Gavreto

Approved Uses

Gavreto is used to treat adults and certain pediatric patients with cancers that have spread or are advanced and possess a specific genetic alteration known as RET (rearranged during transfection). It is indicated for the following conditions:

• Non-Small Cell Lung Cancer (NSCLC): It is used in adults with metastatic NSCLC that is RET fusion-positive.
• Medullary Thyroid Cancer (MTC): It is used in adults and children aged 12 years and older with advanced or metastatic MTC that is RET-mutant and requires systemic therapy.
• Thyroid Cancer: It is used in adults and children aged 12 years and older with advanced or metastatic thyroid cancer that is RET fusion-positive, requires systemic therapy, and has not responded to radioactive iodine treatment (if that treatment was appropriate).

Genetic Testing

Because Gavreto specifically targets the RET protein, healthcare providers must confirm the presence of a RET gene fusion or mutation using a specialized laboratory test before starting treatment. This medication is only intended for patients whose tumors have these specific genetic markers.

Status of Approval

Some uses for Gavreto were granted accelerated approval based on initial study results showing how well the drug shrank tumors and how long the response lasted. Continued approval for these uses may depend on the results of ongoing clinical trials to confirm its clinical benefit.

Targeting RET Proteins

Gavreto belongs to a class of medications known as kinase inhibitors. It specifically targets a protein called RET (Rearranged during Transfection). In certain types of cancer, such as non-small cell lung cancer and thyroid cancer, the RET gene may be fused with another gene or mutated. These genetic changes cause the RET protein to become overactive.

An overactive RET protein acts like a switch that is stuck in the "on" position, sending constant signals to cells to divide and grow. This leads to the development and spread of cancerous tumors.

How Gavreto Works

Gavreto is designed to interfere with this signaling process through the following actions:

• Inhibition: The drug binds to the abnormal RET proteins, blocking their ability to send growth signals.
• Slowing Progression: By stopping these signals, Gavreto helps to slow or stop the growth of cancer cells.
• Selectivity: As a targeted therapy, it is specifically designed to act on cells with RET alterations, which may help limit damage to healthy cells that do not have these specific changes.

Common Side Effects

Many people taking Gavreto experience mild to moderate side effects. These may include:

• Feeling tired or weak
• Constipation
• Muscle, bone, or joint pain
• High blood pressure
• Decreased appetite
• Diarrhea
• Fluid retention or swelling

Gavreto can also cause changes in blood tests, such as decreased levels of white blood cells, red blood cells, or platelets. It may also affect liver function tests or mineral levels in the blood.

Serious Side Effects

While less common, some side effects can be severe and require immediate medical attention. Contact a healthcare provider right away if you experience symptoms of:

• Lung problems: New or worsening cough, shortness of breath, or chest pain, which may indicate lung inflammation (pneumonitis).
• Liver toxicity: Yellowing of the skin or eyes, dark urine, pain on the right side of the stomach, or unusual bruising.
• Severe high blood pressure: Headaches, dizziness, or blurred vision.
• Bleeding issues: Unusual bleeding, nosebleeds, or coughing up blood.
• Wound healing problems: Gavreto may interfere with how the body heals after surgery.

Lung Inflammation

Gavreto may cause severe, life-threatening, or fatal inflammation of the lungs, known as interstitial lung disease (ILD) or pneumonitis. Healthcare providers monitor for new or worsening respiratory symptoms, such as shortness of breath, cough, or fever. If these symptoms occur, treatment may be interrupted, reduced, or permanently stopped.

High Blood Pressure

High blood pressure (hypertension) is a common side effect and can become severe. It is standard practice to ensure blood pressure is controlled before starting treatment and to monitor it regularly during therapy. Dose adjustments or the addition of blood pressure medications may be required.

Liver Toxicity

This medication can cause elevations in liver enzymes, which may indicate liver damage. Liver function tests are typically performed before starting Gavreto and periodically throughout treatment. Significant elevations may require a dose reduction or treatment interruption.

Bleeding Risks

Serious and sometimes fatal bleeding (hemorrhage) can occur. Healthcare providers monitor for signs of unusual bleeding or bruising. Treatment may be discontinued if severe bleeding occurs.

Wound Healing Complications

Gavreto may interfere with the body's ability to heal wounds. It is generally recommended to stop taking the medication for at least one week before elective surgery and for at least two weeks after surgery until the wound is adequately healed.

Tumor Lysis Syndrome

Patients with rapidly growing tumors may be at risk for tumor lysis syndrome (TLS), a condition where cancer cells break down quickly and release substances into the blood. This can lead to kidney failure or heart rhythm problems. Monitoring for signs of TLS is common during treatment.

Embryo-Fetal Toxicity

Gavreto can cause harm to a developing fetus. Effective contraception is recommended for females of reproductive potential and for males with female partners of reproductive potential during treatment and for a period after the final dose.

Pregnancy

Gavreto can cause fetal harm when administered to a pregnant person. Based on its mechanism of action and findings from animal studies, the medication may lead to embryo-fetal toxicity or birth defects. Healthcare providers typically require a pregnancy test to ensure a patient is not pregnant before starting treatment.

Effective contraception is recommended for patients of reproductive potential:

• Females: Use effective non-hormonal birth control during treatment and for at least 2 weeks after the final dose. Gavreto may reduce the effectiveness of hormonal contraceptives.
• Males: Those with female partners of reproductive potential should use effective contraception during treatment and for at least 1 week after the final dose.

If you become pregnant or think you might be pregnant while taking this medication, contact your healthcare provider immediately to discuss the potential risks.

Breastfeeding

There is no information regarding the presence of Gavreto in human breast milk or its effects on a breastfed child. Because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for 1 week after the last dose.

Dosage Forms

Gavreto is supplied in the following form for oral administration:

• Capsule: This medication is provided as a capsule to be swallowed whole on an empty stomach.

FDA Approval Status

Gavreto received its initial approval from the FDA in 2020. It is a kinase inhibitor targeted therapy. Several of its indications were approved under the FDA's accelerated approval pathway, which is used for drugs that treat serious conditions and fill an unmet medical need based on promising early data.

Approved Indications

Gavreto is currently FDA-approved for the treatment of adults and certain pediatric patients with the following conditions:

• Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC): For adult patients whose cancer has spread to other parts of the body.
• RET-Mutant Medullary Thyroid Cancer (MTC): For adults and pediatric patients aged 12 years and older with advanced or metastatic disease who require systemic therapy.
• RET Fusion-Positive Thyroid Cancer: For adults and pediatric patients aged 12 years and older with advanced or metastatic disease who require systemic therapy and whose cancer did not respond to radioactive iodine treatment.

Regulatory Requirements and Monitoring

Because some uses were granted accelerated approval, the manufacturer may be required to conduct further clinical trials to confirm the drug's long-term clinical benefit. Continued approval for these specific indications may depend on the results of these confirmatory trials.

There are currently no boxed warnings or Risk Evaluation and Mitigation Strategy (REMS) programs required for Gavreto. The FDA continues to monitor the safety and effectiveness of the medication through standard post-marketing surveillance and adverse event reporting systems.

Insurance and Pharmacy Factors

The price you pay for Gavreto can vary based on your insurance plan. Most commercial insurance plans and Medicare Part D cover this medication, but it is often classified as a specialty drug. This classification may place it on a higher cost tier, which can result in a higher co-pay or coinsurance amount.

Gavreto is typically dispensed through specialty pharmacies. These pharmacies specialize in medications that require unique handling, storage, or monitoring. The cost may differ between these providers depending on their specific contracts with insurance companies.

Financial Assistance Programs

Because Gavreto is a brand-name specialty medication, the manufacturer often provides programs to help reduce the financial burden for patients. These may include:

• Co-pay Savings Cards: These are often available to patients with commercial (private) insurance to help lower out-of-pocket costs.
• Patient Assistance Programs: These programs may provide the medication at no cost or a significantly reduced cost for individuals who are uninsured or underinsured and meet certain income requirements.

Generic Availability

There is currently no generic version of Gavreto (pralsetinib) available. Generic drugs usually cost less than brand-name drugs, but because Gavreto is a newer targeted therapy, it remains available only as a brand-name product. The lack of generic competition contributes to its higher price point.