PCI-24781 Presentations at the Upcoming American Association of
Cancer Research (AACR) 100th
Annual Meeting
Pharmacyclics, Inc. (NASDAQ:PCYC) today announced an update to its
clinical programs targeting histone deacetylase (HDAC) with its drug
candidate PCI-24781 that is currently in multiple clinical trials for
treating various solid and hematologic tumors. In addition, the Company
announced multiple presentations regarding its orally available HDAC
inhibitor compound at the annual AACR meeting in Denver, Colorado.
HDAC inhibitors induce differentiation of cancer cells and block cancer
cell proliferation at non-toxic concentrations. PCI-24781 is a novel,
potent, orally active small molecule inhibitor of HDAC enzymes with
anti-tumor activity in a variety of preclinical tumor models (Buggy et
al Mol Cancer Ther 2006; 5 (5), p. 1309-1317) and is synergistic
with many cancer chemotherapeutic agents. PCI-24781 has an optimized
half life, oral bioavailability, potency, and duration of exposure to
achieve an ideal balance of efficacy with minimal toxicity.
In a preliminary data review, PCI-24781 is showing promising response in
ongoing Phase I/II trials in refractory lymphoma and solid tumors, and
is planned to be tested in an upcoming chemotherapy combination setting
trial this summer. Currently 16 patients have been enrolled to date in a
multicenter Phase I/II monotherapy trial in refractory lymphoma. From 10
patients evaluated to date, PCI-24781 has shown good activity (70%
PR+SD) as a single agent, with one partial response in follicular NHL
and verified stable diseases in SLL, CTCL, Hodgkin’s disease and
follicular lymphoma. In addition, one patient with angioimmunoblastic
T-cell lymphoma had a resolution of multiple disease lesions except for
one lesion, but was overall scored as a disease progression. In
refractory solid tumors where 44 patients have been enrolled in IV and
oral dose escalation trials, there were 8 SD out of 31 evaluable
patients. Overall duration of SD was very good, with the longest
duration (8 months) observed in a rectal adenocarcinoma patient. To
date, PCI-24781 has been well tolerated by 60 patients and has
demonstrated an excellent safety profile with no significant
cardiotoxicities or fatigue.
"PCI-24781 is an important HDAC inhibitor which is differentiating
itself in the HDAC competitive space by virtue of lack of serious side
effects such as QTc prolongation and severe fatigue frequently observed
with other HDAC inhibitors.
