Millennium Pharmaceuticals, Inc. announced results of a study that showed Velcade in combination with melphalan and prednisone (V-MP) appeared significantly superior to melphalan and prednisone (MP) alone in treating elderly patients with newly diagnosed multiple myeloma (MM) who were ineligible for stem cell transplantation.

The multi-center, phase I/II study evaluating the safety and efficacy of Velcade based therapy demonstrated an overall response rate of 89 per cent, including a high complete and near complete response rate of 43 per cent. This compared favourably to historical control data for MP, a widely used therapy that rarely induces complete response. Complete response is considered an important prognostic factor for survival. The study was pre-published online in the journal, Blood, First Edition, June 13, 2006.

"Approximately half of patients presenting with multiple myeloma are elderly and not eligible for transplantation. New treatments that produce very high complete responses and molecular remissions are desperately needed," said lead investigator Jesus San Miguel, Professor of Medicine at the University Hospital in Salamanca, Spain. "With only one cycle of V-MP, we achieved a higher response rate than our historical controls of six cycles of MP and the proportion and quality of completed responses increased with subsequent cycles."

The open-label, dose-escalation study evaluated the safety and efficacy of V-MP in 60 newly diagnosed multiple myeloma patients between 65 and 85 years old, with almost half of all patients (47 per cent) over 75 years old.

An analysis from the study demonstrated: Overall response rate of 89 per cent with 43 per cent of patients achieving complete (32 per cent) or near-complete (11 per cent) response; In complete responders, half were immunophenotypic remissions as analyzed by multiparameter flow cytometry (a highly sensitive method to identify molecules associated with malignant cells); 91 per cent were free of disease progression and event-free survival rate was 83 per cent compared to historical control data for MP of 66 per cent and 51 per cent; Median time to progression and overall survival not yet reached after a median follow-up of 16 months; Responses were independent of chromosomal abnormalities which generally predict for poorer outcomes; Treatment was well tolerated with a median of 42 weeks of treatment, a duration of more than 9 months. Common adverse events were gastrointestinal events, thrombocytopenia, neutropenia, fatigue and peripheral neuropathy.

"The complete responses and deep molecular remissions in this V-MP study have never been reported in this treatment setting, highlighting the potency of Velcade," said Robert Tepper, M.D., President, Research & Development, Millennium. "These results are similar to what you would expect to achieve in the transplant setting with a much more favourable safety profile."

The published study is the basis for an ongoing company-sponsored, phase III, international VISTA trial of Velcade in combination with V-MP versus MP alone in patients with newly diagnosed multiple myeloma that are not transplant candidates. The data are also consistent with results in this elderly population observed in a subgroup analysis of the phase III APEX trial, which investigated Velcade treatment in patients with relapsed MM and included patients aged 65 years and older. Velcade was found to be equally effective in elderly and younger patients -- the response rate did not differ substantially between the two groups. In addition, the overall incidence of adverse events was comparable across all age groups, indicating that Velcade is equally tolerated in elderly and younger patients. However, greater sensitivity in some older individuals cannot be ruled out.

Two additional, phase III, multi-center trials being conducted by international cooperative groups are evaluating Velcade based combinations in newly diagnosed patients who are eligible for transplantation. Collectively, these three front-line PHASE III studies are anticipated to enrol approximately 2,000 patients and interim results from one of these is expected by the end of the year.

MM is the second most common haematologic malignancy and although the disease is predominantly a cancer of the elderly (the average age of onset is 65 to 70 years of age), recent statistics indicate both increasing incidence and younger age of onset. In the US, more than 45,000 to 50,000 individuals have MM and over 15,000 new cases are diagnosed each year. Worldwide there are approximately 74,000 new cases and over 45,000 deaths annually.

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 observed throughout therapy, cardiac and pulmonary disorders, gastrointestinal adverse events, thrombocytopenia, neutropenia and tumour lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with Velcade.

Velcade is the market leader in relapsed multiple myeloma with over 44,000 patients treated worldwide, including clinical trials. Velcade 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 US; 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 approved in more than 65 countries worldwide. Velcade also is approved in the European Union as a treatment at first relapse.