Imbruvica (ibrutinib) is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, jointly developed and commercialized by Janssen and Pharmacyclics.

It is an oral therapy approved, either alone or in combination with other therapies, for many B-cell non-Hodgkin’s lymphomas (NHL), including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL).

The drug was also approved by the U.S Food and Drug Administration (FDA) to treat chronic graft versus host disease (GvHD) that may develop following a transplant, and Waldenström’s macroglobulinemia, another type of NHL. In addition, the drug is also being evaluated for the treatment of follicular lymphoma (FL).

B-cell non-Hodgkin’s lymphoma originates in B-cells at the lymph nodes. B-cells are a type of immune system cell and are responsible for combating infections or threats through the production of antibodies.

How Imbruvica works

Treatments for lymphoma now include targeted therapies that aim to kill the type of cell that has turned cancerous or to stop signals that make cancerous cells grow, divide, and spread through the body. Targeted treatment can have fewer side effects as they may not affect other types of cells.

Imbruvica is a cell signaling inhibitor that works by blocking the activity of BTK, a specific protein that is a part of a biologic pathway that helps B-cells stay alive and divide. By forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells, Imbruvica helps kill and reduce the number of cancerous B-cells. This stops or slows down the progression of the cancer.

Imbruvica in clinical trials

Imbruvica was first evaluated in a Phase 1 dose-escalation trial (NCT00849654) to determine its maximum tolerable dose, safety, pharmacokinetics, pharmacodynamics, and tumor response. Fifty-six patients with various types of B-cell NHL were enrolled in the study. The study’s results showed that the drug was well tolerated across various types of B-cell non-Hodgkin’s lymphoma.

The U.S. Food and Drug Administration (FDA) approved Imbruvica in 2013 for the treatment of patients with mantle cell lymphoma (MCL), based on the results of an open-label, Phase 2 study (NCT01236391), where 111 patients who had received at least one prior therapy were given Imbruvica daily until their disease progressed or side effects became intolerable. The results of this trial showed that nearly 66 percent of participants saw their cancer shrink or disappear after treatment (called the overall response rate).

Also in 2013, the FDA approved Imbruvica for the treatment of chronic lymphocytic leukemia (CLL). The decision was based on the results of a Phase 1b/2 trial (NCT01105247), in which 85 patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL) received Imbruvica. Results showed that nearly 58 percent of participants had their cancer shrink after treatment.

In 2015, the FDA approved Imbruvica as a first-line treatment for CLL based on the results of an open-label Phase 3 clinical trial (NCT01722487).

In early 2017, the FDA approved Imbruvica as a first-line treatment specifically indicated for relapsed/refractory marginal zone lymphoma (MZL) patients. The approval was based on data from an open-label, Phase 2 study (NCT01980628) which evaluated the safety and efficacy of Imbruvica in 63 MZL patients. The results produced meaningful tumor shrinkage and the treatment was well tolerated overall.

Imbruvica is currently being tested in several other clinical trials for the treatment of various types of B-cell lymphomas alone or in combination with other drugs.

For example, a Phase 3 clinical trial (NCT02947347)  is currently recruiting patients with follicular lymphoma that has not been previously treated. The purpose of this study is to evaluate whether the addition of Imbruvica to Rituxan (rituximab) will result in the prolongation of the length of time that a patient lives with the disease compared to when they are treated with Rituxan alone.

Other details

The most common side effects caused by Imbruvica include diarrhea, muscle and bone pain, rash, nausea, bruising, tiredness, and fever.

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