Date: 2014-10-16
Type of information: Clinical research agreement
Compound: Imbruvica® (ibrutinib) and Gazyva® (obinutuzumab)
Company: Pharmacyclics (USA - CA) Roche (Switzerland)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: tyrosine kinase inhibitor/Bruton's tyrosine kinase inhibitor/monoclonal antibody. Imbruvica® (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton's tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells. Imbruvica® blocks signals that tell malignant B cells to multiply and spread uncontrollably. Gazyva® (obinutuzumab) is a glycoengineered, fully humanized IgG1 monoclonal antibody with potential antineoplastic activity. Obinutuzumab, a third generation type II anti-CD20 antibody, selectivity binds to the extracellular domain of the human CD20 antigen on malignant human B cells. The Fc region carbohydrates of the antibody, enriched in bisected non-fucosylated glycosylation variants, contribute to its higher binding affinity for human FcgammaRIII receptors compared to non-glycoengineered antibodies, resulting in enhanced antibody-dependent cellular cytotoxicity (ADCC) and caspase-independent apoptosis. In addition, modification of elbow hinge sequences within the antibody variable framework regions may account for the strong apoptosis-inducing activity of R7159 upon binding to CD20 on target cells. Preclinical studies demonstrate that GA101 induces significant B-cell depletion in peripheral blood as well as in lymphoid tissue. It also mediates high antitumor activity in preclinical NHL studies, both as a single agent and in conjunction with chemotherapy. Genentech is investigating this agent with Biogen Idec.
Imbruvica® is approved for the treatment of patients with Chronic Lymphocytic Leukemia (CLL) who have received at least one prior therapy, and for the treatment of CLL patients with del 17p, a genetic mutation that occurs when part of chromosome 17 has been lost. Imbruvica® is also approved for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
Disease: non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Details: * On October 16, 2014, Pharmacyclics announced that it has entered into a master clinical drug supply agreement with Roche to evaluate the safety, tolerability and preliminary efficacy of Imbruvica® (ibrutinib) in combination with Gazyva® (obinutuzumab) in patients with non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). The agreement allows for multiple studies to be considered and conducted. Initially, a Phase 3 study will be conducted by Pharmacyclics in CLL/SLL. Plans to evaluate the combination for NHL currently are in development. Imbruvica® is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc. Both products are approved and marketed for the treatment of CLL. Imbruvica® is used to treat CLL in patients who have received one prior therapy, and in CLL patients with deletion of the short arm of chromosome 17 (del 17p CLL), including treatment naive and previously treated del 17p CLL patients. Gazyva® is used with the chemotherapy drug, chlorambucil, to treat CLL in patients with previously untreated chronic lymphocytic leukemia. The use of these products in combination is investigational only.
"We are committed to evaluating the potential activity of Imbruvica® as a single agent and in combination with other agents to determine the benefits that IMBRUVICA may provide through a variety of uses across several hematologic malignancies," said Bob Duggan, Chairman & CEO, Pharmacyclics. "We look forward to a rewarding and productive partnership with Roche to evaluate our product with GAZYVA in order to deliver new treatment options to patients with NHL and CLL."
The study of the investigational combination of Imbruvica® and Gazyva® through several investigator-sponsored trials also is being considered. Additional details of the agreement were not disclosed.
Financial terms:
Latest news:
