OncoGenex reported results from a randomized Phase 2 study of custirsen in patients with advanced metastatic
castrate resistant prostate cancer, or CRPC. In this study, OncoGenex reported a median overall survival of
23.8 months in patients treated with custirsen plus docetaxel compared to 16.9 months for patients treated with
docetaxel alone. In addition, OncoGenex reported that the unadjusted hazard ratio, a measure used to determine
the difference in survival between treatment groups, was 0.61, representing a 39 percent reduction in the rate of
death for patients treated with custirsen. OncoGenex also reported that patients treated with custirsen in
combination with docetaxel tolerated custirsen well.
OncoGenex has also evaluated custirsen in a Phase 1/2 combination study in patients with NSCLC. In
January 2012, OncoGenex reported that one- and two-year survival rates were 54 percent and 30 percent,
respectively, and 12 percent of patients were still alive at a median follow-up of 41 months. The median overall
survival was 14.1 months and progression-free survival was 4.3 months.
OncoGenex is conducting a global Phase 3 clinical program in patients with CRPC and metastatic NSCLC.
OncoGenex reported results from the Phase 3 SYNERGY study evaluating custirsen as a first-line treatment in
patients with CRPC. OncoGenex reported that treatment with custirsen did not meet the primary endpoint of
statistically significant improvement in overall survival compared to first-line therapy alone (median survival
23.4 months vs. 22.2 months, respectively.) OncoGenex is continuing development of custirsen and has
completed enrollment in the Phase 3AFFINITY study in patients with CRPC and plans to report top-line data
from this study in late 2015/early 2016. OncoGenex is also evaluating custirsen in a Phase 3 clinical study,
ESPIRIT, as a second-line treatment in patients with NSCLC.
Apatorsen
—Apatorsen, formerly OGX-427, is an antisense drug designed to target heat shock protein 27,
or Hsp27, which is a cell survival protein that cells over-produce in response to many cancer treatments,
including hormone ablation therapy, chemotherapy and radiation therapy. Studies have shown that increased
Hsp27 production is prevalent in many human cancers, including prostate, NSCLC, breast, ovarian, bladder,
renal, pancreatic, multiple myeloma and liver cancers. Studies have also linked increased Hsp27 production to
faster rates of cancer progression, treatment resistance and shorter survival duration.
OncoGenex is evaluating apatorsen in patients with cancer. In June 2010, OncoGenex reported results from
a Phase 1 study of apatorsen in patients with a variety of cancers. In this study, patients treated with apatorsen as
a single agent and in combination with docetaxel tolerated the drug well. In addition, apatorsen, when used as a
single agent, demonstrated declines in circulating tumor cells at all doses and in all types of cancer OncoGenex
evaluated. OncoGenex has also reported results from a Phase 1 study in patients with superficial bladder cancer.
In this study, OncoGenex reported that treatment with apatorsen resulted in a trend towards decreased levels of
Hsp27 and increased tumor cell death rates.
OncoGenex has initiated a broad Phase 2 program evaluating apatorsen in seven Phase 2 studies in patients
with cancer. In September 2012, OncoGenex reported preliminary results from a Phase 2 study in patients with
CRPC. In this study, OncoGenex reported that treatment with apatorsen in combination with prednisone resulted
in a higher number of patients without disease progression at 12 weeks and greater declines in prostate-specific
antigen, or PSA, and circulating tumor cells compared to patients treated with prednisone alone.
OncoGenex is evaluating apatorsen in a Phase 2 study, referred to as Borealis-1, in patients with metastatic
bladder cancer in combination with first-line gemcitabine and cisplatin. In December 2014, OncoGenex reported
top-line data from this study showing that treatment at the 600 mg dose correlated with a 14 percent reduction in
risk of death and a 17 percent reduction in progressive disease and death. OncoGenex reported that less benefit
was observed in the 1000 mg cohort due to increased adverse events leading to a higher rate of discontinuation
of both apatorsen and chemotherapy.
OncoGenex is also evaluating apatorsen in these five Phase 2 studies:
•
Borealis-2 is a study in patients with advanced or metastatic bladder cancer in combination with
docetaxel. OncoGenex began enrolling in this study inApril 2013.
•
Pacific is an investigator-sponsored study in combination with Zytiga and prednisone in patients with
metastatic CRPCwho have PSAprogression. Enrollment is estimated to be 80 patients and began in
December 2012.
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