Brukinsa

Approved Uses

Brukinsa is used to treat the following conditions in adults:

• Mantle cell lymphoma (MCL): It is prescribed for patients who have already received at least one prior treatment for their cancer.
• Waldenström’s macroglobulinemia (WM): This is a rare type of slow-growing non-Hodgkin lymphoma.
• Marginal zone lymphoma (MZL): It is used when the cancer has returned or did not respond to at least one previous treatment that included a specific type of medicine called an anti-CD20 antibody.
• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): These are cancers that affect the white blood cells and lymph nodes.
• Follicular lymphoma (FL): It is used in combination with another medication called obinutuzumab for adults whose cancer has returned or did not respond after at least two prior types of treatment.

This medication is typically used when cancer is relapsed (it came back after treatment) or refractory (it did not respond to previous treatment).

Mechanism of Action

Brukinsa belongs to a class of medications known as Bruton's tyrosine kinase (BTK) inhibitors. It is designed to target and interfere with the signaling pathways that allow certain blood cancers to progress.

Targeting B-cells

The medication works by focusing on B-cells, which are a type of white blood cell. In healthy individuals, B-cells help the immune system fight infections. However, in people with certain types of lymphoma or leukemia, these B-cells become cancerous and multiply uncontrollably.

Blocking the BTK Protein

Inside these cancerous B-cells is a protein called Bruton's tyrosine kinase. This protein acts as a signaling molecule that tells the cancer cells to grow, divide, and stay alive. Brukinsa works by:

• Binding to the BTK protein.
• Blocking the signals that the protein sends to the rest of the cell.
• Preventing the cancer cells from multiplying and spreading.

By inhibiting this specific protein, the drug helps to reduce the number of cancer cells in the body and may lead to the death of existing cancer cells.

Common Side Effects

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

• Decreased white blood cell, red blood cell, or platelet counts
• Upper respiratory tract infections or cough
• Bruising or small red or purple spots on the skin
• Diarrhea
• Muscle, bone, or joint pain
• Rash

Serious Side Effects

Some side effects can be severe and require immediate medical attention. Contact your healthcare provider right away if you experience any of the following:

• Severe bleeding: Signs include blood in the stool or urine, coughing up blood, or unusual or heavy bleeding that will not stop.
• Infections: Fever, chills, or flu-like symptoms may indicate a serious infection, such as pneumonia or sepsis.
• Heart rhythm problems: Symptoms include a fast or irregular heartbeat, dizziness, fainting, or chest discomfort.
• Second primary cancers: New cancers, including skin cancers, have occurred in some patients during treatment.
• Tumor Lysis Syndrome: This condition is caused by the rapid breakdown of cancer cells and can lead to kidney failure or abnormal heart rhythms.

Serious Bleeding

Brukinsa can cause serious or life-threatening bleeding (hemorrhage). This risk may be higher for individuals also taking blood thinners or antiplatelet medications. Healthcare providers may recommend pausing the medication before and after planned surgical procedures.

Infections

Treatment may increase the risk of severe bacterial, viral, or fungal infections, including pneumonia and skin infections. In some cases, these infections can be fatal. It is important to monitor for signs of infection, such as fever or chills.

Low Blood Cell Counts

This medication can significantly decrease blood cell counts, including:

• Neutropenia: Low white blood cells, which increases infection risk.
• Thrombocytopenia: Low platelets, which increases bleeding risk.
• Anemia: Low red blood cells.

Regular complete blood count tests are typically performed to monitor these levels during treatment.

Heart Rhythm Problems

Atrial fibrillation and atrial flutter (irregular heartbeats) have occurred in patients taking Brukinsa. The risk may be higher for those with existing heart disease, high blood pressure, or diabetes. Monitoring for symptoms like palpitations, dizziness, or shortness of breath is important.

Second Primary Malignancies

There is an increased risk of developing other types of cancer while taking this medication, most commonly skin cancers. Using sun protection and monitoring for new or changing skin lesions is often advised.

Tumor Lysis Syndrome

This condition occurs when cancer cells break down rapidly, releasing their contents into the bloodstream. This can cause kidney failure or heart rhythm issues and requires medical monitoring.

Pregnancy and Reproduction

Brukinsa can cause fetal harm if taken during pregnancy. Effective contraception should be used by both females and males with female partners of reproductive potential during treatment and for a specified time after the final dose.

Pregnancy

Brukinsa can cause harm to an unborn baby. Based on animal studies and the way the medication works, it may lead to fetal harm when administered to a pregnant woman. It is important to discuss pregnancy status and plans with a healthcare provider before starting treatment.

To prevent pregnancy during treatment, the following measures are generally advised:

• Females of reproductive potential should use effective birth control during treatment and for at least one week after the last dose.
• Males with female partners of reproductive potential should use effective birth control during treatment and for at least one week after the last dose.

If pregnancy occurs while taking this medication, it should be reported to a healthcare provider immediately.

Breastfeeding

There is no information on whether Brukinsa is present in human breast milk or how it might affect a nursing child. Due to the risk of serious adverse reactions, breastfeeding is not recommended during treatment and for at least two weeks after the final dose.

Available Forms

Brukinsa is supplied as a capsule to be taken by mouth. It is intended to be swallowed whole and can be administered with or without food.

• Oral capsule

FDA Approved Indications

Brukinsa is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with the following conditions:

• Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL): Approved for use in adult patients.
• Waldenström’s Macroglobulinemia (WM): Approved for use in adult patients.
• Mantle Cell Lymphoma (MCL): Approved for patients who have received at least one prior therapy.
• Marginal Zone Lymphoma (MZL): Approved for patients with relapsed or refractory disease who have received at least one prior anti-CD20-based regimen.
• Follicular Lymphoma (FL): Approved for use in combination with obinutuzumab for patients with relapsed or refractory disease after at least two prior lines of systemic therapy.

Accelerated Approval Status

The approvals for mantle cell lymphoma, marginal zone lymphoma, and follicular lymphoma were granted under the FDA's accelerated approval pathway. This program allows for the earlier approval of drugs that treat serious conditions and fill an unmet medical need based on clinical trial data showing an effect on a surrogate endpoint, such as the overall response rate. Continued approval for these specific uses may be contingent upon the verification of clinical benefit in confirmatory trials.

Regulatory Safety Information

As of the most recent labeling, Brukinsa does not carry a boxed warning, which is the FDA’s most serious type of warning. There is also no Risk Evaluation and Mitigation Strategy (REMS) program required for this medication. The FDA continues to monitor the safety profile of the drug through standard post-marketing surveillance.

Factors Influencing Cost

The actual price you pay for Brukinsa depends on several factors, including your insurance plan, your treatment schedule, and the pharmacy you use. Because it is a specialty medication, it may not be available at all retail pharmacies and often requires a specialty pharmacy provider.

Generic Status

Brukinsa is a brand-name drug. There is currently no generic version of zanubrutinib available. Brand-name medications typically cost more than generic versions because of the research and development involved.

Financial Assistance

Many patients use insurance to help cover the cost of Brukinsa. For those without insurance or whose insurance does not cover the full cost, financial assistance programs may be available. These can include:

• Manufacturer-sponsored patient assistance programs.
• Copay savings cards for eligible patients with commercial insurance.
• Support from independent charitable foundations that help with out-of-pocket costs for chronic or life-threatening conditions.