The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Sanofi’s Sarclisa (isatuximab) in combination with Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone (VRd) for the treatment of newly diagnosed multiple myeloma (MM) in adult patients who are not eligible for autologous stem cell transplant.
This positive opinion marks a significant step forward in addressing a critical care gap for patients with newly diagnosed MM who cannot undergo stem cell transplantation. Multiple myeloma is the second most common blood cancer, with a five-year survival rate of approximately 52% for newly diagnosed patients, highlighting the need for more effective front-line therapies.
IMROZ Trial Results
The CHMP's recommendation was primarily based on the results of the global Phase III IMROZ trial. The study evaluated the efficacy and safety of Sarclisa combined with VRd compared to VRd alone in this patient population. The trial met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS) with the Sarclisa-VRd combination.
The IMROZ study showed a 40% reduction in the risk of disease progression or death compared to VRd alone. Median progression-free survival (PFS) with the Sarclisa/VRd combination was not reached after a median follow up of 59.7 months versus 54.3 months with Vrd, and the estimated PFS at 60 months was 63.2% for patients treated with Sarclisa/VRd compared to 45.2% for those receiving VRd.
Mechanism of Action and Clinical Significance
Sarclisa is a monoclonal antibody designed to bind to the CD38 protein, which is highly expressed on multiple myeloma cells. By targeting CD38, Sarclisa induces distinct anti-tumor activity, including apoptosis and immunomodulatory effects. The drug has already been approved in over 50 countries for certain adult patients with relapsed or refractory MM.
Olivier Nataf, global head of oncology at Sanofi, noted the significant unmet need in the front-line setting for transplant-ineligible patients. "With this decision, the 27 countries in the EU will have access to a potentially transformative new combination regimen, marking a significant step forward in our mission to make a meaningful difference in MM treatment."
Safety Profile
The safety profile of Sarclisa, when combined with VRd, was found to be consistent with previous findings, with no new safety concerns identified in the IMROZ trial. This is an important consideration for patients who may be less tolerant of aggressive treatments.
Future Directions
Sanofi is also exploring a subcutaneous administration method for Sarclisa in clinical trials, which could offer a more convenient option for patients. The company is committed to furthering its clinical development program, which includes a range of Phase II and Phase III trials for multiple potential indications.
