Rybrevant

Approved Indications

Rybrevant is used to treat adults with non-small cell lung cancer (NSCLC) that is locally advanced or metastatic. It is specifically prescribed for patients whose cancer has certain mutations in the epidermal growth factor receptor (EGFR) gene.

The medication is used in the following situations:

• EGFR Exon 20 Insertion Mutations: Rybrevant may be used as a single treatment if the cancer has progressed after receiving platinum-based chemotherapy. It is also approved for use as a first-line treatment in combination with carboplatin and pemetrexed.
• EGFR Exon 19 Deletions or L858R Substitution Mutations: It is used in combination with lazertinib as a first-line treatment for patients with these specific mutations.

Administration and Testing

A healthcare provider must confirm the presence of specific EGFR mutations using an FDA-approved test before treatment begins. Rybrevant is administered by a healthcare professional as an intravenous infusion or as a subcutaneous injection.

Mechanism of Action

Rybrevant is a bispecific antibody, which is a type of protein designed to recognize and attach to two different targets simultaneously. In the case of non-small cell lung cancer, it targets two specific receptors on the surface of cancer cells:

• EGFR (Epidermal Growth Factor Receptor): A protein that can cause cells to grow and divide.
• MET (Mesenchymal-Epithelial Transition): Another protein involved in cell growth and survival.

By binding to both EGFR and MET, Rybrevant blocks the signals that these proteins normally send to tell the cancer cells to multiply. This helps to slow down or stop the progression of the disease.

Beyond blocking growth signals, Rybrevant also works by marking the cancer cells so that the body's own immune system can find and destroy them. This dual approach helps target the cancer directly while also enlisting the immune system's help.

Common Side Effects

• Rash
• Infusion-related reactions
• Nail infections (paronychia)
• Muscle or joint pain
• Shortness of breath
• Feeling tired or weak
• Nausea and vomiting
• Swelling of the hands, ankles, or feet
• Sores in the mouth
• Cough
• Constipation
• Dry skin

Serious Side Effects

Seek medical attention immediately if you experience any of the following serious symptoms:

• Lung problems: New or worsening shortness of breath, cough, or fever, which may indicate interstitial lung disease or pneumonitis.
• Severe skin reactions: Blistering, peeling skin, or a rash that covers a large area of the body.
• Eye problems: Vision changes, eye pain, redness, or excessive tearing.
• Infusion reactions: Chills, fever, dizziness, or nausea occurring during or shortly after the treatment.
• Blood clots: Pain or swelling in the legs, or sudden chest pain and difficulty breathing.

Infusion-Related Reactions

Many patients experience reactions during the administration of Rybrevant, especially with the first dose. Symptoms can include fever, chills, nausea, chest discomfort, or shortness of breath. Medical teams usually provide premedication to help prevent or lessen these effects.

Lung Inflammation

Rybrevant can cause interstitial lung disease or pneumonitis, which are serious conditions involving inflammation of the lungs. Symptoms like a new or worsening cough, fever, or trouble breathing require immediate medical attention, as these conditions can be life-threatening.

Skin and Nail Issues

Skin rashes are a frequent side effect and can sometimes become severe. Because sunlight can make these rashes worse, it is important to use sunscreen and wear protective clothing while outdoors. The medication can also cause inflammation, pain, or infection in the skin around the fingernails and toenails.

Eye Complications

This treatment may cause eye problems, including redness, pain, dryness, or changes in vision. If these symptoms occur, a referral to an eye specialist may be necessary to prevent further complications.

Pregnancy and Reproductive Health

Rybrevant can cause harm to an unborn baby if used during pregnancy. Effective contraception is recommended for those of reproductive potential during treatment and for three months after the last dose. It is also advised to avoid breastfeeding while receiving this medication.

Pregnancy

Rybrevant can cause fetal harm if used during pregnancy. Based on its mechanism of action and findings from animal studies, this medication may interfere with normal fetal development. Healthcare providers typically require a pregnancy test before starting treatment to ensure the patient is not pregnant.

Individuals who are able to become pregnant should use effective birth control (contraception) during treatment and for at least 3 months after the final dose of Rybrevant. If a patient becomes pregnant or thinks they might be pregnant while receiving this medication, they should contact their healthcare provider immediately to discuss the potential risks to the fetus.

Breastfeeding

It is not known whether Rybrevant passes into human breast milk or if it has any effect on a nursing infant. Because of the potential for serious adverse reactions in a breastfed child, it is generally advised that patients do not breastfeed during treatment and for 3 months after the last dose. Patients should discuss their options for infant feeding with their healthcare team.

Available Forms

Rybrevant is available as a concentrated solution for injection. It is administered in a medical setting using the following methods:

• Intravenous Infusion: The medication is diluted and given through a vein.
• Subcutaneous Injection: A specific formulation is available for injection into the tissue under the skin.

The medication is supplied in vials and must be prepared and administered by a trained healthcare provider.

FDA Approval and Indications

Rybrevant (amivantamab-vmjw) was first granted accelerated approval by the U.S. Food and Drug Administration (FDA) in 2021. It is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as determined by an FDA-approved test.

The medication is approved for use in the following clinical settings:

• As a single agent for patients whose disease has progressed on or after platinum-based chemotherapy.
• In combination with carboplatin and pemetrexed for the first-line treatment of patients with EGFR exon 20 insertion mutations.

Subcutaneous Formulation

In 2024, the FDA approved a subcutaneous formulation (amivantamab and hyaluronidase-lpuj). This version is approved for the same indications as the intravenous form but offers a significantly shorter administration time and may reduce the frequency of infusion-related reactions.

Regulatory Requirements and Monitoring

The use of Rybrevant is contingent upon the presence of specific biomarkers. Patients must have their tumors tested for EGFR exon 20 insertion mutations before starting therapy. Because some indications were approved under the FDA's accelerated approval pathway based on tumor response rate and duration of response, continued approval may be dependent upon verification of clinical benefit in confirmatory trials.

Factors Affecting Cost

The total price of Rybrevant treatment can vary significantly based on several factors:

• Insurance Coverage: Your out-of-pocket expenses, such as copays or coinsurance, are determined by your specific health insurance plan.
• Dosage and Frequency: Because Rybrevant is often dosed based on body weight, the amount of medication needed for each infusion or injection affects the cost.
• Administration Fees: Since Rybrevant must be administered by a healthcare professional in a clinical setting, there may be additional charges for the facility and the administration procedure.

Financial Assistance

The manufacturer of Rybrevant offers programs to help patients manage the cost of the medication. These may include:

• Copay Support: Patients with commercial insurance may be eligible for copay cards that reduce out-of-pocket costs.
• Patient Assistance Programs: Individuals who are uninsured or underinsured may qualify for programs that provide the medication at a lower cost or for free, depending on financial eligibility.

Generic Availability

Rybrevant is a brand-name biologic medication, and there is currently no generic or biosimilar version available. Brand-name specialty medications typically have higher costs than generic drugs.

Insurance and Medicare

Many insurance plans, including Medicare and Medicaid, cover Rybrevant for its approved uses. However, most insurers require prior authorization, a process where your doctor must prove the medical necessity of the drug before the insurance company agrees to pay for it.