Follow-up Results of Phase 2 Study of Investigational Agent, Ibrutinib, Suggest High and Durable Responses in Relapsed/Refractory Mantle Cell Lymphoma
ATLANTA, Dec. 11, 2012 /PRNewswire/ -- Pharmacyclics, Inc. (PCYC) today announced follow-up findings from an ongoing, open-label, Phase 2, single-agent study suggesting that in patients with relapsed or refractory mantle cell lymphoma (MCL), both those who were bortezomib-naive and bortezomib-exposed, the investigational oral agent ibrutinib (PCI-32765) resulted in high and durable responses and was generally well tolerated. In the study, 111 patients received ibrutinib and 110 were evaluable for efficacy. The median follow-up time was 9.2 months, with a range of time to response to treatment of 1.4 to 16.4 months.
The results were presented by lead investigator Michael L. Wang, M.D., associate professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, at the 54th Annual Meeting of the American Society of Hematology (ASH) in Atlanta, Ga. The study showed an overall response rate (ORR) of 68 percent, including a complete response (CR) of 22 percent and a partial response (PR) of 46 percent with a median progression free survival (PFS) estimated at 13.9 months. Results were similar between the bortezomib-naive and bortezomib-exposed patients.
Long-term follow up of the initial 51 patients enrolled in this study that were presented last year at ASH shows there was an incremental improvement in the response rate over time. The ORR increased for this patient subset from 69 percent in 2011 to an ORR of 75 percent in 2012, with the CR increasing from 16 percent to 39 percent over the same period.
"Now with a larger number of patients studied, we see the overall response rate remains durable and the safety profile continues to appear manageable," said Dr. Wang. "In addition, what is particularly encouraging is that with longer follow-up there is an incremental increase in the number of patients who achieve complete response."
Relapsed MCL means the disease has returned after an initial partial or total remission. Refractory MCL refers to cancer that does not respond to current treatment.
Safety data were available for 111 patients in the trial. Patients treated with ibrutinib experienced treatment-emergent adverse events (AEs) that were consistent with previously reported data. Treatment-emergent AEs were mainly grade 1 or 2. Treatment-emergent AEs of all grades occurring in 20 percent or more patients were diarrhea, fatigue, nausea, upper respiratory tract infection and dyspnea (shortness of breath). Pneumonia was the only grade 3 or higher treatment-emergent AE occurring in 5 percent or more patients.
"These results are encouraging because they suggest ibrutinib provided a durable response in the treatment of mantle cell lymphoma in this Phase 2 study," said Bob Duggan, CEO and Chairman of the Board of Directors of Pharmacyclics. "Pharmacyclics' overall mission is to improve the quality and duration of life for oncology patients."
PCYC-1104-CA is an international, multicenter, open-label, Phase 2, single-agent study that treated 111 relapsed or refractory patients (63 bortezomib-naive and 48 bortezomib-exposed) with oral ibrutinib 560 mg daily for continuous dosing until disease progression. The primary endpoint of the study is ORR. Duration of response and safety evaluation are important secondary endpoints.
About Mantle Cell Lymphoma
MCL is an aggressive type of B-cell non-Hodgkin lymphoma (NHL) that usually occurs in middle-aged or older adults. The disease typically begins in the lymph nodes but can spread to other tissues, such as bone marrow and liver. In the United States, there are approximately 70,130 new cases of NHL and 4,600 new cases of MCL each year.
Ibrutinib was designed to specifically target and selectively inhibit an enzyme called Bruton's tyrosine kinase (BTK). BTK is a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel regulating B-cell apoptosis, cell adhesion, and lymphocyte migration and homing. Data are consistent with a mechanistic model whereby ibrutinib blocks BCR signaling, which drives cells into apoptosis and/or disrupts cell migration and adherence to tumor-protective microenvironments.
The effectiveness of ibrutinib alone or in combination with other treatments is being studied in several B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma, relapsed/refractory mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma and multiple myeloma. A comprehensive late-stage Phase 2 and 3 program is under way.
Conference Call and Webcast Details
Pharmacyclics will be holding a conference call on Wednesday, December 12, 2012 at 8:30 AM ET. To participate in the conference call, please dial 1-877-407-0778 for domestic callers and 1-201-689-8565 for international callers. To access the live audio broadcast or the subsequent archived recording, log on to http://ir.pharmacyclics.com/events.cfm. The archived version of the webcast will be available for 30 days on the Investor Relations section of the company's website at www.pharmacyclics.com.
About the Pharmacyclics and Janssen Collaboration
Pharmacyclics, Inc. and Janssen Biotech, Inc. entered into a worldwide collaboration on December 8, 2011, to develop and commercialize ibrutinib. Following regulatory approval, Pharmacyclics and Janssen will co-commercialize ibrutinib. Each company will lead development for specific indications as stipulated in a global development plan.
Pharmacyclics ® is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative small-molecule drugs for the treatment of cancer and immune mediated diseases. Our mission and goal is to build a viable biopharmaceutical company that designs, develops and commercializes novel therapies intended to improve quality of life, increase duration of life and resolve serious unmet medial healthcare needs; and to identify promising product candidates based on scientific development and administrational expertise, develop our products in a rapid, cost-efficient manner and pursue commercialization and/or development partners when and where appropriate.
Presently, Pharmacyclics has three product candidates in clinical development and several preclinical molecules in lead optimization. We are committed to high standards of ethics, scientific rigor, and operational efficiency as we move each of these programs to viable commercialization.
The Company is headquartered in Sunnyvale, California and is listed on NASDAQ under the symbol PCYC. To learn more about how Pharmacyclics advances science to improve human healthcare visit us at http://www.pharmacyclics.com.
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Note: Data in this release correspond to ASH Abstract 904.
SOURCE Pharmacyclics, Inc.