Bristol-Myers
Squibb Company (NYSE: BMY) and Medarex,
Inc. (NASDAQ: MEDX) today announced updated survival data from three
Phase 2 studies of ipilimumab in patients with advanced metastatic
melanoma (Stage III or IV) who had previously been treated. Study
results show that approximately half of patients who received ipilimumab
(10 mg/kg) remained alive beyond one year.
The results are based on follow-up of the patient population from
studies 008, 022 and 007 treated with 10 mg/kg of ipilimumab (induction
and maintenance) and show a consistent one-year survival rate between 47
and 51 percent. Specifically, the results show:
-
One-year survival rate of 47 percent in patients who had progressed
while on or after receiving standard treatment (Study 008, Abstract
#776PD);
-
One-year survival rate of 48 percent in patients who were previously
treated, relapsed or failed to respond to experimental treatment or
were unable to tolerate currently approved therapies (Study 022,
Abstract #769O);
-
One-year survival rate of 51 percent in patients previously treated
with therapy other than ipilimumab (Study 007, Abstract #778PD).
Follow-up for survival was up to 24.8, 21.88 and 26.32 months in studies
008, 022 and 007, respectively.
Recent medical literature based on a meta-analysis of 42 Phase 2 trials
with 2,100 patients reported a one-year survival rate of approximately
25 percent for patients with Stage III or IV metastatic melanoma, the
most advanced type of the disease1.
"Currently, there are few treatment options
available for patients with advanced melanoma,”
said Michele Maio, M.D., Ph.D. Director, Division of Medical Oncology
and Immunotherapy, University Hospital of Siena. "As
these data on ipilimumab continue to mature, we are encouraged by the
durability of response and consistency of survival results observed
across all three Phase 2 studies.”
Safety results from the three studies were generally consistent with
data from previously reported clinical trials of ipilimumab. The most
common immune-related adverse events were rash, diarrhea and hepatitis.
Grade 3 and 4 immune-related adverse event rates were approximately 20
to 28 percent and zero to 12 percent, respectively, in patients who
received 10 mg/kg of ipilimumab. Adverse events were generally
manageable and reversible within days or weeks with the use of
supportive care and systemic steroids using established treatment
guidelines in the majority of patients.
Additional data on efficacy and survival with an active control group
will come from an ongoing Phase 3, randomized, double-blind study (024)
assessing ipilimumab (10 mg/kg) in combination with dacarbazine (DTIC)
versus DTIC alone in patients with untreated, unresectable Stage III or
Stage IV metastatic melanoma. A Phase 3 study (029) of ipilimumab
administered as adjuvant therapy in patients with high-risk Stage III
metastatic melanoma is also currently being conducted.
"We are excited by the consistent one-year
survival rates among the three Phase 2 studies,”
said Geoffrey M. Nichol, MBChB, Senior Vice President of Product
Development at Medarex. "Medarex and
Bristol-Myers Squibb remain fully committed to the registrational
program, including advanced melanoma, adjuvant melanoma, lung and
prostate cancer trials.”
About Studies 008, 022 and 007
The three studies enrolled a total of 487
patients across North
America, Europe, South America, Africa and Australia with Stage III or
Stage IV metastatic melanoma treated with 0.3 mg/kg, 3.0 mg/kg or 10
mg/kg of ipilimumab therapy. Approximately half of the patients in each
of the trials had stage M1c disease, which indicates that cancer has
spread to internal organs. M1c disease can also be associated with an
elevated level of serum cholesterol and lactate dehydrogenase (LDH) and
is typically indicative of the worst prognosis. Additionally, 10 percent
of patients in study 007 had brain metastases at baseline as determined
by an Independent Review Committee (IRC). Specifically, the three Phase
2 monotherapy trials include:
-
A Phase 2 open-label, single-arm trial (008) evaluating overall
response rate in 155 patients who progressed while on or after
receiving standard treatment;
-
A Phase 2 randomized, double-blind trial (022) evaluating the efficacy
of three dose levels of ipilimumab in 217 patients who were previously
treated, relapsed or failed to respond to experimental treatment or
were unable to tolerate currently approved therapies; and
-
A Phase 2 randomized, double-blind trial (007) evaluating the rate of
Grade 2+ diarrhea in 115 patients receiving ipilimumab with or without
prophylactic oral budesonide.
The primary endpoint of studies 008 and 022 was best overall response
rate and the primary endpoint of study 007 was to compare the rate of
Grade 2+ diarrhea in patients receiving ipilimumab with or without
prophylactic oral budesonide. Overall survival, one-year survival rates,
disease control rate, stable disease, and other measurements of
anti-tumor activity and patterns of responses were secondary endpoints
in studies 008, 022 and 007.
About Ipilimumab
Ipilimumab is a fully human antibody that binds to CTLA-4 (cytotoxic T
lymphocyte-associated antigen 4), a molecule on T-cells that plays a
critical role in regulating natural immune responses. The absence or
presence of CTLA-4 can augment or suppress the immune system’s
T-cell response in fighting disease. Ipilimumab is designed to block the
activity of CTLA-4, thereby sustaining an active immune response in its
attack on cancer cells.
About Advanced Melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled
growth of pigment-producing cells (melanocytes) located in the skin. As
with many cancers, it is more difficult to treat once the disease has
spread beyond the skin to other parts of the body by way of the
bloodstream or the lymphatic system (metastatic disease). Melanoma
accounts for about three percent of skin cancer cases, but it causes
most skin cancer deaths. The American Cancer Society estimates that in
2008, there will be 62,480 new cases of melanoma in the U.S., and about
8,420 people will die of this disease.
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.
More than 40 of these therapeutic product candidates derived from
Medarex technology are in human clinical testing or have had INDs
submitted for such trials, with seven of the most advanced product
candidates currently in Phase 3 clinical trials or the subject of
regulatory applications for marketing authorization. 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 Web site at www.medarex.com.
Except for the historical information presented herein, matters
discussed herein 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. Statements that
are not historical facts, including statements preceded by, followed by,
or that include the words; "potential"; "may"; or similar statements are
forward-looking statements. Medarex disclaims, however, any intent or
obligation to update these forward-looking statements. These risks and
uncertainties include whether the actual results in the clinical studies
described above will differ materially from results in future use of
ipilimumab, whether development of ipilimumab will be successful,
whether the clinical studies described in this release will support the
filing of a BLA with the FDA, or whether, if a BLA is filed with the
FDA, it will be filed in the time frame developed by the parties or will
receive regulatory approval, 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, 2007 and its quarterly reports on
Form 10-Q. There can be no assurance that such development efforts will
succeed or that other 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.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to extend and enhance human life. For more information, visit www.bms.com.
This press release contains "forward-looking statements" as that term is
defined in the Private Securities Litigation Reform Act of 1995,
regarding the research and development of ipilimumab. Such
forward-looking statements are based on current expectations and involve
inherent risks and uncertainties, including factors that could delay,
divert or change any of them, and could cause actual outcomes and
results to differ materially from current expectations. No
forward-looking statement can be guaranteed. Among other risks, there
can be no guarantee that the development of ipilimumab will be
successful or that the clinical studies described in this release will
support the filing of a Biological License Application (BLA) with the
U.S. Food and Drug Administration (FDA). Furthermore, there can be no
assurances that if a BLA is filed with the FDA, that it will be filed in
the timeframe developed by the parties or that such BLA will receive
regulatory approval. There can be no assurances that if approved,
ipilimumab will be commercially successful. Forward-looking statements
in the press release should be evaluated together with the many
uncertainties that affect Bristol-Myers Squibb's business, particularly
those identified in the cautionary factors discussion in Bristol-Myers
Squibb's Annual Report on Form 10-K for the year ended December 31,
2007, its Quarterly Reports on Form 10-Q, and Current Reports on Form
8-K. Bristol-Myers Squibb undertakes no obligation to publicly update
any forward-looking statement, whether as a result of new information,
future events, or otherwise.
1 Korn, E. "Meta-analysis
of Phase 2 Cooperative Group Trials in Metastatic Stage IV Melanoma to
Determine Progression-Free and Overall Survival Benchmarks for Future
Phase 2 Trials.”
Journal of Clinical
Oncology.2008; 26 (4):526-534. Bedikian AY, et al.
"Bcl-2
antisense (oblimersen sodium) Plus Dacarbazine in Patients with Advanced
Melanoma: The Oblimersen Melanoma Study Group.”
Journal of Clinical Oncology. 2006; 24(29):4738-45.