The Food and Drug Administration has approved a subcutaneous formulation of bortezomib, which will join the intravenous formulation as treatment for multiple myeloma and mantle cell lymphoma after at least one prior therapy, according to its manufacturer, Millennium: The Takeda Oncology Co.
Bortezomib is a proteasome inhibitor marketed as Velcade; the intravenous formulation was approved in 2003.
Approval of the subcutaneous formulation was based on a randomized, phase III open label noninferiority international study of patients with relapsed multiple myeloma, who had not received bortezomib previously. The study compared the overall response rate (ORR) after four treatment cycles in those treated with the subcutaneous formulation (145) and those treated with the IV formulation (73 patients); noninferiority was defined as retaining 60% of the IV treatment effect. After four cycles, the ORR was 43% among those on the subcutaneous formulation and 42% among those on the IV formulation. These results were published in May (Lancet Oncol. 2011;12:431-40).
Overall, the safety profile for the two arms was similar except for some serious adverse events, including peripheral neuropathy (PN): The rate of PN that was grade 3 or greater was 6% among those on the subcutaneous formulation, compared with 16% among those on the IV formulation, a significant difference. The rate of PN of any grade was also lower among those on the subcutaneous formulation (38% vs. 53%).
Other adverse events that were grade 3 and greater that were at least 5% higher among those on the IV formulation on were thrombocytopenia (6% vs. 16%), thrombocytopenia (13% vs. 19%), and neuralgia (3% vs. 9%).
A contraindication against intrathecal administration of bortezomib has been added to the label, because of fatal events that have resulted from inadvertent intrathecal administration of the drug.
The study was funded by Johnson & Johnson Pharmaceutical Research and Development and Millennium Pharmaceuticals.