Pharmacyclics, Incand Roche earlier today announced that the two companies have entered into a master clinical drug supply agreement designed to evaluate the safety, tolerability and preliminary efficacy ofibrutinib (Imbruvica?;Pharmacyclics), an oral Bruton’s tyrosine kinase (BTK) inhibitor, in combination withobinutuzumab (Gazyva?; Genentech/Roche), a new CD20-directed antibody that attacks targeted cells both directly and together with the body’s immune system, in patients with non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).
CLL is one of the most common forms of blood cancer and in 2014, it is expected that there will be nearly 5,000 deaths from CLL in the United States. Most cases of CLL (95%) start in white blood cells called B-cells that have a protein called CD20 on their surface.
The agreement allows for multiple studies to be considered and conducted. Initially, a Phase III study will be conducted by Pharmacyclics in CLL/SLL. Plans to evaluate the combination for NHL currently are in development. Ibrutinib is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc. [1][2]
…[We’re] evaluating the potential activity of ibrutinib as a single agent and in combination with other agents to determine the benefits that ibrutinib may provide through a variety of uses across several hematologic malignancies…
Both products are approved and marketed for the treatment of CLL. Ibrutinib, a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase or 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. The drug also blocks signals that tell malignant B cells to multiply and spread uncontrollably. Ibrutinib 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.
Obinutuzumab, discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche and, in the United States part of a collaboration between Genentech and Biogen Idec, is used in combination with the chemotherapy drug chlorambucil to treat CLL in patients with previously untreated chronic lymphocytic leukemia. In November 2013 the U.S. Food and Drug Administration (FDA) granted obinutuzumab Breakthrough Therapy Designation due to the significance of the positive progression-free survival (PFS) results from the Phase III CLL11 trial and the serious and life-threatening nature of CLL.
The CLL11 trial, a multicenter, open-label, randomized three-arm study conducted by the German CLL Study Group (GCLLSG), showed that people who received obinutuzumab in combination with chlorambucil chemotherapy had significantly reduced risk of disease progression or death (HR=0.16; p<0.0001) and lived significantly longer without their disease getting worse compared to those who received chlorambucil alone (median PFS 23.0 months vs. 11.1 months).
The use of these two products in combination is investigational only.
“We are committed to evaluating the potential activity of ibrutinibas a single agent and in combination with other agents to determine the benefits that ibrutinibmay provide through a variety of uses across several hematologic malignancies,” noted Bob Duggan, Chairman & CEO, Pharmacyclics. “We look forward to [the opportunity] to evaluate our product with obinutuzumab in order to deliver new treatment options to patients with NHL and CLL.”
The study of the investigational combination of ibrutiniband obinutuzumabthrough several investigator-sponsored trials also is being considered.
For more information:
[1] CLL11: A Study of Obinutuzumab (RO5072759 [GA101]) With Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 1a) [Study Record Detail]
[2] A Multi-Center Study of Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Patients With Treatment na?ve CLL or SLL [Study Record Detail]
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