BOTHELL, Wash. and VANCOUVER, British Columbia, May 30, 2015 /PRNewswire/ -- OncoGenex
Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today that results
from a retrospective analysis of the Phase 3 SYNERGY trial showed a
benefit with custirsen therapy in men with metastatic
castrate-resistant prostate cancer (CRPC) who had a poor prognosis.
The analysis, exploring the effect of clusterin inhibition in men
at risk for poor outcomes, showed that over 40 percent of men in
the trial had at least two of five common risk factors for poor
prognosis. In these men, the analysis found a 27 percent
lower risk of death when custirsen was used in combination with
first-line docetaxel compared to docetaxel alone. These results
were presented at the 51st Annual Meeting of the American
Society of Clinical Oncology in Chicago.
"Post-hoc analyses of the SYNERGY trial results provided an
opportunity to explore where custirsen's optimal effect may be in
patients with advanced prostate cancer, particularly those with
risk factors for poor outcomes," said lead study investigator
Kim Chi, M.D., Professor of Medicine
at the Univeristy of British Columbia and Associate Director,
Clinical Research, Vancouver Prostate Centre. "This analysis is
encouraging because custirsen extended survival in a subset of
patients who need new and innovative treatment options once their
disease becomes resistant to initial treatments."
Custirsen is designed to block the production of the protein
clusterin, which is overexpressed in a number of cancers and has
been linked to faster rates of cancer progression, treatment
resistance and shorter survival duration in
patients. OncoGenex, in collaboration with study
investigators, have defined a simple 5-criteria characterization
for poor prognosis in prostate cancer based on the SYNERGY trial,
which include: poor performance status, elevated prostate specific
antigen (PSA), elevated lactate dehyrdogenase (LDH), decreased
hemoglobin, and the presence of liver metastasis. The findings from
the SYNERGY study show a preferential effect in patients who are
more vulnerable to poor outcomes and may reveal the patient
population most likely to benefit from clusterin inhibition in
other studies.
"With these additional analysis from the SYNERGY trial, we
believe we now have criteria for better assessing the patient
population that is most likely to respond to custirsen," said
Scott Cormack, President and CEO of
OncoGenex. "These findings are particularly important because our
ongoing AFFINITY and ENSPIRIT Phase 3 custirsen trials already
include a higher percentage of patients who are at increased risk
for poor outcomes. Evaluating survival specifically in these
high-risk populations will be critical as we move forward with the
custirsen development program."
The Company will be meeting with the U.S. Food and Drug
Administration (FDA) in June to discuss a proposed amendment to the
Phase 3 AFFINITY trial protocol and statistical analysis plan that
would include a co-primary endpoint evaulating survival in men who
are at increased risk for poor outcomes. In the AFFINITY trial,
custirsen is being evaluated with second-line chemotherapy in men
with metastatic CRPC. Results from this trial are expected later
this year or in early 2016.
Custirsen is also being evaluated in the international Phase 3
ENSPIRIT trial of patients with non-small cell lung cancer (NSCLC)
who have progressed following initial treatments. OncoGenex
recently filed an amendment with the FDA and has initiated, or will
be initiating, filings with regulatory agencies in other countries
as it becomes the sponsor in those specific regions to amend the
statistical design and analysis plan to more rigorously and
expediently evaluate the potential survival benefit associated with
custirsen in this aggressive disease. The second and final interim
futility analysis will be conducted in mid-2015 and if passed,
final survival results could be available as soon as the second
half of 2016.
OncoGenex will be hosting a webcast on June 10, 2015 at 9:00 AM
PT / 12:00 PM ET featuring Dr.
Chi to discuss the results from the SYNERGY trial. The
company will also provide an overview of data presented at ASCO
from the Borealis-1 trial evaluating apatorsen in patients with
metastatic bladder cancer. Access to this live event will be
available on the Investor Relations section of the OncoGenex
website at www.OncoGenex.com. Alternatively, the event may be
accessed by dialing (877) 606-1416 (U.S. & Canada) or (707) 287-9313 (International). A
webcast replay will be available approximately two hours after the
call and will be archived on www.OncoGenex.com for 90
days.
About the SYNERGY Trial
The SYNERGY trial evaluated
custirsen plus docetaxel/prednisone compared with
docetaxel/prednisone alone in men with metastatic CRPC
(n=1,022). Following 509 deaths, median overall survival (OS)
was 23.4 months (m) vs. 22.2 m for custirsen and control arms,
respectively (hazard ratio [HR] 0.93; P = 0.42).
In retrospective analyses, a prognostic scoring system was
developed in the control arm using multiple variable modeling and
was used to dichotomize patients into good and poor
prognosis. The analysis included 984 patients with complete
data. Median survival for the poor and good prognosis groups
in the control arm was 14.0 m and 30.4 m, respectively (HR =
3.66).
The custirsen HR effect differed between poor and good prognosis
groups (interaction P = 0.069). The HR estimate for custirsen
survival benefit for those in the poor prognosis group was 0.73
(95% CI: 0.59 to 0.90) and 1.02 (95% CI: 0.76 to 1.37) for those in
the good prognosis. When analyzed separately (n=492), the median OS
in the poor prognostic group was 17.0 m in the custirsen arm vs.
14.0 m in the control arm (HR=0.73, 95%CI: 0.59 to 0.90, P =
0.004).
A more simplified prognostic index score showed that over 40% of
men in the trial had at least two of five common risk factors for
poor prognosis. In these men, the analysis also showed a 27%
lower risk of death when custirsen was used in combination with
first-line docetaxel compared to docetaxel alone.
The adverse events (AEs) observed in the SYNERGY trial were
similar to custirsen's known AE profile. The most
common serious AEs observed in 2 percent of patients treated
with custirsen, beyond those observed in the control arm, included
febrile neutropenia, pneumonia and fever. The most common grade 3
or higher adverse events in 3 percent of patients, whether
classified as good or poor prognosis patients, were neutropenia,
anemia, fatigue and febrile neutropenia.
About Custirsen
Custirsen is an experimental drug that
is designed to block the production of the protein clusterin, which
may play a fundamental role in cancer cell survival and treatment
resistance. Clusterin is upregulated in tumor cells in response to
treatment interventions such as chemotherapy, hormone ablation and
radiation therapy and has been found to be overexpressed in a
number of cancers, including prostate, lung, breast and bladder.
Increased clusterin production has been linked to faster rates of
cancer progression, treatment resistance and shorter survival
duration in patients. By inhibiting clusterin, custirsen is
designed to alter tumor dynamics, slowing tumor growth and
resistance to partner treatments, so that the benefits of therapy,
including survival, may be extended.
Custirsen has Fast Track designation by the FDA for NSCLC and
metastatic CRPC.
About OncoGenex
OncoGenex is a biopharmaceutical
company committed to the development and commercialization of new
therapies that address treatment resistance in cancer patients.
OncoGenex has a diverse oncology pipeline, with each product
candidate having a distinct mechanism of action and representing a
unique opportunity for cancer drug development. Custirsen is
currently in Phase 3 clinical development as a treatment in men
with metastatic castrate-resistant prostate cancer and in patients
with advanced, unresectable non-small cell lung cancer. Apatorsen
is in Phase 2 clinical development and OGX-225 is currently in
pre-clinical development. More information is available at
www.OncoGenex.com and at the company's Twitter account:
https://twitter.com/OncoGenex_IR.
OncoGenex' Forward Looking Statements
This press
release contains forward-looking statements within the meaning of
the "safe harbor" provisions of the Private Securities Litigation
Reform Act of 1995, including, but not limited to, statements
regarding the potential benefits and potential development of our
product candidates and statements regarding our clinical trial
plans and timelines. All statements other than statements of
historical fact are statements that could be deemed forward-looking
statements. These statements are based on management's current
expectations and beliefs and are subject to a number of risks,
uncertainties and assumptions that could cause actual results to
differ materially from those described in the forward-looking
statements. Such forward-looking statements are subject to risks
and uncertainties, including, among others, the risk that our
product candidates do not demonstrate the hypothesized or expected
benefits, the risk of delays in our expected clinical trials, the
risk that the FDA does not approve our proposed amendments to our
clinical trials, the risk that new developments in the rapidly
evolving cancer therapy landscape require changes in our clinical
trial plans or limit the potential benefits of our product, the
risk that our cash resources are insufficient to fund our planned
activities for the time period expected and the other factors
described in our risk factors set forth in our filings with the
Securities and Exchange Commission from time to time, including the
Company's Annual Report on Form 10-K and Quarterly Reports on Form
10-Q. The Company undertakes no obligation to update the
forward-looking statements contained herein or to reflect events or
circumstances occurring after the date hereof, other than as may be
required by applicable law.
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SOURCE OncoGenex Pharmaceuticals, Inc.