FDA Approves Velcade for Myeloma

June 1, 2003

WASHINGTON-The FDA has approved Millennium Pharmaceuticals’ Velcade (bortezomib) injection for patients with multiple myeloma that has relapsed after two prior treatments and has shown resistance to the last treatment. Velcade was granted priority review by the FDA on March 10, 2003, and was approved approximately 2 months later. It has been just 4½ years from the first human dose to FDA approval.

WASHINGTON—The FDA has approved Millennium Pharmaceuticals’ Velcade (bortezomib) injection for patients with multiple myeloma that has relapsed after two prior treatments and has shown resistance to the last treatment. Velcade was granted priority review by the FDA on March 10, 2003, and was approved approximately 2 months later. It has been just 4½ years from the first human dose to FDA approval.

Proteasome Inhibitor

Velcade is the first in a new class of anticancer agents known as proteasome inhibitors. The proteasome is an enzyme complex that exists in all cells and plays an important role in degrading proteins that control the cell cycle and cellular processes. By blocking the proteasome, Velcade disrupts numerous biologic pathways, including those related to the growth and survival of cancer cells.

"Millennium was established with the goal of using innovative science to develop novel products that would address the unmet medical needs of patients," said Mark Levin, chief executive officer and chairperson of Millennium. "Our success in bringing Velcade to patients so rapidly reflects the high level of collaboration among many partners, both internally and externally. Moving forward, Millennium will continue its mission of developing breakthrough products that make a difference in patients’ lives."

FDA evaluated the safety and efficacy of Velcade based on the phase II open-label single-arm SUMMIT study of 202 patients with relapsed and refractory multiple myeloma who had received at least two prior therapies (median, six). Patients had advanced disease, with 91% refractory to their most recent therapy prior to study entry.

Out of 188 patients evaluated for response, 27.7% showed a response to Velcade, lasting a median of 1 year. Significantly, 17.6% of patients experienced a clinical remission by Southwest Oncology Group (SWOG) criteria. Median survival was 16 months (range, less than 1 month to more than 18 months). The smaller CREST trial in 54 patients with relapsed multiple myeloma showed similar response rates. [See ONI February 2003, page 2.]

As of yet, there are no controlled trials of Velcade demonstrating clinical benefit such as improvement in survival. To address this issue, Millennium will perform additional studies after approval, including the completion of an ongoing study and an additional study comparing Velcade with standard therapy.

In the clinical studies, side effects were generally predictable and manageable. The most commonly reported adverse events were asthenic conditions (including fatigue, malaise, and weakness) 65%; nausea 64%; diarrhea 51%; decreased appetite 43%; constipation 43%; throm-bocytopenia 43%; peripheral neuropathy 37%; pyrexia 36%; vomiting 36%; and anemia 32%.

Fourteen percent of patients experienced at least one episode of grade 4 toxicity, with the most common being thrombocytopenia (3%) and neutropenia (3%).