Medarex, Inc. (NASDAQ: MEDX) today announced anti-tumor activity and
efficacy data for MDX-1106 (also known as ONO-4538), a fully human
anti-PD-1 antibody that Medarex is co-developing with Ono Pharmaceutical
Co. Ltd. for the treatment of recurrent or treatment-refractory cancers,
including malignant melanoma, renal cell carcinoma, colorectal
carcinoma, non-small cell lung cancer, and castrate resistant prostate
carcinoma. Results presented at the annual meeting of the American
Society of Clinical Oncology (ASCO) showed:
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Durable anti-tumor activity in patients treated with intermittent 10
mg/kg dosing of MDX-1106 in the 21-patient expansion cohort from the
Phase 1 trial, including one patient with renal cell cancer
experiencing an ongoing objective partial response of over 9 months
and one patient with melanoma experiencing ongoing stable disease with
marked clinical improvement for over 19 months and 9 doses of
MDX-1106. One patient with colorectal carcinoma treated with five
doses at the earlier 3 mg/kg cohort has also maintained a partial
response for over 20 months;
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All patients showing clinical benefit with MDX-1106 had previously
progressed after prior chemotherapies;
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None of the patients treated at 10 mg/kg have developed any
significant drug-related adverse events. MDX-1106 appeared to be
well-tolerated at the 10 mg/kg dose, including those patients in the
cohort eligible to receive between two and nine doses of 10mg/kg
MDX-1106; and
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No dose-limiting toxicities have been reached.
These data focused on the experience of an expansion cohort of 21
patients dosed at 10 mg/kg of MDX-1106 from the single-dose Phase 1
trial and were presented by investigator Julie Brahmer, M.D., Assistant
Professor of Oncology from the Sidney Kimmel Comprehensive Cancer Center
at Johns Hopkins University (Abstract #3018). The complete study was
designed to examine the safety, tolerability and pharmacokinetic profile
of single-dose MDX-1106 (0.3, 1, 3 or 10 mg/kg) in patients with
recurrent or treatment-refractory cancers. However, per protocol,
patients demonstrating clinical benefit could receive additional
intermittent doses (up to nine doses of 10 mg/kg MDX-1106) until an
objective response was obtained. In addition to the durable responses
outlined above, lesional regressions were observed in two additional
patients, including one with non-small cell lung cancer, and one with
melanoma. Enrollment in the single-dose Phase 1 trial is complete with
39 patients.
Also presented were preliminary data from an ongoing multi-dose, dose
escalating Phase 1b monotherapy study of MDX-1106. One patient with
melanoma in the first treatment cohort of 4 patients has demonstrated
marked tumor regression of liver and lung lesions after receiving four
doses of 1 mg/kg of MDX-1106. The tumors have continued to shrink after
additional cycles of four doses, and the patient continues to tolerate
the treatment without adverse events. Additional anti-tumor activity has
been observed with lung lesion regression in a patient with renal cell
cancer. Subsequently observed in the second dose level cohort, one
patient with non-small cell lung cancer has demonstrated regression of a
solitary adrenal metastasis after the first 4 doses of 3 mg/kg of
MDX-1106. The trial is designed to examine the safety and activity in
patients treated with multiple doses of MDX-1106 (1, 3 and 10 mg/kg)
administered every two weeks until a confirmed complete response, clear
progression or serious adverse event emerges. This multi-center, open
label study is expected to enroll up to 76 patients in the United States.
"We are encouraged by both the safety profile and the initial anti-tumor
activity that included durable responses in several cancer indications
for patients treated intermittently with MDX-1106 up to the 10 mg/kg
dose. We are also pleased by our ongoing Phase 1b study of repeated
doses of the antibody which has also shown early evidence of activity at
a repeated dose of 1 or 3 mg/kg,” said Geoffrey M. Nichol, MBChB, Senior
Vice President of Product Development at Medarex. "While we are still in
early stages of development, it is also exciting that these treatments
continue to be generally well tolerated.”
About MDX-1106/ONO-4538
MDX-1106/ONO-4538 is a novel fully human antibody designed to target and
inhibit the function of PD-1 (programmed cell death 1), a receptor
expressed on the surface of activated lymphocytes (T-cells). The binding
of PD-1 with one of two ligands (PD-L1 or PD-L2) is an important
negative regulation pathway that suppresses or inhibits activated
lymphocytes. Recent research has noted increased PD-1 expression levels
on antigen specific T-cells in both the oncology and chronic infectious
disease settings, as well as a strong correlation between increased
PD-L1 expression on tumors and a negative survival prognosis in cancer
patients. Preclinical studies indicate that antibodies targeting the
PD-1 signaling pathway reinvigorate antigen-specific T-cell responses
and promote an immune response to fight tumors and infectious diseases.
MDX-1106/ONO-4538 is being investigated in both the oncology and
infectious disease settings. In addition to the Phase 1b study in
cancer, a Phase 1 trial is ongoing for the treatment of hepatitis C. In
September 2008, Ono initiated a single and multi-dose Phase 1 clinical
study in patients with advanced solid malignancies in Japan.
MDX-1106/ONO-4538 may also have the potential to be used synergistically
in combination with other treatment modalities, including with
anti-CTLA-4 blockade.
In May 2005, Ono entered into a collaboration agreement with Medarex to
research and develop a fully human anti-PD-1 antibody for the treatment
of cancer. The two companies plan to share the costs and
responsibilities of research and product development up to the
completion of a Phase 2 clinical study in each party’s territory.
Thereafter, each company will be fully responsible for any continued
development and any commercialization in its exclusive territory;
Medarex’s exclusive territory is North America, and Ono’s exclusive
territory is all areas outside of North America.
About Medarex
Medarex is a biopharmaceutical company focused on the discovery,
development and potential commercialization of fully human
antibody-based therapeutics to treat life-threatening and debilitating
diseases, including cancer, inflammation, autoimmune disorders and
infectious diseases. Medarex applies its UltiMAb® technology
and product development and clinical manufacturing experience to
generate, support and potentially commercialize a broad range of fully
human antibody product candidates for itself and its partners. Over
forty of these therapeutic product candidates derived from Medarex
technology are in human clinical testing or have had INDs submitted for
such trials, with the most advanced product candidates currently
approved for commercial sale, the subject of regulatory applications for
marketing authorization or in Phase 3 clinical trials. Medarex is
committed to building value by developing a diverse pipeline of antibody
products to address the world’s unmet healthcare needs. For more
information about Medarex, visit its website at www.medarex.com.
Medarex Statement on Cautionary Factors
Except for the historical information presented herein, the statements
relating to MDX-1106 in this press release may constitute
forward-looking statements, as defined in the Private Securities
Litigation Reform Act of 1995, that are subject to certain risks and
uncertainties that could cause actual results to differ materially from
any future results, performance or achievements expressed or implied by
such statements. Medarex disclaims, however, any intent or obligation to
update these forward-looking statements. Risks and uncertainties include
risks associated with product discovery and development of MDX-1106, as
well as risks detailed from time to time in Medarex’s public disclosure
filings with the U.S. Securities and Exchange Commission (SEC),
including its Annual Report on Form 10-K for the fiscal year ended
December 31, 2008 and its quarterly reports on Form 10-Q. There can be
no assurance that such development efforts will succeed or that
developed products will receive required regulatory clearance or that,
even if such regulatory clearance were received, such products would
ultimately achieve commercial success. Copies of Medarex’s public
disclosure filings are available from its investor relations department.
Medarex®, the Medarex logo and UltiMAb® are registered trademarks of
Medarex, Inc. All rights are reserved.
