FDA Approves Addition of Sustained Overall Survival Benefit to Label for Bortezomib

The Takeda Oncology Company announced that the US Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for bortezomib (Velcade), which expands the label to include long-term (median follow-up 36.7 months) overall survival (OS) data from the landmark VISTA trial (Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) and provides specific dosing recommendations for patients with hepatic impairment. The VISTA trial examined the use of bortezomib-based therapy in patients with previously untreated multiple myeloma (MM).

Key Data

The updated survival data, presented at the 51st Annual Meeting of the American Society of Hematology (ASH), confirmed the OS benefit observed at the original interim analysis that led to the front-line approval of bortezomib in MM in June 2008. This presentation of long-term follow-up data demonstrated that patients treated with VcMP (bortezomib, melphalan [Alkeran], and prednisone) continued to have significantly longer OS than those treated with MP (melphalan and prednisone) alone, a commonly used standard of care (P = .0008). These results translated into a 35% reduction in risk of death (hazard ratio = 0.65). The OS benefit of VcMP was observed despite the use of subsequent therapies at relapse, including bortezomib-based regimens.

“With multiple myeloma, there is a need for treatments that are clearly and unequivocally demonstrated to help patients live longer,” said Deborah Dunsire, MD, President and CEO, Millennium. “Velcade has been shown to provide a significant long-term survival benefit for patients, and we are thrilled to have this prolonged survival data added to the prescribing information.”

Starting Dose Adjustments

Takeda Oncology and FDA notified health-care professionals about revisions to the prescribing information for bortezomib, section 2.5, pertaining to patients with hepatic impairment at the start of bortezomib therapy. The changes also include new safety information on dose adjustment for patients with moderate to severe hepatic impairment in label section 5.11, stating: “Bortezomib is metabolized by liver enzymes. Bortezomib exposure is increased in patients with moderate or severe hepatic impairment; these patients should be treated with Velcade at reduced starting doses and closely monitored for toxicities.”