Subcutaneous Isatuximab Meets Primary End Points in Phase 3 Study for MM

A subcutaneous (SC) formulation of isatuximab (Sarclisa, Sanofi) was found to be just as effective as the intravenous version of the drug in treating multiple myeloma, which could pave the way for an approval that would remove a major advantage for a competitor.

In topline results announced today, Sanofi officials said the SC version of the anti-CD38 monoclonal antibody met coprimary end points in the phase 3 IRAKLIA study, demonstrating noninferiority compared with isatuximab IV. According to the statement, IRAKLIA is the first global phase 3 study to evaluate SC administration of a cancer therapy via an on-body delivery system (OBDS). FDA has approved such systems for other treatments, which are designed to save time, allow freedom of movement during administration, and improve quality of life.

“The consistent overall response rate and comparable efficacy and safety profile observed in the IRAKLIA study for subcutaneous [isatuximab] represent an exciting advancement, offering insight into a potential new administration option for patients,” principal investigator Sikander Ailawadhi, MD, professor of medicine, Division of Hematology/Oncology at Mayo Clinic Florida, said in the statement. The results “support the potential of an on-body delivery system to help ease the delivery of a new formulation without impacting patient outcomes.”

SC administration has gained ground over IV administration of cancer therapies over the past decade, for reasons of patient convenience, lower cost, and reduced risk of infection. Another anti-CD38 monoclonal antibody, daratumumab (Darzalex, Johnson & Johnson), is already available in an SC formulation.

Isatuximab binds to a specific epitope on the CD38 receptor on myeloma cells, producing a distinct antitumor response. It works through multiple pathways, including direct apoptosis, crosslinking of CD38 and CD16, and by sensitizing T cells against CD38-positive cells. Daratumumab has some mechanisms of action that are similar to isatuximab but not direct apoptosis.

Both isatuximab and daratumumab have been approved in combination with bortezomib, lenalidomide, and dexamethasone for patients newly diagnosed with multiple myeloma.

In the IRAKLIA study, investigators used an OBDS developed by Enable Injections, which gained approval for an on-body injector in October 2023 to deliver pegcetacoplan (Empaveli) for paroxysmal nocturnal hemoglobinuria (PNH). The product, called Enfuse, rapidly gained acceptance among patients that were currently taking pegcetacoplan and was prescribed to 90% of new users by February 2024.

In the trial involving patients with relapsed or refractory multiple myeloma, isatuximab was administered at a fixed SC dose via the Enfuse OBDS in combination with pomalidomide and dexamethasone. Sanofi officials said the study met coprimary end points of noninferior objective response rate and observed observed concentration before dosing at a steady state, compared with IV isatuximab at a weight-based dose in combination with pomalidomide and dexamethasone.

Key secondary end points, which included very good partial response (VGPR), and incidence rate of infusion reactions were also achieved. Full results of the ongoing study will be presented at a future medical meeting. Additional studies evaluating SC formulations of isatuximab across different combinations and lines of therapy are ongoing. According to the statement, regulatory submissions in the United States and Europe are anticipated in the first half of this year.