The New England Journal of Medicine Publishes Millennium's Phase III Results of VELCADE(R) (Bortezomib) for Injection in Previously Untreated Multiple Myeloma Patients; Velcade Found Better Than Standard Drug

CAMBRIDGE, Mass., Aug. 27 /PRNewswire/ -- Millennium: The Takeda Oncology Company today announced the publication of results from the 682 patient, randomized, Phase III VISTA(1) trial in this week's edition of the New England Journal of Medicine. The results showed a significant survival benefit and a 30 percent complete remission (CR) rate with VELCADE, melphalan and prednisone (VcMP) compared to 4 percent for melaphalan and prednisone (MP) alone in previously untreated multiple myeloma patients. Multiple myeloma is the second most common blood cancer.

(Logo: http://www.newscom.com/cgi-bin/prnh/20080827/NEW076LOGO )

"These data demonstrate that treatment with VELCADE plus melphalan and prednisone leads to a survival benefit and a high complete remission in previously untreated patients with multiple myeloma," said Professor Jesus San Miguel, M.D., Ph.D., Hematology Department Head, University Hospital of Salamanca and Principal Investigator of the trial. "The combination of VELCADE plus melphalan and prednisone is an important new option for these patients."

These data originally were presented at the 2007 American Society of Hematology (ASH) Annual Meeting. Based on these positive trial results, the U.S. Food and Drug Administration approved VELCADE for patients with previously untreated multiple myeloma on June 20, 2008. The Phase III VISTA trial was conducted by Millennium and its co-development partner Johnson & Johnson Pharmaceutical Research & Development, L.L.C. in 151 centers worldwide.

"We are proud to have these data published in such a highly esteemed journal," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "We're delighted that previously untreated multiple myeloma patients now can benefit from this VELCADE based therapy as have patients in the relapsed and refractory settings since 2003."

(1) VELCADE as Initial Standard Therapy in multiple myeloma: Assessment with melphalan and prednisone

VISTA Trial Results

Patient responses were evaluated by the stringent European Group for Blood and Marrow Transplantation (EBMT) criteria:

-- A CR rate of 30 percent in the VcMP arm compared to 4 percent with MP (p<0.001)

-- VcMP demonstrated statistical significance in overall survival with a 39 percent reduction in risk of death (Hazard ratio= 0.61; p=0.008) with a follow-up of 16.3 months

-- The median treatment duration was 46 weeks for the VcMP arm compared to 39 weeks for the control arm and discontinuation due to adverse events was similar in both arms

Patients in the VcMP arm received VELCADE at 1.3 mg/m2 twice weekly in weeks one, two, four and five for four six-week cycles (eight doses per cycle), followed by once weekly on weeks one, two, four and five for up to five six-week cycles (four doses per cycle) in combination with melphalan at 9 mg/m2 and prednisone at 60 mg/m2 once daily on days 1 through 4 of each cycle for up to nine six-week cycles. For both groups, treatment continued for a maximum of 54 weeks.

"The tolerability of VcMP also was encouraging and side effects were generally manageable with appropriate supportive care and dose reduction as needed," commented Paul Richardson, M.D., Clinical Director of the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and Senior Investigator on the study.

The safety profile of VELCADE in combination with MP is consistent with the known safety profiles of both VELCADE and MP. In VISTA, the most commonly reported adverse events for VELCADE in combination with MP vs MP, respectively, were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%), nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%), anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs 1%), leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%), fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%), asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs 10%), rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%), dizziness (16% vs 11%), dyspnea (15% vs 13%), headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal pain (14% vs 7%), paresthesia (13% vs 4%), herpes zoster (13% vs 4%), bronchitis (13% vs 8%), hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension (12% vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs 10%), arthralgia (11% vs 15%) and pruritus (10% vs 5%).

Important Safety Information

In the U.S., VELCADE is indicated for the treatment of patients with multiple myeloma. VELCADE also 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 throughout therapy, cardiac and pulmonary disorders, reversible posterior leukoencephalopathy syndrome, gastrointestinal adverse events, thrombocytopenia, neutropenia, tumor lysis syndrome and hepatic events. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Nursing mothers are advised not to breastfeed while receiving 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 new onset of decreased left ventricular ejection fraction has been reported, including reports in patients with no risk factors for decreased left ventricular ejection fraction. There have been reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome in patients receiving VELCADE. Some of these events have been fatal. There have been reports of Reversible Posterior Leukoencephalopathy Syndrome (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. Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Patients who are concomitantly receiving VELCADE and drugs that are inhibitors or inducers of cytochrome P450 3A4 should be closely monitored for either toxicities or reduced efficacy. Patients on oral antidiabetic medication while receiving VELCADE should check blood sugar levels frequently.

Adverse Reaction Data

Safety data from Phase II and III studies of single-agent VELCADE 1.3 mg/m2/dose twice weekly for 2 weeks followed by a 10-day rest period in 1163 patients with previously treated multiple myeloma (N=1008, not including the Phase III, VELCADE plus DOXIL(R) [doxorubicin HCl liposome injection] study) and previously treated mantle cell lymphoma (N=155) were integrated and tabulated. In these studies, the safety profile of VELCADE was similar in patients with multiple myeloma and mantle cell lymphoma.

In the integrated analysis, the most commonly reported adverse events were asthenic conditions (including fatigue, malaise and weakness) (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy NEC (including peripheral sensory neuropathy and peripheral neuropathy aggravated) (39%), thrombocytopenia and appetite decreased (including anorexia) (each 36%), pyrexia (34%), vomiting (33%), anemia (29%), edema (23%), headache, paresthesia and dysesthesia and headache (each 22%), dyspnea (21%), cough and insomnia (each 20%), rash (18%), arthralgia (17%), neutropenia and dizziness (excluding vertigo) (each 17%), pain in limb and abdominal pain (each 15%), bone pain (14%), back pain and hypotension (each 13%), herpes zoster, nasopharyngitis, upper respiratory tract infection, myalgia and pneumonia (each 12%), muscle cramps (11%), and dehydration and anxiety (each 10%). Twenty percent (20%) of patients experienced at least 1 episode of greater than or equal to Grade 4 toxicity, most commonly thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients experienced serious adverse events (SAEs) during the studies. The most commonly reported SAEs included pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%).

About Multiple Myeloma

Multiple myeloma is the second most common hematological malignancy. Between 2001 - 2005, the median age of diagnosis was 70 years. In 2007, there were 110,000 patients living with multiple myeloma across the United States, Europe and Japan. It is estimated that this number will increase by 5.6 % annually over the next few years due to new therapies extending the lives of multiple myeloma patients.

About VELCADE

VELCADE is being co-developed by Millennium: The Takeda Oncology Company and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium is responsible for commercialization of VELCADE in the U.S. and 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 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 Millennium

Millennium: The Takeda Oncology Company, and a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a novel cancer product, and has a robust clinical development pipeline of product candidates. Millennium research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, www.millennium.com.

CONTACT: Karen Gobler, +1-617-444-1392, karen.gobler@mpi.com

Web site: http://www.millennium.com/

Company News On-Call: http://www.prnewswire.com/comp/114562.html /