Regulatory Decision Summary for Darzalex

Authorization was based on a pivotal phase 3, randomized, controlled, open-label study comparing the safety and efficacy of Velcade (Bortezomib) Melphalan-Prednisone (VMP) to Daratumumab in combination with VMP (D-VMP), in subjects with previously untreated multiple myeloma who are ineligible for high-dose therapy. Seven hundred subjects were treated (346 D-VMP and 354 VMP). All subjects received up to 9 cycles of the VMP regimen (1 cycle = 6 weeks) with or without daratumumab. Subjects in the D-VMP arm continued to receive daratumumab every 4 weeks until documented disease progression, unacceptable toxicity, or study completion.

The primary efficacy endpoint was progression free survival (PFS). D-VMP therapy resulted in a substantial improvement in PFS with a 50% reduction in the risk of death or disease progression over VMP therapy alone. The PFS benefit was consistent among patient subgroups and was supported by a higher overall response rate (ORR) in the D-VMP arm (90.9%) compared to the VMP arm (73.9%). This included a complete or better response rate of 42.6% for D-VMP treated patients compared to 24.4% in the VMP group.

The safety findings were consistent with the previous observations of daratumumab and the VMP combination regimen. The most common adverse reactions (ADRs) reported in at least 25% of patients were infusion-related reactions, infections including upper respiratory tract infections, peripheral sensory neuropathy and hematology abnormalities (neutropenia, thrombocytopenia, anemia).

In view of the statistically significant and clinically meaningful PFS benefit associated with an ORR improvement compared with a current MM standard of care and a known, manageable safety profile, the overall risk-benefit assessment of daratumumab in combination with bortezomib, melphalan and prednisone, was determined to be favourable for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.