LOS ANGELES, Jan. 9, 2014 /PRNewswire/ -- ImmunoCellular
Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) today issued
the following letter to shareholders providing an update on the
Company's ICT-107 clinical program in patients with newly diagnosed
glioblastoma (GBM).
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To Our Shareholders:
Since the December 11, 2013
announcement of results from the exploratory phase II trial of
ICT-107, we have continued to analyze the data set from the trial
and consulted with experts in the field of neuro-oncology with the
goal of informing our next development and regulatory activities
for this program. We would like to update shareholders on three key
topics:
- Our determination that overall survival (OS) was the
appropriate primary endpoint for our development program. Although
we did not meet the OS endpoint, we are enthusiastic about meeting
our progression free survival (PFS) endpoint because we think it
supports the presence of an OS signal, which may clarify, and
potentially strengthen, as we collect more survival data;
- Our review of additional immunological data from the trial. To
date, we have found two hallmark indicators of dendritic cell
activation in the ICT-107 vaccines that are predictive of survival
benefit. This finding is important to developing manufacturing
assays and informing our phase III trial design; and
- Our plan, in the next two to three quarters, to communicate
additional phase II trial data, and to meet with the US FDA and the
European Medicines Agency (EMA) to discuss next steps in the
development of ICT-107.
The primary goals of this exploratory trial were to assess
safety and the effect that ICT-107 has on clinical outcomes in
patients with newly diagnosed GBM, and to gather important insights
that could inform the design of a phase III program. Our intention
is to objectively determine whether ICT-107 can make a meaningful
difference for GBM patients. Based on the top-line results reported
in December we continue to believe that this trial met those goals.
Our current view on the ICT-107 program is positive, and we
anticipate that the additional information we will gather will be
supportive of that view.
Interpreting OS and PFS Results to Date
The phase II trial demonstrated mixed results on the two major
pre-defined clinical endpoints of OS and PFS. The trial met the key
secondary endpoint of demonstrating a statistically significant
treatment benefit for PFS, but missed the primary endpoint of OS,
showing a numerical, but not statistical, advantage of treatment
over placebo. We selected OS as the primary endpoint for clear,
pragmatic reasons: to follow the guidance of the FDA relative to
what constitutes a registration endpoint, and to inform the design
of a phase III registration study. In 2011 written correspondence
with our Company regarding our phase II protocol, the FDA indicated
"…progression free survival (PFS) as an endpoint is acceptable for
hypothesis testing, but not as a primary endpoint for a phase 3
trial to support a BLA." Based on FDA's guidance, we focused the
trial on generating detailed survival data, and retained PFS as an
important secondary clinical endpoint.
Our current view is that PFS matters as an important indicator
of clinical efficacy, but not as an end in itself relative to
registration. In our open-label phase I trial, we observed a PFS
benefit in comparison to historical controls. We were excited by
the important and confirmatory finding in our phase II trial that
ICT-107 improves PFS compared to placebo, as it clearly indicates
that ICT-107 has a positive biological effect in patients and
modulates a clinically important outcome. To our knowledge, ICT-107
is the first immunotherapy in GBM to demonstrate a PFS advantage in
a well-designed, placebo controlled trial, and our clinical
advisors, who are experts in neuro-oncology, have impressed upon us
the importance of this finding.
We think the PFS result could portend improvement in the
ultimate OS result from the phase II trial, and we continue to
collect and incorporate more survival data. Our view is instructed
by two recent publications (K. Han et al, Neuro-Oncology –
December 2013 and M. Polley et al,
Neuro-Oncology – March 2010)
describing analyses of glioblastoma trials which establish a strong
correlation between PFS and OS hazard ratios. As a reminder, we do
not yet have final median survival times from the trial, but
anticipate reaching them within the first half of 2014. The
median survival times reported in December were estimates based on
67 events out of a possible 124 events, with an average follow-up
time of about 14.2 months from randomization.
Importance of Immunological Data
In addition to learning more about the OS and PFS results and
the relationship between them, we believe that there are three
categories of immunological data that have the potential to further
inform our phase III planning.
- First, we have patient tumor samples being analyzed for antigen
expression. ICT-107 is a dendritic cell vaccine incorporating six
antigens from tumor and cancer stem cells. In the small phase
I trial, we demonstrated a correlation between the expression of
certain antigens in patients' tumors and OS and PFS. We expect the
phase II tumor expression data to be available in the second
quarter of 2014, and we plan to look for a corresponding
relationship in this much larger data set.
- Second, we have detailed dendritic cell characterization data
from all of the vaccines prior to administration. We have
identified two hallmark indicators of dendritic cell activation
that are statistically predictive of OS in the treated
patients. This important finding may inform both
manufacturing assay development and phase III trial
design.
- Third, we collected blood samples throughout the trial which we
are analyzing for vaccine-induced T-cell activation. We expect
these results to become available in the second quarter of 2014,
and should enable us to determine if there is a relationship
between vaccine responders and OS.
Collectively, these immunological data will inform our phase III
design and how we might target patient selection.
Next Steps in Phase III Planning
In the next few weeks, we will submit an abstract for the
50th Anniversary Annual ASCO meeting taking place
May 30-June 3, 2014. If the
abstract is accepted, we will report on more mature OS results and
findings from the immunological analysis.
Subsequent to ASCO, we plan to meet with FDA for an end-of-phase
II discussion of the ICT-107 trial results and future trial design.
We anticipate this meeting can take place late in the second
quarter or in the third quarter of 2014. After that meeting, we
will be in a better position to evaluate what next steps might be
required to plan a phase III trial for ICT-107. The timing to begin
a potential next clinical trial is not certain at this time, but a
reasonable timeframe could be late 2014 or early 2015.
In the second quarter, we expect to have a decision from the
European Medicines Agency or EMA on granting ICT-107 orphan
designation in the EU (we already have orphan designation in the
US), and we are planning for our first in-person discussion with
the EMA regarding ICT-107 clinical data also in the second quarter.
The management and board of ImmunoCellular want to thank our
shareholders for your continued support and interest. We will look
forward to keeping you informed as our plans and strategies for
ICT-107, as well as our other pipeline programs and corporate
initiatives, take shape.
About ImmunoCellular Therapeutics, Ltd.
ImmunoCellular Therapeutics, Ltd. is a Los Angeles area-based clinical-stage company
that is developing immune-based therapies for the treatment of
brain and other cancers. ImmunoCellular has concluded a phase II
trial of its lead product candidate, ICT-107, a dendritic
cell-based vaccine targeting multiple tumor-associated antigens for
glioblastoma. ImmunoCellular's pipeline also includes ICT-121, a
dendritic cell vaccine targeting CD133, and ICT-140, a dendritic
cell vaccine targeting ovarian cancer antigens and cancer stem
cells. To learn more about ImmunoCellular, please visit
www.imuc.com.
Forward-Looking Statements for ImmunoCellular Therapeutics
This press release contains certain forward-looking statements
that are subject to a number of risks and uncertainties, including
the risk that ICT-107 can be further successfully developed or
commercialized, the outcome and timing of our immunological data,
the outcome of our end of phase II meeting with the FDA, and our
ability to show that PFS and OS outcomes are related with respect
to ICT-107 in a manner that justifies further development.
Additional risks and uncertainties are described in IMUC's most
recently filed quarterly report on Form 10-Q and annual
report on Form 10-K. Except as permitted by law, IMUC undertakes no
obligation to update or revise any forward-looking statements,
whether as a result of new information, future events or
otherwise.
Contact:
ImmunoCellular Therapeutics, Ltd.
Investor Relations
Jane Green
415.348.0010 direct
415.652.4819 mobile
jane@jmgcomm.com
SOURCE ImmunoCellular Therapeutics, Ltd.