VELCADE (Bortezomib) for Injection Based Therapy Delivers Sustained Overall Survival Advantage in Patients with Previously Untreated Multiple Myeloma
-- Data show 35 percent reduction in risk of death –
NEW ORLEANS--(BUSINESS WIRE)--Dec 8, 2009 - Millennium: The Takeda Oncology Company today reported updated results based on a planned median three-year follow up of patients from the large, international Phase III VISTA1 trial. These data were presented at the 51st Annual Meeting of the American Society of Hematology (ASH), held December 5-8, 2009 in New Orleans, Louisiana. These data were the basis for a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) earlier this year. The FDA has granted priority review status to that application.
The data showed that patients treated with VELCADE, melphalan and prednisone (VMP) had significantly longer overall survival (OS) at three years than those treated with melphalan and prednisone (MP), a commonly used standard of care (p=0.0008). This translated into a 35 percent reduction in risk of death (hazard ratio 0.65). VELCADE based therapy achieved improved OS in both young and advanced age patients, patients with normal and abnormal renal function and patients with standard and high-risk cytogenetics. The survival benefit of VMP persisted despite the use of salvage therapy with novel agents at relapse. Median survival has not yet been reached in the VMP arm.
"Prolonging the patient's overall survival is the ultimate goal in multiple myeloma treatment," said Maria-Victoria Mateos, M.D., Ph.D., Hospital Universitario de Salamanca, who presented the results today. "For the first time in the front-line setting, we have long-term follow-up data, confirming that VMP results in a significantly longer overall survival than a standard of care, both overall and in patients who received subsequent therapy. This supports the addition of VELCADE to MP in the front line setting, rather than the use of MP followed by novel agents.”
The VISTA study is the largest Phase III registration trial to study long-term overall survival in previously untreated multiple myeloma patients. The VISTA trial enrolled 682 patients with previously untreated multiple myeloma ineligible for stem cell transplantation. At the interim analysis that demonstrated the superiority of VMP over MP, the benefit was seen across all efficacy endpoints, including overall survival. At this year's meeting, data with a median follow-up of 36.7 months were presented by Professor Mateos. In addition, a detailed analysis evaluated the impact of subsequent therapy on the overall survival results. The updated results included:
“These data further solidify the benefit of using VELCADE as initial therapy, as it provides
a long-term improvement in overall survival,” said Nancy Simonian, M.D., Chief Medical Officer, Millennium. “These data also demonstrate that the use of VELCADE upfront preserves options for subsequent therapy, including VELCADE.”
Patients in the VMP arm of the study received nine 6-week cycles of VELCADE at 1.3 mg/m2 (days 1, 4, 8, 11, 22, 25, 29 and 32 in cycles 1 through 4 and days 1, 8, 22 and 29 in cycles 5 through 9) with melphalan 9 mg/m2 and prednisone 60 mg/m2 (days 1 through 4 in cycles 1 through 9), or melphalan plus prednisone, in the same dose and schedule administered to the patients in the VMP arm. Patients remained on VMP therapy for a median of 46 weeks (eight cycles) out of the planned nine cycles versus 39 weeks (seven cycles) with melphalan and prednisone.
About Multiple Myeloma
Multiple myeloma is the second most common hematologic malignancy. In the U.S., more than 50,000 individuals have MM and 20,000 new cases are diagnosed each year. Worldwide there are approximately 74,000 new cases and over 45,000 deaths annually.
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, and has a robust clinical development pipeline of product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. in May, 2008. The Company's research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, www.millennium.com
VELCADE is co-developed by Millennium Pharmaceuticals, Inc. and Ortho Biotech Oncology Research & Development, a unit of Johnson & Johnson Pharmaceutical Research & Development, L.L.C., and approved worldwide. 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. VELCADE is currently approved in more than 87 countries worldwide.
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® [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 ‰¥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%).
In the Phase 3 VELCADE + melphalan and prednisone study, the safety profile of VELCADE in combination with melphalan/prednisone is consistent with the known safety profiles of both VELCADE and melphalan/prednisone. 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%).
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).
Editors' Note: This press release is also available under the Media section of the Company's website at: www.millennium.com
1 VELCADE as Initial Standard Therapy in multiple myeloma: Assessment with melphalan and prednisone
Posted: December 2009