Zanubrutinib

Approved Conditions

Zanubrutinib is used to treat the following conditions in adults:

• Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL): These are cancers that affect white blood cells.
• Mantle Cell Lymphoma (MCL): It is used for patients who have 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 prior treatment that included an anti-CD20-based medicine.
• Follicular Lymphoma (FL): It is used in combination with another medicine called obinutuzumab for patients whose cancer has returned or did not respond after at least two prior lines of systemic therapy.

How It Is Used

Zanubrutinib belongs to a class of drugs known as kinase inhibitors. It works by blocking the action of a specific protein that helps cancer cells grow and multiply. For certain conditions, such as mantle cell lymphoma and marginal zone lymphoma, the medication was granted accelerated approval based on early clinical evidence. Continued approval for these specific uses may depend on the results of further clinical trials to confirm its effectiveness.

Targeting BTK

Zanubrutinib is classified as a Bruton's tyrosine kinase (BTK) inhibitor. BTK is a protein that plays a critical role in the development and activation of B-cells, which are a type of white blood cell. In healthy individuals, BTK helps these cells grow and function as part of the immune system.

In certain blood cancers, the BTK protein becomes overactive. This overactivity sends continuous signals to the B-cells, causing them to multiply rapidly and survive longer than normal. This process leads to the formation of tumors or the accumulation of cancerous cells in the blood and bone marrow.

Zanubrutinib works by binding to the BTK protein and blocking its activity. By shutting down this signaling pathway, the medication helps to:

• Inhibit cell growth: It prevents the cancer cells from receiving the instructions they need to divide.
• Promote cell death: Without the survival signals provided by BTK, the cancerous cells may die off.
• Limit cancer spread: It helps slow or stop the progression of the disease throughout the body.

Because zanubrutinib specifically targets the BTK protein, it is designed to interfere with cancer cell survival while potentially minimizing effects on other types of healthy cells.

Common Side Effects

• Decreased white blood cell, red blood cell, or platelet counts
• Upper respiratory tract infections
• Cough
• Muscle, bone, or joint pain
• Rash
• Diarrhea
• Tiredness or fatigue
• Bruising

Serious Side Effects

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

• Severe bleeding: This includes blood in the stool or urine, coughing up blood, or unexplained bruising.
• Infections: Symptoms such as fever, chills, or persistent cough.
• Heart rhythm problems: Signs include a racing or fluttering heartbeat, chest discomfort, or feeling lightheaded.
• Second primary cancers: Development of new skin cancers or other malignancies.
• Tumor Lysis Syndrome: Symptoms resulting from the rapid breakdown of cancer cells, such as nausea, vomiting, or confusion.

Serious Bleeding

Zanubrutinib can cause serious and sometimes fatal bleeding events. The risk of hemorrhage is increased in patients who are also taking antiplatelet or anticoagulant medications. Treatment may need to be interrupted for several days before and after surgical procedures to reduce the risk of bleeding.

Infections

Fatal and serious infections, including pneumonia and other bacterial, viral, or fungal infections, have occurred. Healthcare providers monitor for signs of infection and may prescribe preventive medications for patients at increased risk. Reactivation of hepatitis B virus has also been reported in some cases.

Blood Cell Counts

Decreases in blood cell counts, including neutropenia (low white blood cells), thrombocytopenia (low platelets), and anemia (low red blood cells), are common. Regular monitoring of complete blood counts is necessary to manage these risks and determine if dose adjustments or treatment interruptions are needed.

Heart Rhythm Issues

Atrial fibrillation and atrial flutter have been observed in patients treated with this medication. Monitoring for heart rhythm disturbances is recommended, especially for those with existing cardiac risk factors, high blood pressure, or acute infections.

Second Primary Malignancies

There is an increased risk of developing new cancers, particularly skin cancers, while taking zanubrutinib. Protection from sun exposure and regular skin examinations are advised during treatment.

Fetal Harm

Zanubrutinib can cause harm to an unborn baby. Females of reproductive potential and males with female partners of reproductive potential are advised to use effective contraception during treatment and for a specified time after the last dose.

Pregnancy

Zanubrutinib can cause fetal harm when used during pregnancy. Healthcare providers typically require a pregnancy test for individuals of reproductive potential before starting treatment.

To prevent pregnancy, effective contraception must be used:

• Females: Use effective birth control during treatment and for at least 1 week after the final dose.
• Males: Men with female partners of reproductive potential should use effective birth control during treatment and for at least 1 week after the final dose.

If you become pregnant while taking zanubrutinib, notify your healthcare provider immediately.

Breastfeeding

It is not known if zanubrutinib passes into breast milk. Because of the potential for serious adverse reactions in a nursing child, you should not breastfeed during treatment and for at least 2 weeks after the final dose.

Available Forms

Zanubrutinib is available as a capsule for oral administration. It is intended to be swallowed whole with water and should not be opened, crushed, or chewed.

This medication can be taken with or without food.

FDA Approval and Indications

The U.S. Food and Drug Administration (FDA) first approved zanubrutinib in 2019. It is currently indicated for the treatment of adult patients with the following conditions:

• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• Waldenström’s macroglobulinemia (WM).
• Mantle cell lymphoma (MCL) in patients who have received at least one prior therapy.
• Marginal zone lymphoma (MZL) in patients who have received at least one prior anti-CD20-based regimen.
• Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after at least two lines of systemic therapy.

Regulatory Status

Several of zanubrutinib's indications, such as those for mantle cell lymphoma, marginal zone lymphoma, and follicular lymphoma, were granted under the FDA's accelerated approval pathway. This pathway allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint. Continued approval for these specific uses may be contingent upon verification of clinical benefit in confirmatory trials.

Safety and Monitoring

There are currently no Boxed Warnings or Risk Evaluation and Mitigation Strategies (REMS) required for zanubrutinib. However, the FDA labeling includes information regarding pharmacogenomic biomarkers, specifically related to the BTK protein which the drug targets. The medication is available only by prescription and is typically dispensed through specialty pharmacies.

FDA-Approved Indications

The U.S. Food and Drug Administration (FDA) has approved zanubrutinib for the treatment of adult patients with the following conditions:

• Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL): Approved for patients with these types of cancer.
• Waldenström’s Macroglobulinemia (WM): Approved for adults with this rare type of B-cell lymphoma.
• 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 MZL who have received at least one anti-CD20-based regimen.
• Follicular Lymphoma (FL): Approved for use in combination with obinutuzumab for patients with relapsed or refractory FL after at least two prior lines of systemic therapy.

Accelerated Approval

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

Pharmacogenomics

The FDA includes zanubrutinib in its table of pharmacogenomic biomarkers in drug labeling. The drug targets the Bruton's tyrosine kinase (BTK) protein, and its efficacy is related to its interaction with this specific biomarker in B-cell malignancies.