Data Results from the Phase IB/II Study in CLL/SLL as presented at ASCO
The oral presentation, titled "Activity and tolerability of the Bruton's tyrosine kinase (Btk) inhibitor PCI-32765 in patients with chronic lymphocytic leukemia/small cell lymphocytic lymphoma (CLL/SLL): Interim results of a Phase Ib/II study" was being presented by
Overall, PCI-32765 has been well-tolerated; discontinuation of treatment for adverse events occurred in only 3 of 83 patients. Diarrhea, nausea/ vomiting, and dyspepsia were the most frequently reported events and were typically of modest severity. Significant neutropenia and thrombocytopenia were uncommon in the 420mg qD cohorts, but more frequently observed (18%, 9% respectively) in the 840mg qD cohort in spite of the shorter follow-up. As previously reported, a characteristic pattern of response occurred in the CLL patients, with rapid reduction of lymph node disease and a corresponding initial phase of lymphocytosis. The resolution of lymphocytosis was more rapid in treatment-naive versus relapsed/ refractory patients, corresponding to a more rapid evolution of overall response per standard criteria in treatment-naive patients. At a median follow-up of 6.3 months, 67% of patients with treatment-naive disease had achieved an overall response by standard criteria, with an additional 19% of patients achieving a nodal response. At a median follow-up of 7.8 months in the cohort of relapsed/ refractory patients treated with 420mg qD, the rate of overall objective response was 48% with an additional 41% of patients having achieved a nodal response. The initial response assessment at 2 months in patients with relapsed/ refractory disease appeared similar between the 420mg qD and 840mg qD doses. Additionally, achieving response appeared to be independent of poor-risk features, such as del (17p), del (11q), and lack of mutation in the immunoglobulin heavy chain variable region gene. To date, only three patients have experienced disease progression, and 81% of relapsed/ refractory patients in the more mature 420mg qD cohort are on treatment and free-of-progression at 6 months.
Update and Highlights of the PCI-32765 Clinical Development Program
Phase IA Study in B-Cell Malignancies - Updated Results
The previously reported Phase IA trial of PCI-32765 in patients with relapsed or refractory B-cell malignancies was updated. No significant changes in the safety profile have emerged with longer follow-up of this trial. Low-grade diarrhea, fatigue, cough, nausea, and headache were the most frequently reported adverse events; significant neutropenia and thrombocytopenia were uncommon. With longer follow-up, the objective response rate in evaluable patients with CLL/SLL (now 11/14, 79%) and follicular lymphoma (now 6/13, 46%) improved as compared to
Broad Clinical Development Progress for Btk Inhibitor PCI-32765 in B-cell Malignancies
Throughout 2011 we will continue to execute this clinical trials program, and will analyze data from these trials on an ongoing basis. Below is an update on each of our current PCI-32765 clinical development programs.
-- Chronic Lymphocytic Leukemia / Small Cell Lymphocytic Lymphoma (CLL/SLL)
Our CLL/SLL program has enrolled 137 patients through
Two ongoing studies, initiated in Q1 2011, are evaluating PCI-32765 in combination with standard therapies for CLL/SLL. We have enrolled 34 patients in these studies and anticipate completing enrollment in 2011.
From these studies, we expect to be able to analyze initial 3-month safety data for ofatumumab/PCI-32765 and bendamustine/rituximab/PCI-32765 in the second half of 2011. To date the preliminary safety data from these combination studies suggests that these combinations are likely to be safe.
Based on the significant single-agent activity in CLL/SLL from the ongoing Phase IB/II trial, and contingent upon confirmation of 3-month combination safety data, Phase III planning is currently underway. We expect to initiate a Phase III study in CLL/ SLL in the first half of 2012.
-- Mantle Cell Lymphoma (MCL)
A Phase II study of single-agent PCI-32765 in relapsed or refractory MCL (PCYC-1104) began enrolling patients in late
-- Diffuse Large B-Cell Lymphoma (DLBCL)
A multicenter, open-label, Phase II study of PCI-32765 in patients with relapsed or refractory DLBCL (PCYC-1106) began enrollment in
A separate pilot study of PCI-32765 in patients with
-- Follicular Lymphoma (FL)
Updated results from the Phase IA study have shown an improvement in the objective response rate in follicular lymphoma. We are encouraged by this preliminary signal and are developing a Phase II program in this histology. We anticipate the initiation of a Phase II trial in follicular lymphoma in the first half of 2012.
-- Multiple Myeloma (MM)
Ongoing pre-clinical studies, both internally as well as through external collaborations, have suggested a vital role for Btk in both malignant plasma cells and osteoclasts, which are involved in the bone complications of this disease. Therefore, we believe that Btk represents a viable therapeutic target in MM, and we are developing a Phase II trial of PCI-32765 in MM, which we expect to initiate in early 2012.
ASCO Conference Call and Webcast Details
Slides used in the ASCO presentation from today and during the conference call are posted on the Investor Relations Section of our website, under Events & Webcasts: http://ir.pharmacyclics.com/events.cfm
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 Web site at www.pharmacyclics.com.
Large unmet needs in Non-Hodgkin's Lymphoma (NHL) Market
There are over 25 distinct subtypes of B-cell malignancies; the common NHLs include the following: follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma and mantle cell lymphoma. The
There are significant and distinct areas of unmet medical need across the
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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 expertise, develop our products in a rapid, cost-efficient manner and pursue commercialization and/or development partners when and where appropriate.
The Company is headquartered in
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