Empaveli

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Empaveli is specifically approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults. PNH is a rare genetic condition that causes the immune system to prematurely destroy red blood cells. This destruction, known as hemolysis, can lead to low red blood cell counts (anemia), fatigue, pain, and life-threatening blood clots.

This medication may be prescribed for individuals in the following situations:

• Adults who have not previously received treatment for PNH.
• Adults who are switching to Empaveli after being treated with other complement inhibitor medications.

The goal of treatment is typically to improve hemoglobin levels and reduce the frequency of blood transfusions required by the patient.

Targeting the Complement System

Empaveli belongs to a class of medications called complement inhibitors. In people with PNH, a part of the immune system known as the complement system mistakenly attacks and destroys red blood cells. This process of red blood cell destruction is called hemolysis.

Blocking the C3 Protein

The medication works by binding to a protein called C3, which is a central component of the complement system. By blocking C3, Empaveli prevents the immune system from starting the chain reaction that leads to the destruction of red blood cells. This helps control two types of cell destruction:

• Intravascular hemolysis: This is the breakdown of red blood cells that occurs inside the blood vessels.
• Extravascular hemolysis: This is the destruction of red blood cells that occurs in the spleen or liver.

By reducing the breakdown of red blood cells, Empaveli helps increase hemoglobin levels in the blood and may reduce the frequency of blood transfusions for people with this condition.

Common Side Effects

Many people using Empaveli experience mild to moderate side effects. These often include:

• Injection site reactions, such as redness, pain, swelling, or itching where the medicine was administered.
• Upper respiratory tract infections, such as the common cold or sinus infections.
• Diarrhea or abdominal pain.
• Headache.
• Fatigue or general tiredness.
• Back pain.
• Nausea.
• Viral infections.

Serious Side Effects

Empaveli affects the immune system, which can increase the risk of serious and potentially life-threatening infections. Seek medical attention immediately if you experience symptoms such as fever, chills, a stiff neck, or a severe headache.

Other serious side effects may include:

• Severe allergic reactions (anaphylaxis), which may cause difficulty breathing, swelling of the face or throat, or a severe rash.
• Serious infections caused by specific types of bacteria, including those that cause meningitis, pneumonia, and sepsis.
• Infusion-related reactions that occur during or shortly after the administration of the drug.

Serious Infections

Empaveli can increase the risk of life-threatening infections caused by encapsulated bacteria, such as Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b. These infections can become fatal very quickly if they are not recognized and treated early.

Vaccination Requirements

Because of the risk of infection, individuals must receive vaccinations against these specific bacteria at least two weeks before starting treatment. If treatment must begin immediately and there is no time for vaccinations, healthcare providers may prescribe preventive antibiotics to be taken while the vaccines take effect.

REMS Program

Due to the risk of serious infections, Empaveli is only available through a restricted program called the Empaveli REMS (Risk Evaluation and Mitigation Strategy). Patients must be enrolled in the program and carry a patient safety card at all times to alert emergency medical personnel of the risk of certain infections.

Monitoring for Symptoms

It is important to monitor for early signs of infection and seek medical care immediately if any of the following occur:

• Fever or chills
• Headache with nausea or vomiting
• Stiff neck or stiff back
• Confusion
• Muscle aches with flu-like symptoms
• Sensitivity to light

Stopping Treatment

If treatment with Empaveli is interrupted or stopped, there is a risk of serious hemolysis, which is the rapid breakdown of red blood cells. Healthcare providers typically monitor patients closely for at least eight weeks after the last dose to check for signs of this condition, such as fatigue, shortness of breath, or dark urine.

Laboratory Test Interference

The use of Empaveli may interfere with certain laboratory tests, such as the Coombs test. This can lead to inaccurate results when testing for certain blood conditions.

Pregnancy

There is limited information regarding the safety of Empaveli in pregnant women. Animal studies have indicated that the medication may increase the risk of pregnancy loss when administered at high doses. Consequently, healthcare providers generally advise individuals who can become pregnant to use effective contraception during treatment and for at least 4 weeks following the last dose.

If you are pregnant or planning to become pregnant, discuss the potential risks and benefits of this medication with your healthcare provider.

Breastfeeding

It is currently unknown whether Empaveli passes into human breast milk or how it might affect a nursing infant. Because of the potential for adverse effects, it is important to consult with a healthcare provider to decide whether to continue breastfeeding or to stop the medication, based on the mother's medical needs.

Dosage Forms

Empaveli is supplied as a sterile, clear, colorless to slightly yellowish solution. It is intended for subcutaneous use only and should not be administered into a vein.

Packaging and Administration

• Single-dose vials: The medication is packaged in vials designed for a single use.
• Infusion method: It is administered using a specialized infusion pump and infusion sets that deliver the medicine into the tissue under the skin.

FDA Approval Status

The U.S. Food and Drug Administration (FDA) approved Empaveli (pegcetacoplan) in May 2021. It was the first FDA-approved PNH therapy that binds to complement protein C3 to help prevent the destruction of red blood cells. It is specifically indicated for use in adults with PNH.

Boxed Warning

Empaveli carries a Boxed Warning regarding the risk of serious and life-threatening infections caused by encapsulated bacteria. These include:

• Streptococcus pneumoniae
• Neisseria meningitidis (types A, C, W, Y, and B)
• Haemophilus influenzae type b (Hib)

To reduce this risk, patients must be vaccinated against these bacteria at least two weeks before starting treatment. If urgent treatment is required and vaccines are not up to date, healthcare providers must provide antibacterial drug prophylaxis.

REMS Program

Because of the risk of serious infections, Empaveli is available only through a restricted program called the Empaveli Risk Evaluation and Mitigation Strategy (REMS). Under this program, healthcare providers who prescribe the medication must be specially certified and must counsel patients about the risks of infection and the importance of vaccination.

Insurance and Out-of-Pocket Costs

The actual price you pay for Empaveli depends on your insurance coverage, your location, and the pharmacy you use. As a specialty drug, it is often placed on a high-tier formulary, which may result in higher copayments or coinsurance amounts. Most insurance plans require prior authorization before they will cover the cost of this medication.

Specialty Pharmacy Requirements

Empaveli is generally only available through specialty pharmacies. These pharmacies handle medications that require special handling, storage, or administration instructions. They can also help coordinate insurance approvals and explore financial aid options.

Financial Support Options

There are several resources available to help manage the cost of treatment:

• Manufacturer Support: The drug manufacturer may offer a copay savings program for patients with commercial insurance to help lower out-of-pocket expenses.
• Patient Assistance Programs: Non-profit organizations or the manufacturer may provide assistance to patients who are uninsured or meet certain financial criteria.

Patients are encouraged to contact their insurance provider or the manufacturer's support line to get the most accurate estimate of their treatment costs.