Onyx Pharmaceuticals Presents Interim Results of Phase 1b Carfilzomib Combination Trial
EMERYVILLE, Calif., June 4 /PRNewswire-FirstCall/ -- Onyx
Pharmaceuticals, Inc. (NASDAQ:ONXX) today announced updated interim
results of the Phase 1b dose-escalation trial, known as the 006
study, evaluating carfilzomib in combination with lenalidomide
(Revlimid®) and low dose dexamethasone in patients with
relapsed and/or refractory myeloma. These data are being presented
today at the 46th American Society of Clinical Oncology (ASCO)
Annual Meeting in Chicago by William Bensinger, M.D., Professor of
Medicine of the Division of Oncology, Fred Hutchinson Cancer
Research Center at the University of Washington School of
Medicine.
The overall response rate in the cohorts of patients receiving
full doses of the combination was 75 percent in 48 evaluable
patients. Median duration of response has not yet been reached. No
dose-limiting toxicities were observed, and the maximum tolerated
dose was not reached. The maximum per-protocol doses of 27mg/m2
carfilzomib, 25mg lenalidomide, and low dose (40mg) dexamethasone
were safely administered. Overall response is measured as a partial
response or greater.(i)
"Nearly all patients with multiple myeloma who receive initial
treatment will eventually relapse and require further therapy,"
said Dr. Bensinger. "Although new agents have been developed over
the past several years, we require additional treatment options
that improve progression-free survival and extend overall response
rates with a tolerability profile that is mild and manageable. The
interim results from this Phase 1b study show an encouraging
efficacy profile in this heavily pretreated group of patients with
myeloma, with no overlapping toxicities with the treatment triplet.
We look forward to further study of this important
carfilzomib-based combination regimen in the upcoming international
Phase 3 trial."
Additional Phase 1b Trial Results
The study was designed to evaluate the safety, maximum tolerated
or maximum per-protocol doses, and efficacy of carfilzomib in
combination with lenalidomide and low-dose dexamethasone. Forty
patients were enrolled in the dose-escalation portion of this study
(cohorts 1-6). Doses were escalated from 15mg/m2 carfilzomib and
10mg lenalidomide to the maximum per-protocol doses of 27 mg/m2
carfilzomib and 25mg lenalidomide. A total of fifty-two patients
received the maximum per-protocol doses, including eight patients
in cohort 6 and forty-four patients in the expansion cohort. All
patients enrolled in the study received 40mg low dose
dexamethasone.
Of the 84 patients in the trial, 79 percent had received more
than two prior treatment regimens for myeloma with 74 percent of
the patients having received prior bortezomib, 87 percent prior
immunomodulatory drug therapy (67 percent prior lenalidomide and 44
percent prior thalidomide), and 98 percent prior steroids.
Side effects were clinically manageable and generally consistent
with those typically seen with the agents that were combined with
carfilzomib. Grade 3/4 adverse events included neutropenia (23
percent), thrombocytopenia (18 percent), anemia (12 percent), and
hyperglycemia (5 percent). The triple combination regimen was well
tolerated and prolonged administration (14-23 months) without
interruption was possible, allowing for durable disease control.
Initial responses typically occurred within the first cycle, with
many patients showing even greater improvement over the subsequent
months while remaining on the initial doses of each agent.
"Based on promising results from this trial, we are planning to
enroll patients in a Phase 3 trial to further evaluate this
three-drug combination therapy in patients with relapsed myeloma,"
said Michael Kauffman, M.D., Ph.D., Chief Medical Officer at Onyx.
"Later this year, we expect to submit a U.S. New Drug Application
filing for carfilzomib as a single agent for relapsed/refractory
myeloma under the accelerated approval mechanism, pending the
top-line results from our Phase 2b trial, known as the 003-A1
study."
About the Carfilzomib Development Program
Carfilzomib is a selective, next-generation proteasome inhibitor
that is being investigated in a broad clinical trial program in
multiple myeloma.
The pivotal Phase 2b monotherapy study, also known as 003-A1,
enrolled patients with relapsed/refractory multiple myeloma.
Top-line results, expected mid-year, may support the filing of a
U.S. New Drug Application (NDA) by year-end 2010.
A European Phase 3 clinical trial of carfilzomib is planned in
relapsed/refractory myeloma and is designed to support a
registrational filing with the EMA. Carfilzomib is also being
evaluated in advanced solid tumors.
About Multiple Myeloma
Multiple myeloma is the second most common hematologic cancer
and results from an abnormality of plasma cells, usually in the
bone marrow. In the U.S., more than 50,000 people are living with
multiple myeloma and approximately 20,000 new cases are diagnosed
annually.(ii) According to estimates by the European Network of
Cancer Registries, there are 21,420 new cases of multiple myeloma
in Europe each year and around 15,000 deaths from this illness. It
is estimated that 60,000 people in Europe are currently living with
this disease.
Worldwide, more than 180,000 people are living with MM and
approximately 86,000 new cases are diagnosed annually.(iii)
About Onyx Pharmaceuticals, Inc.
Onyx Pharmaceuticals, Inc. is a biopharmaceutical company
committed to improving the lives of people with cancer. The
company, in collaboration with Bayer HealthCare Pharmaceuticals,
Inc., is developing and marketing Nexavar® (sorafenib) tablets,
a small molecule drug that is currently approved for the treatment
of liver cancer and advanced kidney cancer. Additionally, Nexavar
is being investigated in several ongoing trials in a variety of
tumor types. Beyond Nexavar, Onyx has established a development
pipeline of anticancer compounds at various stages of clinical
testing, including carfilzomib, a next-generation proteasome
inhibitor, that is currently being evaluated in multiple clinical
trials for the treatment of patients with relapsed or
relapsed/refractory multiple myeloma and solid tumors. ONX 0801, a
targeted alpha-folate inhibitor, and ONX 0912, an oral proteasome
inhibitor, are currently in Phase 1 testing. For more information
about Onyx, visit the company's website at
www.onyx-pharm.com.
Nexavar® (sorafenib) tablets is a registered trademark of
Bayer HealthCare Pharmaceuticals.
Forward-Looking Statements
This news release contains "forward-looking statements" of Onyx
within the meaning of the federal securities laws. These
forward-looking statements include without limitation, statements
regarding the progress and results of the clinical development,
safety, regulatory processes, commercialization efforts or
commercial potential of carfilzomib. These statements are subject
to risks and uncertainties that could cause actual results and
events to differ materially from those anticipated, including risks
related to the development and commercialization of pharmaceutical
products. Any statements contained in this press release that are
not statements of historical fact may be deemed to be
forward-looking statements. Reference should be made to Onyx's
Annual Report on Form 10-K for the year ended December 31, 2009,
filed with the Securities and Exchange Commission under the heading
"Risk Factors" and Onyx's Quarterly Reports on Form 10-Q for a more
detailed description of such factors. Readers are cautioned not to
place undue reliance on these forward-looking statements that speak
only as of the date of this release. Onyx undertakes no obligation
to update publicly any forward-looking statements to reflect new
information, events, or circumstances after the date of this
release except as required by law.
(i) Partial response is defined by > 50% reduction of serum
M-protein and reduction in 24 hour urinary M-protein by > 90% or
to < 200 mg per 24 hours, International Uniform Response
Criteria for Multiple Myeloma Published in Leukemia (2006)
20:1467-1473) with an Erratum in Leukemia (2007)21:1134-1135
(ii) National Cancer Institute, Surveillance Epidemiology and
End Results, 2007 Facts and Figures
(iii) International Agency for Research on Cancer, GLOBOCAN 2002
database
Source: Onyx Pharmaceuticals, Inc.
CONTACT: Investors, Julie Wood, Vice President, Corporate
Communications
& Investor Relations, +1-510-597-6505, or Media, Lori Murray,
Director,
Corporate Communications & Investor Relations, +1-510-597-6394,
both of Onyx
Pharmaceuticals, Inc.
Web Site: http://www.onyx-pharm.com/
Posted: June 2010
