New Data on Market-Leading VELCADE(R) (Bortezomib) for Injection Further Strengthen Role in Previously Treated Multiple Myeloma
Monday June 4, 3:01 pm ET
- Positive data on subcutaneous administration show potential for new option to improve convenience for patients
- Recently FDA-approved VELCADE + DOXIL(R) (pegylated liposomal doxorubicin) combination significantly extends time to disease progression and is recognized as Best of ASCO -
CHICAGO, June 4 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM - News) today announced the presentation of positive data for VELCADE, the market-leading therapy for patients with multiple myeloma (MM) who have received at least one prior therapy. These data include results from a Phase II trial for subcutaneous (SC) administration of VELCADE, a new option under evaluation. Results were also presented from the international Phase III trial of VELCADE + DOXIL, which served as the basis for the recent U.S. approval of the combination and showed significant improvement in time to disease progression compared to VELCADE alone, the current standard of care. The VELCADE + DOXIL abstract was selected by the Best of the American Society of Clinical Oncology (ASCO) Program Committee as one of the premier abstracts at the 43rd Annual Meeting in Chicago.
"We and our partner Johnson & Johnson Pharmaceutical Research and Development L.L.C. continue to develop new clinical data that reinforce the role of VELCADE as the U.S. market-leading therapy in previously treated multiple myeloma," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "These data demonstrate that VELCADE in combination with another active agent can further strengthen the unparalleled impact of VELCADE. We are aggressively pursuing development of a subcutaneous delivery form to broaden alternatives for patients who prefer to receive VELCADE treatment at home."
Prospective Comparison of Subcutaneous to Intravenous Administration of Bortezomib in Patients with Multiple Myeloma: Pharmacokinetics, Efficacy and Toxicity (Abstract #8046)
This randomized trial evaluated the pharmacokinetics/pharmacodynamics (PK/PD), toxicity and response rate of VELCADE in patients treated with either an SC or intravenous (IV) administration option. Results were presented by Philippe Moreau, M.D., University Hospital Hotel-Dieu and showed:
-- Similar bioavailability for the two routes of administration
-- Similar safety and tolerability profiles for the two routes of administration with a trend favoring the SC route as evidenced by fewer patients in this group discontinuing therapy
-- Identical response rates for the two routes of administration with both groups of patients achieving an overall response rate (complete and partial response) of 42 percent
The trial included 24 patients who were randomized to receive either SC or IV injections of VELCADE at the standard dose of 1.3 mg/m2 twice weekly for two weeks on days 1, 4, 8 and 11 with one week rest for up to eight cycles. Blood samples were taken on days 1 and 11 to measure PK by plasma Cmax (maximum plasma concentration), AUC (area under plasma concentration-time curve) and Tmax (time to Cmax) values and to measure PD by AUE (area under effect curve) and Emax (maximum effect) values. Patients received a median number of six and five cycles in the IV and SC groups, respectively.
Effect of the Combination of Pegylated Liposomal Doxorubicin and Bortezomib on Time to Progression (TTP) and Overall Survival of Patients With Relapsed/Refractory Multiple Myeloma Compared With Bortezomib Alone (Abstract #8002)
"The combination of VELCADE + DOXIL is highly active, with the time to disease progression the strongest in any U.S.-approved label for this patient population," said Jean-Luc Harousseau, M.D., University Hospital Hotel-Dieu. "Based on the Phase II trial, which showed a median overall survival greater than 38 months, we believe that the strong efficacy of the combination in the Phase III trial will extend to a substantial improvement in overall survival as well."
The Phase III study compared the efficacy and safety of the combination of VELCADE + DOXIL to VELCADE monotherapy, the standard of care in patients with previously treated MM. Results were presented by Dr. Harousseau and showed:
-- A survival advantage was observed for the VELCADE + DOXIL combination, after approximately 20 percent of events occurred (p<0.05, hazard ratio=1.406, 95 percent confidence interval [1.002; 1.972])
-- Median time to progression (TTP) of 9.3 months for the combination, a 43 percent, highly statistically significant reduction in risk of disease progression over the control arm (p<0.00001)
-- A predictable safety profile consistent with the known toxicities of the two agents, including thrombocytopenia, neutropenia and anemia
The trial included 646 patients who had received at least one prior therapy. Patients were randomized in a one-to-one ratio, with 322 patients receiving VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11 of the 21-day cycle and 324 patients receiving the same dose and schedule of VELCADE with the addition of DOXIL at 30 mg/m2 given on day 4 of each cycle. Patients were treated for up to eight cycles. The primary endpoint of the study was TTP as defined by the interval between the date of randomization and the date of disease progression, including relapse after complete response or death due to disease progression. In both arms, 66 percent of patients had received more than two prior therapies before entering the trial. Responses were assessed by European Group for Blood and Marrow Transplantation (EBMT) criteria. |
