Healthcare Industry News: Ortho Biotech
News Release - December 11, 2006
VELCADE(R) (Bortezomib) for Injection Demonstrates Substantial Activity Across Range of LymphomasPhase II trials report high overall response rates in relapsed patients
ORLANDO, Fla., Dec. 11 (HSMN NewsFeed) -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM ) today reported overall response rates (ORR) as high as 75 percent from Phase II clinical trials of VELCADE® (bortezomib) for Injection combination therapy across four subtypes of non-Hodgkin's lymphoma (NHL): follicular, marginal zone, mantle cell lymphoma (MCL) and T-cell lymphoma. These data include positive results from the Phase II study of VELCADE in combination with rituximab in follicular lymphoma, which served as the basis for an ongoing Phase III registration-enabling trial initiated earlier this year. The findings were presented at the 48th Annual Meeting of the American Society of Hematology (ASH) being held December 9-12, 2006, in Orlando, Fla.
"These results build on the strong single-agent activity previously seen with VELCADE in NHL and represent a significant step forward in accelerating and expanding the development of VELCADE in combination for the treatment of a variety of lymphomas," said Andy Boral, M.D., Ph.D., Senior Medical Director, Millennium. "Our recent approval in MCL demonstrates the ability of VELCADE to provide significant benefit to patients, even with the most aggressive types of lymphoma, and may lead to the establishment of a new standard of care."
VELCADE received full approval from the U.S. Food and Drug Administration (FDA) on December 8, 2006 for treatment of patients with MCL who have received at least one prior therapy, marking the first indication for VELCADE in lymphoma and the first therapy to receive FDA approval in this treatment setting.
Phase II Study of VELCADE (Bortezomib) Weekly or Twice Weekly Plus Rituximab in Patients with Follicular or Marginal Zone Lymphoma: Final Results (Abstract #694)
The multicenter Phase II study evaluated the safety and efficacy of VELCADE in combination with rituximab in 81 patients with follicular or marginal zone lymphoma. Response was evaluated by independent radiology review and by investigator assessment using the International Workshop Response Criteria (IWRC). Patients were randomized to receive either four weekly VELCADE doses at 1.6 mg/m2 on a 35-day cycle or twice-weekly VELCADE at 1.3 mg/m2 on a 21-day cycle. All patients received weekly rituximab at its regular weekly dose of 375 mg/m2 for four weeks. Patients were treated for a maximum of three cycles in the weekly VELCADE arm and five cycles in the twice-weekly VELCADE arm. The data were presented by Sven de Vos, M.D., Ph.D., of UCLA Medical Center in Los Angeles, Calif. Final results showed:
* By investigator assessment using the IWRC: -- ORR (complete response [CR], complete response unconfirmed [CRu] and partial response [PR]) was 53 percent among patients treated with once-weekly VELCADE and 57 percent among patients treated in the twice-weekly arm
-- Median time to progression (TTP) was nine months among patients treated with once- weekly VELCADE and 9.9 months among patients treated with twice-weekly VELCADE
* By independent radiology review: -- ORR was 38 percent among patients treated with weekly VELCADE and 46 percent treated with twice-weekly VELCADE
-- Median TTP was 9.7 months among patients treated with VELCADE weekly and 5.2 months among patients treated with VELCADE twice-weekly
* The total amount of VELCADE received was similar in both arms * Therapy was well tolerated; the most common adverse events with both weekly and twice-weekly VELCADE were fatigue, gastrointestinal events and peripheral neuropathy
* The weekly dosing schedule was determined to have similar efficacy to the twice-weekly schedule with the additional benefits of fewer grade 3 and 4 toxicities and a more convenient dosing schedule
* Based on these results, a randomized Phase III trial of VELCADE in combination with rituximab compared to rituximab alone was initiated earlier this year under a Special Protocol Assessment with the FDA
Marked Activity of VELCADE (Bortezomib), Rituximab and Dexamethasone in Relapsed and Refractory Mantle Cell Lymphoma (Abstract #2753)
The single-arm Phase II study evaluated the efficacy and safety of VELCADE in combination with rituximab and dexamethasone in 12 evaluable patients with relapsed MCL. VELCADE at 1.3 mg/m2 was administered on days 1, 4, 8 and 11, rituximab at 375 mg/m2 was administered on day 1, and oral dexamethasone at 40 mg was administered on days one through four. Cycles were repeated every three-weeks for six cycles. The study was presented by Johannes Drach, M.D., of the Medical University of Vienna, Austria. Results showed:
* ORR was 75 percent with 25 percent of patients achieving a CR * All patients who achieved CR were progression free at 12 months * Therapy was well tolerated; the most common adverse events included infections, peripheral neuropathy and fatigue
Phase II Study of Proteasome Inhibitor VELCADE (Bortezomib) in Patients with Relapsed/Refractory T-cell Lymphoma: Preliminary Results (Abstract #2462)
The Phase II study evaluated the efficacy and safety of single-agent VELCADE in 12 evaluable previously treated patients with peripheral T-cell lymphoma. Response was assessed using the National Cancer Institute Working Group criteria. VELCADE was administered at 1.3 mg/m2 on days 1, 4, 8 and 11 during a 21-day cycle for up to six cycles. The study was led by Pier Luigi Zinzani, M.D., Unit of Cardiology and Hematology, Institute of Hematology and Medical Oncology, University of Bologna, Bologna, Italy. Interim results showed:
* ORR was 67 percent including 17 percent of patients achieving a CR * Treatment was well tolerated; the most frequent adverse events were neutropenia, thrombocytopenia and peripheral neuropathy
About Non-Hodgkin's Lymphoma Non-Hodgkin's lymphoma (NHL) is the most common hematological cancer, the fifth leading cause of cancer death and the second fastest growing form of cancer in the U.S.(1) The prevalence of NHL is approximately 400,000 patients, 77,000 patients with follicular lymphoma and 10,000 with mantle cell lymphoma. There are approximately 54,000 new cases of NHL diagnosed per year, and 19,000 deaths are attributed to the disease annually(2,3).
Mantle cell lymphoma is an aggressive, rapidly progressive subtype of NHL, and is not curable with standard treatment. Because there is no generally accepted treatment approach and options often are limited, there is a growing need for new therapies. The average life expectancy for a patient with relapsed mantle cell lymphoma is one year.
VELCADE is being co-developed by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium is responsible for commercialization of VELCADE in the U.S.; Janssen-Cilag is responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for commercialization in Japan. For a limited period of time, Millennium and Ortho Biotech Inc. will co-promote VELCADE in the U.S. VELCADE also is approved in the European Union after first relapse.
VELCADE is indicated for the treatment of patients with multiple myeloma who have received at least one prior therapy. VELCADE is indicated for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron or mannitol. VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy.
Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension observed throughout therapy, cardiac and pulmonary disorders, gastrointestinal adverse events, thrombocytopenia, neutropenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Cases of severe sensory and motor peripheral neuropathy have been reported. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma. Acute development or exacerbation of congestive heart failure, and/or new onset of decreased left ventricular ejection fraction has been reported, including reports in patients with few or no risk factors for decreased left ventricular ejection fraction. There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome (ARDS) in patients receiving VELCADE. Some of these events have been fatal. A higher proportion of these events have been reported in Japan. There have been rare reports of RPLS in patients receiving VELCADE. RPLS is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. VELCADE is associated with thrombocytopenia and neutropenia. There have been reports of gastrointestinal and intracerebral hemorrhage in association with VELCADE. Transfusions may be considered. Complete blood counts (CBC) should be frequently monitored during treatment with VELCADE. Rare cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions.
Safety Data: In 1163 patients in MM and MCL studies, the most commonly reported adverse events were asthenic conditions (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy (39%), thrombocytopenia (36%), appetite decreased, including reports of anorexia (36%), pyrexia (34%), vomiting (33%) and anemia (29%). Twenty percent of patients reported at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (5%) and neutropenia (3%). Fifty percent of patients reported serious adverse events (SAEs). The most commonly reported SAEs were pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%).
For more information about VELCADE clinical trials, patients and physicians can contact the Millennium Medical Product Information Department at 1-866-VELCADE (1-866-835-2233).
Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a novel cancer product, and has a robust clinical development pipeline of product candidates. The Company's research, development and commercialization activities are focused in two therapeutic areas: oncology and inflammation. By applying its knowledge of the human genome, understanding of disease mechanisms and industrialized drug discovery platform, Millennium is developing an exciting pipeline of innovative product candidates. The Company's website is www.millennium.com.
This press release contains "forward-looking statements," including statements about the Company's growth and development of products. Various important risks may cause the Company's actual results to differ materially from the results indicated by these forward-looking statements, including: adverse results in its drug discovery and clinical development programs; failure to obtain patent protection for its discoveries; commercial limitations imposed by patents owned or controlled by third parties; the Company's dependence upon strategic alliance partners to develop and commercialize products and services based on its work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from its development efforts; product withdrawals; competitive factors; difficulties or delays in manufacturing the Company's products; government and third party reimbursement rates; the commercial success of VELCADE and INTEGRILIN® (eptifibatide) Injection; achieving revenue consistent with internal forecasts; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. For a further list and description of the risks and uncertainties the Company faces, see the reports it has filed with the Securities and Exchange Commission. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Editors' Note: This press release is also available under the Media section of the Company's website at: www.millennium.com.
1. 2005, American Cancer Society, Inc., Surveillance Research.
2. SEER, SARGA, and Decision Resources (for growth rate) data.
3. Federico et al., BLOOD 95(3): 783-789; 2000.
Source: Millennium Pharmaceuticals
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