Regulatory Decision Summary for Darzalex

Multiple myeloma (MM) is a progressive and life-threatening disease. Despite the available treatments, these patients eventually relapsed or become refractory to treatments. Therefore, there remains a high unmet medical need for these patients. The pivotal study MMY3003 conducted in MM patients who had received at least one prior therapy demonstrated a statistically significant and a substantial improvement in PFS (63% reduction in the risk of progression or death) of Darzalex in combination with lenalidomide and dexamethasone (DRd) over lenalidomide and dexamethasone alone (Rd). These results were consistent among subgroups and were also supported by a higher ORR in the DRd arm (91.3%) compared to the Rd arm (74.6%). The duration of response was not reached in the DRd arm and was 17.4 months in the Rd arm. With a median follow-up of 13.5 months, 75 deaths were observed (30 in the DRd arm and 45 in the Rd arm).

Study MMY3004 demonstrated superior efficacy of Darzalex in combination with bortezomib and dexamethasone (DVd) compared to bortezomib and dexamethasone (Vd) for MM patients who had received at least one prior therapy. DVd therapy resulted in a substantial improvement in PFS with a 61% reduction in the risk of death or disease progression over Vd therapy. The PFS benefit was consistent among patient subgroups and was supported by a higher ORR in the DVd arm (79.3%) compared to the Vd arm (59.9%). With a median follow-up of 7.4 months, 65 deaths were observed (29 in the DVd arm and 36 in the Vd arm).

As expected, there were increased safety findings in patients treated with Darzalex compared with patients who only received lenalidomide with dexamethasone alone, or bortezomib with dexamethasone alone. The most important safety findings associated with Darzalex were infusion-related reactions, infections including upper respiratory tract infections, and hematology abnormalities (neutropenia, thrombocytopenia, lymphopenia and anemia). Other risks associated with Darzalex were diarrhea, constipation, nausea, fatigue, pyrexia, cough, dyspnea, muscle spasms, insomnia, cardiac disorders including atrial fibrillation, and/or second primary malignancy. Fatal cases of infections occurred more frequently in patients treated with Darzalex in combination with lenalidomide and dexamethasone.

In view of the statistically significant and clinically meaningful PFS benefit associated with an ORR improvement in the context of this recurrent disease and a manageable safety profile, the overall risk benefit profile of Darzalex in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, is favourable for the treatment of patients with multiple myeloma who have received at least one prior therapy.