September 15, 2008
Updated Survival Data From Three Phase 2 Ipilimumab Studies Showed Almost Half of Previously Treated Metastatic Melanoma Patients Alive Beyond One Year
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 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 disease(1).
"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.
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.
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(R) 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.