The US Food and Drug Administration (FDA) approved Takeda's bortezomib (Velcade) injection for new indication -to treat patients with previously untreated multiple myeloma (MM). The Company's co-development partner, Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) also has filed a corresponding application with the European Medicines Evaluation Agency (EMEA).
"This comes as wonderful news for patients. The VISTA1 trial showed 30% complete remission rate with bortezomib compared to 4% for the control arm. Importantly, patients treated with bortezomib also experienced a survival benefit," said Paul Richardson, M.D., a senior investigator for the study and Clinical Director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute.
"We are excited for patients with previously untreated multiple myeloma, who now can benefit from VELCADE, including its ability to deliver a significant increase in overall survival. VELCADE treatment also is available for multiple myeloma patients in the second- and third-line settings, where it already is approved," said Deborah Dunsire, M.D., President and CEO, Millennium Pharmaceuticals, The Takeda Oncology Company.
The current approval was based on an international, multicenter, open label, active-control trial in previously untreated patients with symptomatic multiple myeloma. Patients were randomized to receive either nine 6 week cycles of oral melphalan (M) plus prednisone (P) or MP plus VELCADE. Patients received M (9 mg/m2) plus P (60 mg/m2) daily for four days every 6 weeks or the same MP schedule with bortezomib (1.3 mg/m2) IV on days 1, 4, 8, 11, 22, 25, 29 and 32 of every 6 week cycle for 4 cycles then once weekly for 4 weeks on days 1, 8, 22 and 29 of every 6 week cycle for 5 additional cycles. Antiviral prophylaxis was recommended for patients on the VELCADE study arm. Time-to-progression (TTP) was the primary efficacy endpoint. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were secondary endpoints. A total of 682 patients were randomized: 338 to receive MP and 344 to receive the combination of bortezomib plus MP. The median age of patients for both groups was 71 years. Demographics and baseline disease characteristics were similar between the two groups.
The safety profile of VELCADE in combination with MP is consistent with the known safety profiles of both VELCADE and MP.
In VISTA, the most commonly reported adverse events for VELCADE in combination with MP vs MP, respectively, were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%), nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%), anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs 1%), leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%), fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%), asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs 10%), rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%), dizziness (16% vs 11%), dyspnea (15% vs 13%), headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal pain (14% vs 7%), paresthesia (13% vs 4%), herpes zoster (13% vs 4%), bronchitis (13% vs 8%), hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension (12% vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs 10%), arthralgia (11% vs 15%) and pruritus (10% vs 5%).