New England Journal of Medicine Publishes Studies of VELCADE(R) (bortezomib) for Injection in Multiple Myeloma and MLN02 in Ulcerative Colitis
Thursday June 16, 8:01 am ET
-- VELCADE demonstrated survival advantage in relapsed multiple myeloma patients; MLN02 showed statistical significance in achieving remissions in ulcerative colitis --
CAMBRIDGE, Mass., June 16 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM - News) today announced the publication of results from two clinical trials in this week's New England Journal of Medicine. The first publication reports results from the phase III APEX study which showed VELCADE was superior in survival, time to disease progression, and response rates compared to standard of care, high-dose dexamethasone, in patients with relapsed multiple myeloma (MM). Results from a second study, published in the same issue, detail findings from a randomized phase II trial of the investigational drug MLN02 in patients with ulcerative colitis that demonstrated statistically significant improvements in remission rates in patients compared to placebo, the trial's primary endpoint.
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"We are delighted to have two studies published simultaneously in the prestigious New England Journal of Medicine," said Bob Tepper, president, research and development, Millennium. "We believe it is a testament to the potential of VELCADE to change the treatment paradigm in multiple myeloma. The MLN02 study results demonstrate the importance of this first-in-class drug as a potential novel treatment for ulcerative colitis patients and exemplify the quality of our R&D pipeline."
The APEX study was halted at interim analysis in December 2003 at the recommendation of an independent Data Monitoring Committee due to significant prolongation of time to disease progression and significantly improved overall survival. Based on these study findings, the U.S. Food and Drug Administration approved a supplemental New Drug Application in March 2005 for VELCADE use in MM patients who have received at least one prior therapy. To date, more than 24,000 patients have been treated with VELCADE in more than 50 countries. Millennium and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) are currently investigating the potential benefit of VELCADE for the treatment of MM patients in the front-line setting in multiple phase III registration trials for MM. Millennium and J&JPRD are assessing VELCADE globally in other hematologic and solid tumors including non-Hodgkin's lymphoma and lung, prostate and ovarian cancers.
VELCADE® (bortezomib) For Injection APEX Trial Confirms Survival Benefit
The APEX trial was conducted at 93 centers in North American, Europe and Israel and enrolled 669 MM patients who had received one to three prior therapies and randomized them to either treatment with single agent VELCADE or high-dose dexamethasone. Results from 627 evaluable patients (315 treated with VELCADE and 312 treated with dexamethasone) after a median 8.3 months follow- up included:
* Statistically significant survival advantage for patients treated in
the single agent VELCADE arm which was maintained even though 44
percent of patients crossed over to receive VELCADE after experiencing
progressive disease on the dexamethasone arm;
* One-year survival rate with VELCADE was 80 percent compared to 66
percent with dexamethasone;
* Complete plus partial response rate with VELCADE was 38 percent
compared to 18 percent with dexamethasone;
* Statistically significant higher complete and near complete responses
(13 versus two percent) were also found with VELCADE; and
* Median time to progression was improved by 78 percent (6.2 months on
VELCADE versus 3.5 months for dexamethasone).
"The study results highlight the advantage of VELCADE in extending the survival of relapsed multiple myeloma patients," said Dr. Paul Richardson, M.D., Dana Farber Cancer Institute and author of the paper. "Also exciting are the recent results of investigations of VELCADE based regimens in the front- line setting that have suggested the potential of VELCADE to improve the quality of responses when received earlier in treatment."
A prospective analysis was conducted in patients who had received only one prior therapy (38 percent of the overall patients in the study) which also demonstrated significantly improved outcomes. Importantly, results showed that outcomes improved when VELCADE was given to patients in earlier lines of therapy. Results included:
* Patients treated with VELCADE versus dexamethasone demonstrated
statistically improved survival;
* Forty-five percent of patients achieved a complete or partial response
with VELCADE compared to 26 percent for dexamethasone; and
* Median time to progression was also significantly improved (7.0 months
on VELCADE versus 5.6 months for dexamethasone).
Adverse events reported in patients treated with VELCADE were as previously reported and included gastrointestinal events, fatigue, neuropathy, pyrexia and hematologic toxicities. Patients treated with dexamethasone reported predictable adverse events including fatigue, insomnia, anemia and diarrhea. The duration of treatment each patient received, rate of serious adverse events and rate of discontinuation due to an adverse event were similar in both treatment groups.
MLN02 Phase II Study Results Show Statistical Improvement Across All Endpoints
Also published in this week's New England Journal of Medicine were results from a double-blind, multicenter phase II trial of the Company's investigational drug MLN02 in patients with ulcerative colitis. A total of 181 patients with moderately active ulcerative colitis were randomized to receive either a 0.5 mg/kg dose of MLN02, a 2.0 mg/kg dose of MLN02 or placebo at days one and 29. The primary outcome was clinical remission at week six, as defined as a score of zero or one on the Ulcerative Colitis Clinical Score (UCCS) and a score of zero or one on the Modified Baron Score (MBS) with no evidence of rectal bleeding at the study's conclusion. Key findings included:
* Clinical remission was achieved in 33 percent of the patients receiving
0.5 mg/kg of MLN02 and 32 percent of the patients receiving 2.0 mg/kg
of MLN02 versus 14 percent in those who had received placebo. These
remission rates are statistically significant;
* Endoscopic remission was achieved in 28 percent of patients receiving
0.5 mg/kg of MLN02 and 12 percent of patients receiving 2.0 mg/kg of
MLN02, compared to eight percent of those who received placebo. An
endoscopic remission is defined as a MBS of zero;
* Statistically significant clinical response was achieved in 66 percent
of patients (0.5 mg/kg) and 53 percent (2.0 mg/kg) in the treatment
groups, compared to 33 percent of those who received placebo. Clinical
response is defined as an improvement of three or more points on the
UCCS from baseline; and
* The drug was generally well tolerated. Serious adverse events were
comparable in the three treatment groups and were mainly related to
exacerbations of underlying ulcerative colitis, which occurred in 15
percent of patients in the two treatment groups, compared to 10 percent
in the placebo group. An infusion reaction occurred in one MLN02
treated patient who developed hives and mild angioedema.
"These data provide additional clinical validation to the benefits of inhibiting cell trafficking in treating chronic inflammatory diseases," said Nancy Simonian, M.D., senior vice president, clinical development, regulatory and medical affairs, Millennium. "MLN02 is particularly exciting because it selectively inhibits cell trafficking to the GI tract and not to other organs which may reduce the risk of infections. We are currently working on a commercially scalable cell line and hope to initiate new studies in 2006."
About VELCADE® (bortezomib) for Injection
VELCADE is indicated for the treatment of multiple myeloma patients 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, cardiac disorders, gastrointestinal adverse events, thrombocytopenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE.
In 331 patients who were treated with VELCADE in a phase III study, the most commonly reported adverse events were asthenic conditions (61%), diarrhea (57%), nausea (57%), constipation (42%), peripheral neuropathy (36%), vomiting (35%), pyrexia (35%), thrombocytopenia (35%), psychiatric disorders (35%), anorexia and appetite decreased (34%), parasthesia (27%), dysesthesia (27%), anemia and headache (26%), and cough (21%). Fourteen percent of patients reported at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (4%), neutropenia (2%), and hypercalcemia (2%). A total of 144 patients on VELCADE (44%) reported serious adverse events (SAEs) during the study. The most commonly reported SAEs were pyrexia (6%), diarrhea (5%), dyspnea, pneumonia (4%), and vomiting (3%).
VELCADE® (bortezomib) for Injection is being co-developed by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD). Millennium is responsible for commercialization of VELCADE in the U.S.; Ortho Biotech and Janssen-Cilag are responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for commercialization in Japan. VELCADE is approved in more than 50 countries worldwide, including the U.S., European Union and a number of countries within Latin America and South-East Asia. VELCADE is also approved in the European Union as a second-line treatment. It is indicated as a monotherapy for use in patients with progressive MM who have received at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplantation. Millennium and J&JPRD continue to investigate VELCADE globally in phase I, II and III clinical trials in both hematologic and solid tumors, including front-line MM, non-Hodgkin's lymphoma and lung, prostate and ovarian cancers.
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).
About MLN02
MLN02 is an investigational, novel monoclonal antibody that binds to alpha 4 beta 7, a T-cell integrin (a cell surface protein). In laboratory studies, the mechanism of action has shown to prevent the migration of T-cells specifically to the GI tract. Increased T-cell trafficking is believed to play a role in the pathogenesis of inflammatory bowel disease (IBD), including conditions such as ulcerative colitis and Crohn's disease.
About Millennium
Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a novel cancer product, co- promotes INTEGRILIN® (eptifibatide) Injection, a market-leading cardiovascular product, and has a robust clinical development pipeline of product candidates. The Company's research, development and commercialization activities are focused in three therapeutic areas: oncology, cardiovascular, and inflammation. By applying its knowledge of the human genome, its understanding of disease mechanisms, and its industrialized drug discovery platform, Millennium is seeking to develop breakthrough products. |
