SAN DIEGO, Dec. 2, 2018 /PRNewswire/ -- MEI Pharma,
Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on
advancing new therapies for cancer, today announced that results
from an ongoing Phase 1b study
support the complementary potential of intermittent and continuous
dosing schedules of ME-401, a selective phosphatidylinositol
3-kinase ("PI3K") delta inhibitor, to optimize the clinical
risk-benefit ratio in patients with relapsed/refractory follicular
lymphoma. The data demonstrate that ME-401, as both a single agent
and in combination with rituximab, continues to be associated with
overall high objective response rates. In addition, low rates of
Grade 3 immune-related adverse events (irAEs) were observed in
patients on the intermittent dosing schedule while maintaining a
high level of clinical response. These data are being presented
today at the 2018 American Society of Hematology (ASH) Annual
Meeting.
The data announced today continue to support the rationale for
MEI's planned Phase 2 study that evaluates both a continuous (CS)
and intermittent (IS) dosing schedule of ME-401 as a means to
enhance the drug candidate's clinical profile and thus potentially
deliver improved benefits to patients. The Phase 2 study is
expected to start around year-end and is intended to support MEI's
accelerated approval registration strategy if successful.
Patients in the Phase 1b study
received ME-401 as a single agent (dosed on the CS or IS) and in
combination with rituximab (dosed on the IS only) to explore
treatment options for patients with B-cell malignancies. The IS
dosing regimen consists of 60 mg given continuously, once-daily,
for the first 2 cycles followed by 60 mg given on days 1-7 of a
28-day cycle and results showed:
- As a single agent, 76% objective response rate in patients with
relapsed or refractory follicular lymphoma (FL), and 100% in all
patients with chronic lymphocytic lymphoma (CLL) and small
lymphocytic lymphoma (SLL).
-
- In combination with rituximab, 78% objective response rate in
patients with FL.
- Median duration of response has not been reached. The lead
patient has a duration of response of approximately 20 months and
the median follow-up is 9.3 months.
- Low rate of irAEs; 4 irAEs were reported in 36 patients
administered the IS, with all cases occurring in the first 2 cycles
following the switch to IS.
- 89% of patients switched to IS remain on therapy.
-
- Disease control was maintained in 72% of these patients.
- 70% of patients who resumed on the continuous daily dosing
schedule (CS) recaptured a response after progressing on IS.
The ME-401 ASH 2018 poster can be accessed on the MEI Pharma
website.
"The data presented today are very supportive of our rationale
to investigate both a continuous and intermittent dosing regimen as
part of our Phase 2 study evaluating ME-401 in follicular lymphoma
and may also help advance its complementary potential to deliver
improved benefits to patients in combination with other
modalities," said Daniel P. Gold, Ph.D., president and chief
executive officer of MEI Pharma. "While advances have been made in
the treatment of B-cell malignancies, there remains a significant
need for innovative therapies across a range of indications and
patient populations not addressed by current therapeutic options;
we believe the emerging clinical profile of ME-401, as both a
single agent or in combination, holds the potential to deliver
improved clinical benefit to patients with B-cell diseases."
ME-401 Phase 1b ASH 2018
Data
ME-401 is being evaluated in an ongoing Phase
1b dose escalation study in patients
with relapsed or refractory B-cell malignancies. Through
October 2018, 60 patients were
enrolled across three groups:
- Group 1 included 31 patients with relapsed FL (n = 22) or
CLL/SLL (n = 9) who received ME-401 CS at doses ≥60 mg per day in
the dose escalation phase of the study. Beginning in December 2017 a total of 17 patients from Group 1
(FL=9, CLL/SLL=8) advanced to the IS after in cycle 4 or later
cycles.
- Group 2 included 16 patients with relapsed FL (n = 9), diffuse
large B-cell lymphoma (n = 5), marginal zone lymphoma (MZL, n = 1),
and CLL (n = 1) who received rituximab 375 mg/m2 x 8
doses over 6 months and ME-401 dosed under the IS regimen after
receiving ME-401 60 mg daily for the first two cycles.
- Group 3 may enroll up to 30 patients with relapsed FL/CLL/SLL
in an expansion cohort of ME-401 using the IS regimen after
receiving ME-401 60 mg daily for the first two cycles. In this
group, 13 patients were enrolled to date with one FL patient
reaching the Cycle 6 disease assessment as data cut off.
The median number of prior therapies of patients in the study is
two and 50% of patients enrolled were ≥ 3rd line of
therapy. Responses are assessed after 2 cycles (58 days) and 6
cycles, and then every 6 cycles. Ninety-two percent of all patients
were previously treated with an anti-CD20 antibody.
Objective Response Rates
- The objective response rate of patients across all groups with
FL is 76% (29/38) and for CLL/SLL is 100% (11/11).
-
- As a single agent, 76% (22/29) objective response rate in
patients with FL and 100% (10/10) in patients with CLL and
SLL.
- In combination with rituximab, 78% (7/9) objective response
rate in patients with FL.
Duration of Response
- In FL and CLL/SLL patients, the median follow-up is 9.3 months
(range, approximately 2.1 to 19.5 months) with no median yet
reached.
- Across all groups, failure-free survival (i.e. no disease
progression on the continuous dosing schedule) in FL and CLL/SLL
has not reached a median yet; median follow-up is 6.9 months (range
0.4 to 21.1 months).
- 72% of patients across all groups on the IS regimen have not
experienced disease progression with a median follow-up of 7.9
months (range, 0.8 to 10.5 months).
-
- Of the 10 patients that progressed on the IS regimen, 70% of
patients retreated with daily dosing recaptured disease
response.
Rates of irAEs
- Of the 36 patients who switched to IS, only 11% (4/36)
experienced an irAE after the switch. All 4 reported cases of irAEs
occurred in the first 2 cycles after the switch to the IS
regimen.
About ME-401
ME-401 is an investigational oral phosphatidylinositol 3-kinase
("PI3K") delta inhibitor; PI3K delta is often overexpressed in
cancer cells and plays a key role in the proliferation and survival
of hematologic cancer cells. ME-401 displays high selectivity for
the PI3K delta isoform and has distinct pharmaceutical properties
from other PI3K delta inhibitors. It is being clinically evaluated
in patients with various B-cell malignancies. MEI is initiating a
Phase 2 study to evaluate the efficacy, safety, and tolerability of
ME-401 as a single agent in patients with follicular lymphoma after
failure of at least two prior systemic therapies including
chemotherapy and an anti-CD20 antibody. The Phase 2 study is
intended to support an accelerated approval marketing application
with the U.S. Food and Drug Administration.
About MEI Pharma
MEI Pharma, Inc. (Nasdaq: MEIP) is
a San Diego-based pharmaceutical company focused on leveraging
its extensive development and oncology expertise to identify and
advance new therapies for cancer. The Company's portfolio of drug
candidates includes pracinostat, an oral HDAC inhibitor that is
partnered with Helsinn Healthcare, SA. Pracinostat has been granted
Breakthrough Therapy Designation from the U.S. Food and Drug
Administration for use in combination with azacitidine for the
treatment of patients with newly diagnosed acute myeloid leukemia
(AML) who are unfit for intensive chemotherapy. Pracinostat is also
being developed in combination with azacitidine for the treatment
of patients with high and very high-risk myelodysplastic syndrome
(MDS). MEI Pharma's clinical development pipeline also includes
ME-401, a highly differentiated oral PI3K delta inhibitor currently
in a Phase 1b study in patients with relapsed refractory
follicular lymphoma or CLL, and voruciclib, an oral, selective CDK
inhibitor shown to suppress MCL1, a known mechanism of resistance
to BCL2 inhibitors. The Company is also developing ME-344, a novel
mitochondrial inhibitor currently in an investigator-initiated
study in combination with bevacizumab evaluating patients with
HER2-negative breast cancer. Pracinostat, ME-401, ME-344 and
voruciclib are investigational agents and are not approved for use
in the U.S. For more information, please
visit www.meipharma.com.
Under U.S. law, a new drug cannot be marketed until it has
been investigated in clinical studies and approved by the FDA as
being safe and effective for the intended use. Statements included
in this press release that are not historical in nature are
"forward-looking statements" within the meaning of the "safe
harbor" provisions of the Private Securities Litigation Reform Act
of 1995. You should be aware that our actual results could differ
materially from those contained in the forward-looking statements,
which are based on management's current expectations and are
subject to a number of risks and uncertainties, including, but not
limited to, our failure to successfully commercialize our product
candidates; costs and delays in the development and/or FDA
approval, or the failure to obtain such approval, of our product
candidates; uncertainties or differences in interpretation in
clinical trial results; our inability to maintain or enter into,
and the risks resulting from our dependence upon, collaboration or
contractual arrangements necessary for the development,
manufacture, commercialization, marketing, sales and distribution
of any products; competitive factors; our inability to protect our
patents or proprietary rights and obtain necessary rights to third
party patents and intellectual property to operate our business;
our inability to operate our business without infringing the
patents and proprietary rights of others; general economic
conditions; the failure of any products to gain market acceptance;
our inability to obtain any additional required financing;
technological changes; government regulation; changes in industry
practice; and one-time events. We do not intend to update any of
these factors or to publicly announce the results of any revisions
to these forward-looking statements.
View original content to download
multimedia:http://www.prnewswire.com/news-releases/mei-pharma-presents-clinical-data-from-ongoing-phase-1b-study-of-me-401-in-patients-with-indolent-b-cell-malignancies-at-the-2018-american-society-of-hematology-annual-meeting-300758635.html
SOURCE MEI Pharma, Inc.