National Stroke Foundation

Imbruvica (ibrutinib)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved February 2014

Specific Treatments:

chronic lymphocytic leukemia and small lymphocytic lymphoma

Therapeutic Areas

General Information

Imbruvica (ibrutinib) is an orally available, selective inhibitor of Bruton's tyrosine kinase (Btk), a gene that is disrupted in the human disease X-linked agammaglobulenemia (XLA). BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways.

Imbruvica is specifically approved for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma and for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma who carry a deletion in chromosome 17 (17p deletion).

Imbruvica is supplied as a capsule for oral administration. The recommended dose is 420 mg taken orally once daily (three 140 mg capsules once daily). Capsules should be taken orally with a glass of water. Do not open, break, or chew the capsules.

Clinical Results

FDA Approval

The FDA approval of Imbruvica for chronic lymphocytic leukemia was based on an open-label, multi-center trial of 48 previously treated patients. Imbruvica was administered orally at 420 mg once daily until disease progression or unacceptable toxicity. The overall response rate (ORR) and duration of response (DOR) were assessed using a modified version of the International Workshop on CLL Criteria by an Independent Review Committee. The ORR was 58.3%, all partial responses. None of the patients achieved a complete response. The DOR ranged from 5.6 to 24.2+ months. The median DOR was not reached.

The FDA approved of Imbruvica for CLL with 17p deletion was based on a clinical study of 391 previously treated patients, 127 of whom had CLL with 17p deletion. The patients were randomly assigned to receive Imbruvica or Arzerra until disease progression or side effects became intolerable. The trial was stopped early for efficacy after a pre-planned interim analysis showed Imbruvica-treated patients experienced a 78 percent reduction in risk of disease progression or death (progression-free survival). Results also showed a 57 percent reduction in risk of death (overall survival) in patients treated with Imbruvica. Of the 127 patients who had CLL with 17p deletion, those treated with Imbruvica experienced a 75 percent reduction in risk of disease progression or death.

The FDA approval of Imbruvica as a first-line treatment for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) was based on data from the randomized, multi-center, open-label Phase 3 RESONATE-2 (PCYC-1115) trial, which evaluated the use of Imbruvica versus chlorambucil in 269 treatment-naïve patients with CLL or SLL aged 65 years or older. Imbruvica significantly prolonged progression-free survival (PFS; primary endpoint) as determined by an Independent Review Committee (IRC), reducing the risk of progression or death by 84% versus chlorambucil; median PFS: not reached for Imbruvica vs. 18.9 months for chlorambucil). Imbruvica was also associated with a significantly higher IRC-assessed overall response rate (ORR: a composite of complete and partial responses; 82.4% vs. 35.3%) versus chlorambucil. Five patients (3.7 percent) in the Imbruvica arm achieved a complete response, compared to two patients (1.5 percent) in the chlorambucil arm.

 

 

Side Effects

Adverse events associated with the use of Imbruvica may include, but are not limited to, the following:

  • thrombocytopenia
  • diarrhea
  • bruising
  • neutropenia
  • anemia
  • upper respiratory tract infection
  • fatigue
  • musculoskeletal pain
  • rash
  • pyrexia
  • constipation
  • peripheral edema
  • arthralgia
  • nausea
  • stomatitissinusitis
  • dizziness

Mechanism of Action

Imbruvica (ibrutinib) is an orally available, selective inhibitor of Bruton's tyrosine kinase (Btk). Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. BTK’s crole in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion.

Additional Information

For additional information regarding Imbruvica or chronic lymphocytic leukemia/small lymphocytic lymphoma, please visit the Imbruvica web page.