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Multiple Myeloma
Bortezomib Based Therapies may Become the New Standard of Care in Multiple Myeloma
By Millennium Pharmaceuticals
Apr 14, 2005, 20:57

Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM - News) today announced the presentation of positive clinical results for VELCADE in treating patients across the multiple myeloma (MM) treatment paradigm at the 10th Annual International Myeloma Workshop (IMW) in Sydney, Australia. Data regarding the use of VELCADE as a single agent and in combination with standard and emerging MM therapies were reported at the meeting.

Data presented provided evidence for the potential of VELCADE to induce higher response rates in earlier lines of therapy. Front- line studies of VELCADE were the highlight of several scientific sessions and showed very high response rates in previously untreated MM patients with manageable toxicities.

These studies were the basis for three large, multicenter, independent phase III studies. VELCADE is approved in the U.S. for the treatment of patients who have received at least one prior therapy.

"These front-line data suggest VELCADE may offer a new option for patients with multiple myeloma who have not yet been treated," said David Schenkein, M.D., senior vice president, clinical research, Millennium. "While VELCADE is the only single agent to demonstrate a statistical survival advantage in relapsed patients, the benefits in combination with other therapies confirm our belief that VELCADE based therapies can become the new standard of care in multiple myeloma."

The following is summary data from clinical studies of VELCADE presented at the IMW:

Front-line treatment in MM patients

In five investigator-initiated studies of VELCADE, two conducted by cancer cooperative groups, outcomes reported in combination with standard and emerging therapies included overall response rates of up to 95 percent and high complete and near complete response rates of up to 32 percent. A complete and near complete response rate of 57 percent was reported following single stem cell transplant preceded by induction with VELCADE/adriamycin/ dexamethasone (PAD). This response rate was similar to the complete response rate reported for tandem transplants. Front-line data showed patients were able to have successful stem cell harvest and transplantation after VELCADEŽ (bortezomib) for Injection.

In the front-line phase II Cancer and Leukemia Group B (CALGB) study, an initial report of responses in combination with liposomal doxorubicin showed complete and partial responses in 12 of 15 patients and no patients have progressed so far on study. Toxicities in this study were similar to the phase I study in which high response rates in relapsed or refractory patients prompted this front-line investigation. Other front-line combinations presented were VELCADE with high-dose dexamethasone and VELCADE with melphalan/prednisone. In these five studies overall, adverse events were found to be manageable and included gastrointestinal, asthenic conditions, hematologic, neurologic, skin toxicity, musculoskeletal and pyrexia. Positive results from these front-line studies have led to three large, international, randomized, phase III trials; two of which are being conducted by cooperative groups.

Second-line MM

In a phase III, multicenter trial comparing single agent VELCADE to high-dose dexamethasone, VELCADE demonstrated a 45 percent response rate, including an approximate 13 percent complete (6.25 percent) and near complete response rate (6.25 percent). Importantly, a longer duration of response and a statistically significant survival advantage were found in patients who had received only one prior therapy. Results showed that the probability of death with dexamethasone was 2.56 times that of VELCADE therapy. Side effects were as expected from prior experience with VELCADE, were manageable and peripheral neuropathy improved or reversed in nearly half of all patients. The most common adverse events reported in this study as related to VELCADE were gastrointestinal, neurologic, musculoskeletal and hematologic. These data were the basis of the recent FDA approval for VELCADE use in MM patients who have received at least one prior therapy.

Relapsed or refractory MM

Investigator-initiated studies demonstrated VELCADE was well tolerated and provided a high overall response rate as both a single agent and in combination with standard and emerging therapies, such as liposomal doxorubicin/thalidomide, melphalan and lenalidomide. In combination studies, the response rates of more than 60 percent in heavily pre-treated patients without additive toxicities showed the compatibility of VELCADE with these agents. Other combinations presented were VELCADE plus dexamethasone and VELCADE plus intravenous melphalan.

About Multiple Myeloma

MM is the second most common blood cancer 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 United States, more than 40,000 individuals have MM and over 14,000 new cases of the disease are diagnosed each year. Worldwide there are approximately 74,000 new cases and over 45,000 deaths due to multiple myeloma each year.

About VELCADEŽ (bortezomib) for Injection

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.

Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension, cardiac disorders, gastrointestinal adverse events, thrombocytopenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE.

In 331 patients who were treated with VELCADE 1.3 mg/m2 dose in the phase III APEX study, the most commonly reported adverse events were asthenic conditions (61%), diarrhea (57%), nausea (57%), constipation (42%), peripheral neuropathy (36%), vomiting (35%), pyrexia (35%), thrombocytopenia (35%), psychiatric disorders (35%) and anorexia and appetite decreased (34%). Fourteen percent of patients reported at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (4%), neutropenia (2%) and hypercalcemia (2%). A total of 144 patients on VELCADE (44%) reported serious adverse events (SAEs) during the study. The most commonly reported SAEs were pyrexia (6%), diarrhea (5%), dyspnea and pneumonia (4%) and vomiting (3%).

VELCADE is being co-developed by Millennium and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium is responsible for commercialization of VELCADE in the U.S.; Ortho Biotech and Janssen-Cilag are responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for Japan. VELCADE is approved in more than 40 countries worldwide including the U.S., European Union members, and a number of countries within Latin America and South-East Asia such as Argentina, China, Korea, Singapore and Thailand.

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