Carfilzomib Data Demonstrate Promising Efficacy and Tolerability Signals in Ongoing Phase 1b/2 Combination Study with Lenalidomi
08 December 2009 - 12:01AM
PR Newswire (US)
Phase 3 Combination Trial Planned for 2010 NEW ORLEANS, Dec. 7
/PRNewswire-FirstCall/ -- Onyx Pharmaceuticals, Inc. (NASDAQ:ONXX)
today announced interim results from the Phase 1b/2 006 study,
demonstrating that carfilzomib, when administered with the standard
therapies lenalidomide (Revlimid®) and low dose dexamethasone, is
active and well-tolerated in patients with relapsed and/or
refractory multiple myeloma. These data were presented at the 51st
annual meeting of the American Society of Hematology (ASH) in New
Orleans. A large, randomized international Phase 3 clinical trial
studying the combination of lenalidomide and low dose dexamethasone
with or without carfilzomib is planned for 2010. "In many cases,
responses were rapid and continued to improve with prolonged
treatment, suggesting the combination may be appropriate for early
disease control followed by chronic management of relapsed
myeloma," said lead investigator Ruben Niesvizky, M.D., director of
the Multiple Myeloma Service at the Center of Excellence for
Lymphoma and Myeloma at New York Presbyterian Hospital-Cornell
Medical Center. "Preliminary results from this study show no
overlapping toxicities between carfilzomib and the lenalidomide and
low dose dexamethasone combination. As a result, we were able to
safely administer carfilzomib and lenalidomide at full doses for
longer than ten months in some cases, despite the relapsed and
often refractory status of disease in our patients. We look forward
to further study of this important carfilzomib-based combination
regimen." The Phase 1b portion of the multicenter dose-escalation
study enrolled 32 patients with relapsed and/or refractory multiple
myeloma and is designed to evaluate safety and maximum tolerated or
maximum per-protocol doses of carfilzomib with lenalidomide and
low-dose dexamethasone. Dr. Niesvizky presented initial data on 27
patients evaluable for safety and 29 patients evaluable for
efficacy. An additional 30 patients are being enrolled at the
maximum per-protocol doses of these agents in the Phase 2 portion
of this study; initial results are anticipated in that group in
2010. The phase 1b population received one to three prior regimens
for treatment of myeloma with 72 percent of the patients having
received prior bortezomib, 87 percent prior immunomodulatory drug
(IMiD) therapy (62 percent prior lenalidomide and 44 percent prior
thalidomide), and 97 percent prior steroids. Forty-seven percent of
the patients had disease refractory to the most recent therapy. The
carfilzomib, lenalidomide and low-dose dexamethasone combination
generated a response rate of 72 percent (minor response or better)
and 59 percent (partial response or better), even though it
included patients treated with less than maximal doses of
carfilzomib and lenalidomide. No dose-limiting toxicities were
observed and the maximum tolerated dose has not been reached. The
maximum per-protocol doses of 27mg/m2 carfilzomib and 25mg
lenalidomide were safely administered. This maximum dosage will be
administered in the Phase 2b portion of the trial and the planned
Phase 3 trial. Grade 3/4 adverse events were manageable and
expected including neutropenia (6 patients), anemia (4 patients),
hyperglycemia (3 patients), and thrombocytopenia (6 patients). The
regimen was well tolerated with prolonged administration of more
than 16 months, allowing for extended disease control. Initial
responses typically occurred within 1 to 2 cycles, with many
patients showing greater improvement over the subsequent months
while remaining on initial doses of each agent. "We believe
carfilzomib's unique profile may position it to be a promising
therapy to use in combination with one of the standard of care
treatment regimens for relapsed myeloma - the combination of
lenalidomide and low dose dexamethasone," said Michael Kauffman,
M.D., Ph.D., interim chief medical officer at Onyx. "We look
forward to initiating a Phase 3 trial in 2010 to evaluate
carfilzomib in combination with lenalidomide and low dose
dexamethasone, versus lenalidomide and dexamethasone alone, in
patients with relapsed multiple myeloma." Investor Teleconference
Principal investigators will discuss data presentations surrounding
carfilzomib in relapsed or refractory multiple myeloma, as featured
at ASH. The webcast event will begin at 9:00 a.m. CT/10:00 a.m. ET
on December 7, 2009. The live webcast will be available at:
http://www.onyx-pharm.com/view.cfm/32/Event-Calendar or by dialing
847-413-3362 and using the passcode 25914947. A replay of the
presentation will be available on the Onyx website or by dialing
630-652-3044 and using the passcode 25914947 later in the day. The
replay will be available on the Onyx website through January 7,
2010. About Carfilzomib Carfilzomib is a selective, next generation
proteasome inhibitor that has shown encouraging results in a broad
clinical trial program in multiple myeloma. Carfilzomib is
currently undergoing evaluation as a single agent in multiple Phase
2 and Phase 1 clinical trials in relapsed or refractory multiple
myeloma. These trials include a Phase 2b monotherapy study in
patients with relapsed, refractory multiple myeloma, the pivotal
trial that could support a new drug application (NDA) filing by the
end of 2010. Carfilzomib is also being evaluated in advanced solid
tumors. About Multiple Myeloma Multiple myeloma (MM) is the second
most common hematologic cancer and results from an abnormality of
plasma cells, usually in the bone marrow. In the United States,
more than 50,000 people are living with MM and approximately 20,000
new cases are diagnosed annually(i). Worldwide, more than 180,000
people are living with MM and approximately 86,000 new cases are
diagnosed annually(ii). 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, is currently in Phase 1 testing. For more information
about Onyx, visit the company's website at
http://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 anticipated benefits of the acquisition of
Proteolix and the timing, 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 the risk that Proteolix's operations will not be
integrated successfully into Onyx's, the risk that Onyx may not
realize the anticipated benefits of the acquisition and 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, 2008,
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) National Cancer Institute,
Surveillance Epidemiology and End Results, 2007 Facts and Figures
(ii) International Agency for Research on Cancer, GLOBOCAN 2002
database DATASOURCE: Onyx Pharmaceuticals, Inc. CONTACT: Investors,
Julie Wood, Vice President, Investor Relations, +1-510-597-6505,
Media, Lori Murray, Associate Director, Corporate Communications,
+1-510-597-6394, both of Onyx Pharmaceuticals, Inc. Web Site:
http://www.onyx-pharm.com/
Copyright