Velcade Report

"VELCADE has been successfully combined with standard and emerging multiple myeloma therapies and has achieved some of the highest overall response rates in the front-line setting, ranging from 67 to 95 percent," said David Schenkein, M.D., senior vice president, clinical research, Millennium. "As the only single-agent therapy with a significant survival advantage in relapsed multiple myeloma, new data presented at ASCO also demonstrated a survival advantage in patients with poor prognostic factors, such as chromosome 13 deletion."

VELCADE is approved in the U.S. for the treatment of patients who have received at least one prior therapy. To date, more than 12,000 patients have been treated with VELCADE. Clinical studies in the front-line setting were the subject of several presentations at the recent International Myeloma Workshop in Sydney, Australia. The results of five studies indicated VELCADE based regimens induced high response rates in MM patients and toxicities were manageable. These studies were the basis of three large, multicenter international, randomized phase III trials, and are part of a broad co- development program between Millennium and Johnson & Johnson Pharmaceutical Research & Development.

VELCADE® (bortezomib) for Injection in Newly Diagnosed MM Patients (Abstract 6653) Interim results from the front-line multicenter phase II, IFM cooperative group trial, led by Jean-Luc Harousseau, M.D., of the Hospital Hotel-Dieu in France, assessed the efficacy and safety of VELCADE in combination with standard therapy dexamethasone as an induction treatment prior to autologous stem cell transplant. Patients received four treatment cycles followed by stem cell harvest and autologous stem cell transplant. Results reported for 48 patients include:

Ÿ         Overall response rate was 67 percent, including complete and partial responses with complete response rates of 21 percent and very good partial responses (90 percent reduction in M-protein) in an additional 10 percent of patients;

Ÿ         Stem cell harvest was successful in 100 percent of patients who  proceeded to autologous stem cell collection;

Ÿ         Stem cell harvest was sufficient to support single autologous stem cell transplant in 100 percent of patients who went on to transplant and overall responses were improved post-transplant;

Ÿ         Overall response rate after single transplant was 90 percent with 33 percent complete response and 21 percent very good partial response, comparable to results after tandem transplants; and

Ÿ         Treatment was well tolerated and most frequent toxicities included gastrointestinal events, peripheral neuropathy, fatigue, skin toxicity, infection and hematologic toxicities.

"The results from this study and other studies assessing VELCADE based regimens for induction therapy prior to transplant in the front-line setting have shown patients achieve high complete and very good partial responses and were able to undergo transplant successfully," said Professor Harousseau. "Longer survival has previously been associated with these quality responses and may offer new hope to newly-diagnosed multiple myeloma patients."

VELCADE in Relapsed High-Risk MM Patients

Additional analyses were reported at ASCO from the multicenter phase III APEX study which compared VELCADE to high-dose dexamethasone under the direction of Ken Anderson, M.D., and Paul Richardson, M.D., of the Dana Farber Cancer Institute of Boston, MA. These new subset analyses showed significantly improved outcomes and quality of life in relapsed patients. Results include:

    -- Patients with Chromosomal 13 Deletion Abnormality (Abstract 6501)

Ÿ         The survival benefit was maintained despite the presence of a chromosomal 13 deletion, a poor prognostic factor associated with inferior outcomes.

    -- High-Risk and Elderly (65 years or older) Patients (Abstract 6533)

Ÿ         Median time to progression was significantly improved in the elderly and in those patients who had greater than one prior therapy, B2M >2.5 mg/L (blood protein associated with disease severity) and who were refractory to prior treatment;

Ÿ         Response rates were significantly higher in the elderly and those patients who had greater than one prior therapy, B2M >2.5 mg/L and who were refractory to prior treatment.

    -- Quality of Life Assessment (Abstract 6535)

Ÿ         Significantly better outcomes were demonstrated in global health and physical role, cognitive and emotional functioning and symptoms of total neurotoxicity, nausea, dyspnea, sleep, diarrhea and financial impact.

"The new analysis of patients with a chromosome 13 deletion demonstrated survival outcomes for VELCADE treated patients is independent of the genetic abnormality," said Sundar Jagannath, M.D., St. Vincent's Comprehensive Cancer Center, New York, NY. "This is the first time a therapy has overcome this poor prognostic indicator."