flare-up" is when your HDV or HBV infection suddenly returns in a worse way than before. Do not run out of Hepcludex. Refill your prescription or talk to your healthcare provider before your Hepcludex is all gone. Do not stop taking Hepcludex without first talking to your healthcare provider. If you stop taking Hepcludex, your healthcare provider will need to check your health often and do blood tests regularly for at least 6 months to check your liver, and may give you medicine to treat your viral infection. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking Hepcludex.

Before receiving Hepcludex, tell your healthcare provider about all your medical conditions, including if you:

• Are pregnant or plan to become pregnant. It is not known if Hepcludex can harm your unborn baby.
• Are breastfeeding or plan to breastfeed. It is not known if Hepcludex can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with Hepcludex.

It is not known if Hepcludex is safe and effective in children less than 18 years of age.

Hepcludex can cause serious side effects, such as:

• Allergic reactions, including severe allergic reactions (anaphylaxis). Stop taking Hepcludex and tell your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of a severe allergic reaction, including: trouble swallowing or breathing throat tightness severe rash, hives, or itching swelling of the mouth, lips, tongue, or face dizziness or fainting stomach area pain, nausea, diarrhea, or vomiting.

The most common side effects of Hepcludex include:

• injection site reactions, including infection, redness, itching, swelling, bruising, rash, and pain at the injection site
• headache
• stomach area pain
• feeling tired
• itchy skin.

These are not all of the possible side effects of Hepcludex. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Dose of Hepcludex for chronic HDV infection

• 8.5 mg subcutaneously once daily

Follow the Instructions for Use for preparation and administration of Hepcludex.

Hepcludex works by blocking the virus from entering liver cells (hepatocytes). It does this by binding to a protein on the surface of liver cells called NTCP, the receptor that HDV uses to attach and gain entry. By occupying this receptor, Hepcludex prevents HDV from latching on and infecting the cell.

The active ingredient, bulevirtide, is a synthetic lipopeptide, which is a small protein-like molecule consisting of 47 amino acids. It is derived from a specific region of the hepatitis B virus surface protein (the preS1 domain of L-HBsAg), and has been chemically modified at both ends to enhance its stability and function.

Hepcludex belongs to the drug class called sodium taurocholate co-transporting polypeptide (NTCP)-directed HDV attachment inhibitors.

If you miss a dose, take that dose as soon as possible on that day. However, if it is almost time for your next dose, skip the missed dose and go back to the regular dosing schedule.

If you take too much Hepcludex, call your healthcare provider or go to the nearest hospital emergency room right away.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Hepcludex (bulevirtide) is not expected to affect the levels or activity of other drugs. At clinically relevant concentrations, bulevirtide does not inhibit or induce CYP enzymes or drug transporters in a meaningful way.

Other drugs are unlikely to significantly affect how the body processes Hepcludex. Because bulevirtide is broken down through normal peptide catabolism rather than through CYP enzymes, the typical pathways by which drugs interfere with each other's metabolism do not apply here.

Store Hepcludex vials at room temperature between 68 °F and 77 °F (20 °C and 25 °C).

After mixing, use the Hepcludex vial right away. Throw away (discard) the unused portion.

Keep Hepcludex and all medicines out of reach of children.

Active ingredient: bulevirtide-gmod

Inactive ingredients: histidine, mannitol, and sucrose, and may include hydrochloric acid and/or sodium hydroxide for pH adjustment.

Supplied as bulevirtide 8.5 mg as a lyophilized powder or cake, in a single-dose vial.

Each carton contains a 30-day supply (30 vials).

Hepcludex is manufactured by Gilead Sciences, Inc., Foster City, CA 94404 U.S. License No. 2258.