Clinical Phase I and II data presented at American Society of Clinical Oncology (ASCO) 2007 Annual Meeting
CHICAGO, IL, USA | June 5, 2007 | Medarex, Inc. (Nasdaq: MEDX) and Bristol-Myers Squibb Company (NYSE: BMY) today presented results from multiple clinical studies of ipilimumab (MDX-010), an investigational immunotherapy, for patients with advanced melanoma. The results demonstrated an anti-tumor response in some patients with advanced melanoma either as a monotherapy or in combination with other therapies. The results of the monotherapy study showed that 19% of patients (17/88) with advanced melanoma treated with ipilimumab experienced control of their disease, including tumor shrinkage and stabilization. The second presentation showed that complete or partial response was achieved in 13% of patients (46/356) with advanced melanoma when treated with ipilimumab alone or in combination with traditional chemotherapy (i.e., dacarbazine), interleukin-2, or a gp100 peptide vaccine. The results of this analysis also indicated that treatment with ipilimumab may take 12 weeks or longer to induce a response. These findings were presented at the American Society of Clinical Oncology’s 2007 Annual Meeting in Chicago.
"In recent years, there have been limited advancements in the treatment of melanoma, particularly in the later stages of the disease," said Rachel Humphrey, MD, Vice President of Development at Bristol-Myers Squibb. "These studies represent an important advance in our understanding of how ipilimumab may work as a potential anti-cancer therapy for patients with this devastating disease."
(Abstract #8523) Results from a Phase II dose-escalation trial presented by Jeffrey S. Weber, MD, PhD, who was Chief of Oncology at the Keck School of Medicine at the University of Southern California at the time of the study, suggested that the anti-tumor response evolves over time in certain patients treated with ipilimumab. The primary endpoint of the study was to investigate the safety and clinical activity of various doses of ipilimumab. The study enrolled 88 patients with unresectable stage III or stage IV malignant melanoma in three cohorts receiving varying doses and regimens. Analysis of the data demonstrated:
— Overall disease control – defined as objective responses (complete and partial) and stable disease – achieved in 19% (17/88) of patients.
– In the cohort of 23 patients who were treated at 10 mg/kg, disease control was achieved in 39% (9/23), which lasted six months o longer in nearly all patients (8/9).
–Duration of disease stabilization or response exceeded six months in 15% (13/88) of patients. The longest effect observed (stable disease) is ongoing for more than a year.
Adverse events reported in this study were consistent with those immune- related adverse events (irAEs) results in other clinical trials of ipilimumab (diarrhea, rash, adrenal insufficiency, elevated liver enzymes). In this study, the overall incidence of irAEs was 72% (63/88). All patients who achieved a response (complete or partial responses) and most patients who achieved stable disease (12/13) also reported an irAE – primarily grade 1 or 2 with the exception of grade 3 diarrhea (1/88), adrenal insufficiency (1/88) and liver abnormalities (1/88) in three patients with stable disease. Twenty- eight percent (25/88) of patients reported serious adverse events (SAEs) regardless of causality, nine of which were ipilimumab-related, but not dose dependent. Most events were reversible without sequelae.
(Abstract #8525) Analysis of data aggregated from six Phase I and II trials, presented by Omid Hamid, MD, an investigator at The Angeles Clinic and Research Institute in Los Angeles, California, showed durable objective responses and stable disease in some patients who received varying doses of ipilimumab (0.1 up to 20 mg/kg, single or multiple doses) alone or in combination with dacarbazine, interleukin-2, or gp100 peptide vaccine. The primary endpoint of this analysis was to examine the kinetics of response to ipilimumab in 356 patients with stage III or stage IV metastatic melanoma; secondary endpoints included duration of objective response (defined as complete or partial response) and stable disease. Analysis of the kinetics of response data demonstrated:
— Complete or partial response achieved in 13% (46/356) of patients. Of these 46 patients:
– 61% (28/46) achieved an objective response at week 12 or later
– 35% (16/46) achieved stable disease prior to objective response (complete or partial)
– 22% (10/46) achieved a partial response, which developed into a complete response
— Current median duration of stable disease (from five of the six studies) was more than 15.4 weeks (median duration of objective response has not yet been reached). Twenty-five patients continue to respond with the longest response still ongoing at five years.
As previously reported for each individual study, the most common adverse events were immune-related (irAEs) including rash and diarrhea, which were medically manageable and reversible with treatment.
"In some cases, responses were achieved at 12 weeks or later in patients whose disease progressed after treatment with ipilimumab, suggesting that continued treatment through apparent disease progression may be beneficial," said Geoffrey M. Nichol, MBChB, Senior Vice President of Product Development at Medarex. "Further research is needed to fully understand how immunotherapies differ from currently approved chemotherapies."
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 is believed to play 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.
Ipilimumab is being developed through a joint partnership between Bristol-Myers Squibb and Medarex. Ipilimumab is currently in Phase III development (under Special Protocol Assessments [SPA] with the U.S. Food and Drug Administration [FDA]) to study its effects on metastatic melanoma alone and in combination with chemotherapy. Ipilimumab also is in Phase I and II development for other types of cancers, including prostate, pancreatic, bladder, lymphoma and leukemia. In December 2006, ipilimumab received Fast Track designation from the FDA for use as a monotherapy in previously treated (second-line) metastatic melanoma patients, as well as in combination with chemotherapy (dacarbazine) in previously untreated (first-line) metastatic melanoma patients. Fast Track designation was also granted for ipilimumab as a second-line treatment in combination with a melanoma-peptide vaccine.
About 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 2007 there will be 59,940 new cases of melanoma in the U.S., and about 8,110 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(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 30 of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with six of the most advanced product candidates currently in Phase III 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 Web site at www.medarex.com.
Medarex Statement on Cautionary Factors: Except for the historical information presented herein, matters discussed herein may constitute forward- looking statements 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"; "believe"; "anticipate"; "intend"; "plan"; "expect"; "estimate"; "could"; "may"; or similar statements are forward-looking statements. Medarex disclaims, however, any intent or obligation to update these forward-looking statements. Risks and uncertainties include risks associated with ipilimumab development, uncertainties related to the outcome of clinical trials, slower than expected rates of patient recruitment, unforeseen safety issues resulting from the administration of antibody products in patients, uncertainties related to product manufacturing, risks associated with the use of hazardous substances 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, 2006 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 dedicated to the discovery, development and exhaustive exploration of innovative cancer fighting therapies designed to extend and enhance the lives of patients living with cancer. More than 40 years ago, Bristol-Myers Squibb built a unified vision for the future of cancer treatment. With expertise, dedication and resolve, that vision led to the development of a diverse global portfolio of anti-cancer therapies that are an important cornerstone of care today. Hundreds of scientists at Bristol-Myers Squibb’s Pharmaceutical Research Institute are studying ways to improve current cancer treatments and identify better, more effective medicines for the future.
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the development and commercialization of products. 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 the products described in this release will be successful, that the products described in this release will receive regulatory approval, or that if approved, 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, 2006, 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.
SOURCE: Medarex, Inc.; Bristol-Myers Squibb Company
