Sanofi Plans BLA Submission for Isatuximab in Relapsed/Refractory Multiple Myeloma Based on ICARIA-MM Phase III Data

On June 2, Sanofi announced at the ASCO 2019 conference that its CD38 monoclonal antibody drug isatuximab met the primary endpoint of improving progression-free survival (PFS) in the pivotal Phase III ICARIA-MM study involving patients with relapsed/refractory multiple myeloma. Sanofi plans to submit a marketing application for isatuximab to regulatory authorities by the end of this year based on these study results.

The ICARIA-MM study enrolled 307 patients with relapsed and refractory multiple myeloma who had previously received more than two therapies, including lenalidomide and/or a proteasome inhibitor, across 96 centers in 24 countries. Patients were randomized to receive either standard treatment (pomalidomide plus low-dose dexamethasone) or standard treatment plus isatuximab.

The results showed that isatuximab plus pomalidomide and dexamethasone prolonged progression-free survival (PFS) by 5 months compared with pomalidomide and dexamethasone alone (11.53 vs. 6.47 months), reduced the risk of disease progression and death by 40%, and significantly improved the overall response rate (ORR) (60% vs. 35%). Furthermore, the time to next treatment was significantly prolonged (immature vs. 9.1 months).

Regarding safety, the proportions of patients experiencing grade ≥3 adverse events were 86.8% in the isatuximab plus pomalidomide and dexamethasone group and 70.5% in the pomalidomide and dexamethasone group. The proportions of patients discontinuing treatment due to adverse events were 7.2% and 12.8%, respectively, and the proportions of patients dying due to adverse events were 7.9% and 9.4%, respectively. The incidence rates of grade ≥3 infections were 42.8% and 30.2%, respectively. The incidence rates of grade ≥3 neutropenia were 84.9% and 70.1%, respectively.

Johnson & Johnson’s Darzalex (daratumumab) is currently the only marketed CD38 monoclonal antibody; it was approved in November 2015, and its global sales reached $2.025 billion in 2018.

Original Title: Isatuximab for Relapsed/Refractory Multiple Myeloma Reduces Risk of Progression or Death by 40%