Clinical data of PCI-32765 in patients with CLL presented at ASH Annual Meeting

Pharmacyclics, Inc. (Nasdaq: PCYC) today announced data from three Chronic Lymphocytic Leukemia (CLL) presentations at the American Society of Hematology (ASH) Annual Meeting describing the Btk-selective inhibitor PCI-32765.  Two presentations report preclinical data, and one presentation reports clinical data from a pooled analysis of 54 patients with CLL or Small Lymphocytic Lymphoma (SLL) treated with PCI-32765.

The two preclinical abstracts focus on the mechanism of action of this novel drug.  An oral presentation titled "Bruton's Tyrosine Kinase Inhibitor PCI-32765 Abrogates BCR and Nurselike Cell-Derived Activation of CLL Cells In Vitro and In Vivo" is being presented by Sabine Ponader, PhD from the MD Anderson Cancer Center.  The other preclinical presentation is a poster presented by Sarah Herman, PhD of the laboratory of John Byrd, MD, of The Ohio State University titled "The Kinase Inhibitor, PCI-32765, Demonstrates Activity in Chronic Lymphocytic Leukemia Cells Independent of Microenvironmental Survival Signals." Data from these two presentations together suggest a model whereby PCI-32765 directly affects CLL cells by inducing apoptosis, and also blocks the ability of CLL cells to migrate to and to adhere to lymph nodes, a protective environment where the tumors grow. The clinical results of treatment, as discussed below, appear to bear out these combined mechanisms, with evidence of impairment of both homing to lymph nodes and cell viability in the typical clinical response to PCI-32765.

Data Results from the Pooled Phase IA and IB Studies in CLL/SLL

The oral presentation, titled "The Bruton's Tyrosine Kinase Inhibitor PCI-32765 is Well Tolerated and Demonstrates Promising Clinical Activity In Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): An Update on Ongoing Phase 1 Studies" is being presented by Jan Burger MD, PhD. This abstract describes clinical data from a pooled analysis of 54 CLL/SLL patients from a Phase Ia>

Response data from the pooled analysis is presented below.  Outcomes are described based on strict application of standard response criteria, with an additional outcome category termed "nodal response with lymphocytosis." This category describes patients with substantial lymph node (LN) shrinkage who have not yet achieved a 50% decrease of malignant B cells in the blood (lymphocytosis). The inclusion of this category is necessary because of the unique characteristics of response to this agent, especially early in treatment.  From the Ia trial, with approximately 8 months median follow-up, 1 patient achieved a complete response (CR) and 8/13 evaluable patients achieved a partial response (PR) for an objective response rate of 69%. Two additional patients achieved a nodal response with lymphocytosis (15%) and 2 patients had stable disease (SD).  Of note, 3 of the patients now classified as partial responses were initially nodal response with lymphocytosis earlier in treatment. In the Ib/II trial, with less than 2 months median follow-up, 8/32 evaluable patients achieved a PR (25%) by standard response criteria with an additional 17/32 (53%) achieving a nodal response with lymphocytosis.  Six other patients have SD. As noted previously, study of the patients from the Ia trial suggest that blood lymphocytosis decreases over time on treatment and patients who initially are described as nodal responses with lymphocytosis may achieve a PR by standard response criteria with continued therapy.

Based on the pooled analysis from the Phase Ia study (~8 months median follow-up) and the Ib/II study (<2 months median follow-up) in this group of CLL/SLL patients, of the 45 evaluable patients, one patient achieved a CR (2%), 16 (36%) achieved a PR and an additional 19 (42%) have experienced a dramatic reduction in lymph node disease with lymphocytosis. When evaluating nodal disease alone, 87% percent (34 out of 39) of patients achieved a 50% or greater reduction in lymph node burden.  In patients with symptomatic disease, this early response was often associated with improvement in symptoms.

PCI-32765 continues to be well tolerated in this patient population.  Grade 3/4 events were uncommon. More common grade1/2 events were diarrhea and other GI and constitutional symptoms.  No hepatic or renal laboratory adverse events were reported on this trial and significant hematologic events were infrequent. There was no evidence of cumulative toxicity.

SOURCE Pharmacyclics