Infinity
Pharmaceuticals, Inc. (NASDAQ:INFI) today announced updated data
from a Phase 1 study of IPI-145, its oral inhibitor of
phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in patients with
chronic lymphocytic leukemia (CLL), a potentially fatal hematologic
malignancy (blood cancer). Data from the study showed that IPI-145 was
highly active in patients with relapsed/refractory CLL, with a nodal
response rate of 89 percent and an overall response rate of 48 percent
as defined by the International Workshop on Chronic Lymphocytic Leukemia
(IWCLL) criteria1, including one complete response and 12
partial responses, among patients receiving IPI-145 at doses ≤ 25 mg
twice daily (BID). Onset of activity was rapid, with the majority of
responses occurring in less than two months. These data, along with
safety data showing that IPI-145 was generally well tolerated, support
DUO, Infinity’s Phase 3 registration study of IPI-145 in patients with
relapsed/refractory CLL, which is now enrolling patients.
Additionally, data from this Phase 1 study showed that IPI-145 is active
in other blood cancers, including advanced T-cell lymphomas. Treatment
with IPI-145 in patients with T-cell lymphomas led to an overall
response rate of 38 percent, including one complete response and nine
partial responses. Among the subset of patients with peripheral T-cell
lymphoma (PTCL), IPI-145 led to an overall response rate of 50 percent,
including one complete response and five partial responses. These Phase
1 data in CLL and T-cell lymphoma, as well as in indolent non-Hodgkin
lymphoma (iNHL), were highlighted during the 55th Annual Meeting of the
American Society of Hematology (ASH) press program this morning and will
be presented by Ian Flinn, M.D., Ph.D., director, hematologic
malignancies research, Sarah Cannon Research Institute, and a lead
investigator for the Phase 1 trial, on Monday, December 9, 2013, at 5:30
p.m. CT (6:30 p.m. ET) in Room 295-296 at the Ernest N. Morial
Convention Center in New Orleans, Louisiana.
“The data from this ongoing Phase 1 study of IPI-145 are promising and
show that IPI-145 was clinically active and generally well tolerated in
patients with relapsed/refractory CLL, including a median time to
response of less than two months,” commented Dr. Flinn. “I’m
particularly encouraged by both the complete response and the high nodal
response rate observed in this patient population. Emerging, targeted
therapies such as IPI-145 have the potential to transform the standard
of care for CLL.”
Based on the Phase 1 data reported to date, Infinity is now enrolling
patients in DUO, a Phase 3 study of IPI-145 in patients with CLL. This
randomized study is designed to evaluate the safety and efficacy of
IPI-145 dosed at 25 mg BID compared to ofatumumab in approximately 300
patients with relapsed or refractory CLL. The primary endpoint of the
study is progression-free survival.
IPI-145 Data in Patients with CLL
The presentation, “Preliminary safety and efficacy of IPI-145, a potent
inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with chronic
lymphocytic leukemia” (Abstract #677), included 67 patients evaluable
for safety and 47 evaluable for clinical activity. Among the 67 patients
enrolled in the study, 52 had advanced disease and had progressed during
or were refractory to, intolerant of, or ineligible for established
therapy. An additional 15 treatment-naïve patients were enrolled who
were age 65 or over or high-risk, defined as having 17p deletions or p53
mutations.
Clinical Activity
Updated data from the ongoing Phase 1 study showed that IPI-145 is
clinically active in patients with relapsed/refractory CLL. Treatment
with IPI-145 at doses ≤ 25 mg BID in patients with relapsed/refractory
CLL led to a nodal response rate of 89 percent and an overall response
rate of 48 percent as defined by the International Workshop on Chronic
Lymphocytic Leukemia (IWCLL) criteria1, including one
complete response and 12 partial responses among 27 patients evaluable
for response. The median time to response was less than two months.
Seventy-five percent of patients (six of eight) treated for 12 months or
longer remain progression-free on treatment.
Among 12 patients evaluable with 17p deletions or p53 mutations who
received IPI-145 at doses ≤ 25 mg BID, there were six partial responses,
five patients with stable disease, and one disease progression due to
Richter transformation. Patients with CLL with 17p deletions or p53
mutations generally have a poor response to chemotherapy and worse
prognosis.2
Preliminary data in treatment-naïve patients showed a reduction in
adenopathy in all six patients. Three of these six patients had nodal
responses, including nodal responses in two patients with p53 mutations.
Safety
Data showed that IPI-145 was generally well tolerated, with a safety
profile consistent with co-morbidities seen in patients with advanced
hematologic malignancies. The majority of side effects were low-grade
and/or asymptomatic. The most common ≥ Grade 3 side effects in patients
with relapsed/refractory CLL were neutropenia (30 percent), anemia (12
percent), diarrhea (six percent) and increases in ALT/AST (two liver
enzymes) (six percent). Fewer side effects were observed in
treatment-naïve patients, which is consistent with the co-morbidities of
patients with less advanced disease.
Other Data for IPI-145 Presented at ASH
In
a press release issued yesterday, Infinity reported updated Phase 1
data in patients with iNHL which showed that IPI-145 was clinically
active, with an overall response rate of 73 percent, including three
complete responses, among patients receiving IPI-145 at doses ≤ 25 mg
twice daily (BID). Additionally, translational data showed that IPI-145
effects key signaling molecules in the tumor microenvironment, providing
a potential mechanistic rationale for the clinical activity of IPI-145
observed in patients with iNHL and CLL.
In
a second press release issued yesterday, Infinity reported
preclinical data in models of aggressive non-Hodgkin lymphoma (aNHL) and
T-cell acute lymphoblastic leukemia (T-ALL). Additionally, early Phase 1
clinical data in patients with advanced aNHL were reported, with
reductions in adenopathy (decrease in the size of lymph nodes) observed
in patients with diffuse large B-cell lymphoma (DLBCL) and Richter
transformation, as well as a partial response in a patient with
transformed follicular lymphoma.
Copies of the research presented at ASH will be available in the
Publications Archive on Infinity’s website http://www.infi.com/product-candidates-publications.asp.
About the Development of IPI-145 for the Treatment of Blood Cancers
Infinity is developing IPI-145, an oral inhibitor of Class I
PI3K-delta,gamma. The PI3Ks are a family of enzymes involved in multiple
cellular functions, including cell proliferation and survival, cell
differentiation, cell migration and immunity. The PI3K-delta,gamma
isoforms are preferentially expressed in leukocytes (white blood cells),
where they have distinct and mostly non-overlapping roles in immune cell
development and function. Targeting PI3K-delta and PI3K-gamma may
provide multiple opportunities to develop differentiated therapies for
the treatment of hematologic malignancies as well as inflammatory
diseases.
Infinity has launched DUETTS, a worldwide investigation of IPI-145 in
blood cancers. As part of the DUETTS program, Infinity is currently
enrolling patients in DYNAMO, a Phase 2 monotherapy study designed to
evaluate the safety and efficacy of IPI-145 in patients with refractory
indolent non-Hodgkin lymphoma (iNHL) (ClinicalTrials.gov Identifier
NCT01882803), and DUO, a Phase 3 monotherapy study designed to evaluate
the safety and efficacy of IPI-145 in patients with relapsed/refractory
chronic lymphocytic leukemia (CLL) (NCT02004522).
An investigator-sponsored Phase 1b, open-label study of IPI-145 in
patients with B-cell NHL, CLL and T-cell lymphoma in combination with
rituximab (a monoclonal antibody therapy), bendamustine (a chemotherapy)
or both rituximab and bendamustine is also open for enrollment
(NCT01871675).
Additionally, a Phase 1 study of IPI-145 in patients with advanced blood
cancers is ongoing (NCT01476657).
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative biopharmaceutical company dedicated to
discovering, developing and delivering best-in-class medicines to people
with difficult-to-treat diseases. Infinity combines proven scientific
expertise with a passion for developing novel small molecule drugs that
target emerging disease pathways. For more information on Infinity,
please refer to the company’s website at www.infi.com.
Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of The Private Securities Litigation Reform Act of 1995. Such
forward-looking statements include those regarding the Company’s
expectations about: its ability to execute on its strategic plans; the
therapeutic potential of PI3K inhibition and IPI-145; and the potential
rationale of investigating IPI-145 in additional indications and
combinations therapies. Such statements are subject to numerous
important factors, risks and uncertainties that may cause actual events
or results to differ materially from the company’s current expectations.
For example, there can be no guarantee that Infinity will report data in
the time frames it has estimated, that any product candidate Infinity is
developing will successfully complete necessary preclinical and clinical
development phases, or that development of any of Infinity’s product
candidates will continue. Further, there can be no guarantee that any
positive developments in Infinity’s product portfolio will result in
stock price appreciation. Management’s expectations and, therefore, any
forward-looking statements in this press release could also be affected
by risks and uncertainties relating to a number of other factors,
including the following: Infinity’s results of clinical trials and
preclinical studies, including subsequent analysis of existing data and
new data received from ongoing and future studies; the content and
timing of decisions made by the U.S. FDA and other regulatory
authorities, investigational review boards at clinical trial sites and
publication review bodies; Infinity’s ability to obtain and maintain
requisite regulatory approvals and to enroll patients in its clinical
trials; unplanned cash requirements and expenditures; development of
agents by Infinity’s competitors for diseases in which Infinity is
currently developing or intends to develop its product candidates; and
Infinity’s ability to obtain, maintain and enforce patent and other
intellectual property protection for any product candidates it is
developing. These and other risks which may impact management’s
expectations are described in greater detail under the caption “Risk
Factors” included in Infinity’s quarterly report on Form 10-Q filed with
the Securities and Exchange Commission (SEC) on November 7, 2013, and
other filings filed by Infinity with the SEC. Any forward-looking
statements contained in this press release speak only as of the date
hereof, and Infinity expressly disclaims any obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
1 Halleck M et al. (2008) Guidelines for the diagnosis and
treatment of chronic lymphocytic leukemia: A report from the
International Workshop on Chronic Lymphocytic Leukemia updating the
National Cancer Institute – Working Group 1996 Guidelines. Blood
111: 5446-5456.
2 Grever et al. (2007) Comprehensive assessment of genetic
and molecular features predicting outcome in patients with chronic
lymphocytic leukemia: Results from the US intergroup phase III trial
E2997. J Clin Oncol 25:799-804.
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