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FDA Grants Full Approval for Bortezomib in Relapsed Multiple Myeloma

CAMBRIDGE, Mass., March 25 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM - News) today announced the U.S. Food and Drug Administration (FDA) approved the Company's supplemental New Drug Application (sNDA) for VELCADE. This approval expands the label to include the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. VELCADE is the only drug therapy that has demonstrated a significant survival advantage as compared to a standard therapy in relapsed MM. Initial accelerated approval for relapsed and refractory MM was granted in May 2003. VELCADE is now fully approved in relapsed MM.

The approval was based on data from the randomized phase III APEX study that compared single-agent VELCADE to a traditional MM therapy, high-dose dexamethasone. The study demonstrated a significant survival advantage with VELCADE (p "We are thrilled that more patients will have access to VELCADE earlier in their treatment where VELCADE has shown a significant improvement over a standard therapy in improving survival and delaying disease progression," said David Schenkein, M.D., senior vice president, clinical research at Millennium. "Millennium is committed to making a difference in patients' lives and will continue, in partnership with Johnson & Johnson Pharmaceutical Research and Development L.L.C., to explore extensively the benefits of VELCADE across the multiple myeloma treatment paradigm as well as in other hematologic and solid tumors."

*Precise p-value cannot be rendered.

The approval of this supplementary filing comes approximately 22 months after the initial FDA approval of VELCADE® (bortezomib) for Injection. VELCADE, the first of a new class of medicines called proteasome inhibitors, is the first treatment in more than a decade to be approved for patients with multiple myeloma, a cancer of the blood.

APEX Study Results
The sNDA submission was based primarily upon the results of the phase III APEX study, which compared VELCADE to high-dose dexamethasone. The APEX trial enrolled 669 patients with relapsed multiple myeloma (patients had received one to three prior therapies) at 93 centers in North America, Europe and Israel. This study was conducted under the direction of Paul Richardson, M.D., clinical director, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute. The APEX trial was halted one year early after an independent data monitoring committee concluded the findings of a pre-specified interim analysis showed a statistically significant improvement in time-to-disease progression in favor of VELCADE.

In the overall study population, VELCADE was superior to high-dose dexamethasone based on time to progression (p -- Overall, 40 percent fewer patients died in the VELCADE arm relative to the dexamethasone arm;
-- Overall response rate of 38 percent with VELCADE, with a median duration of response of 8.0 months compared with a response rate of 18 percent, with a median duration of response of 5.6 months for dexamethasone;
-- Six percent of VELCADE patients had a complete response and 7 percent had a near complete response as compared to less than one percent each with dexamethasone; and
-- After a median of 8.3 months of follow-up, improvement in median time to progression was 78 percent with VELCADE relative to dexamethasone.

Among the 251 second-line multiple myeloma patients (those who had only one prior therapy), VELCADE was superior based on time to progression (p=0.0019), response rate (p=0.0035) and overall survival (p -- Overall, 55 percent fewer patients died in the VELCADE arm relative to the dexamethasone arm;
-- Overall response rate with VELCADE was 45 percent (median duration of response was 8.1 months) compared with 26 percent for dexamethasone (median duration of response 6.2 months); and
-- Six percent of VELCADE patients had a complete response and 6 percent had a near complete response as compared to two percent each with dexamethasone.

Adverse events on the VELCADE arm were predominantly grade one or two, were similar to those previously observed in other trials and were considered manageable by the investigators.

-- The most commonly reported adverse events were asthenic conditions, diarrhea, nausea, constipation, peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, psychiatric disorders and anorexia and appetite decreased; and
-- The most commonly reported serious adverse events were pyrexia, diarrhea, dyspnea, pneumonia and vomiting.

*Precise p-value cannot be rendered.

About VELCADE® (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%).

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).

Source: Millennium Pharmaceuticals, Inc.

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