The European Medicines Agency (EMA)'s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of Sarclisa (isatuximab), in combination with bortezomib, lenalidomide, and dexamethasone (VRd), for the treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT). This decision, if finalized by the EMA, could establish a new standard-of-care in the European Union for this patient population.
The positive CHMP opinion is based on data from the Phase 3 IMROZ study, a global trial evaluating Sarclisa in combination with VRd versus VRd alone. The IMROZ study, presented at the American Society of Clinical Oncology (ASCO) and the European Hematology Association (EHA) annual meetings in 2024, and published in The New England Journal of Medicine, demonstrated a statistically significant improvement in progression-free survival (PFS) for the Sarclisa combination. The safety and tolerability profile of Sarclisa observed in the study was consistent with the established profiles of both Sarclisa and VRd.
Clinical Significance of IMROZ Study
The IMROZ study is the first global Phase 3 trial to show that adding a CD38 monoclonal antibody to the standard-of-care VRd regimen significantly improves PFS in transplant-ineligible NDMM patients. This is particularly important as many patients with multiple myeloma are not eligible for ASCT due to age or comorbidities, leaving a significant unmet need for effective first-line therapies.
"The positive CHMP opinion is an important step forward for people with transplant-ineligible newly diagnosed multiple myeloma for whom effective front-line therapy may improve long-term outcomes," said Dietmar Berger, M.D., Ph.D., chief medical officer, global head of development at Sanofi. "If approved, this Sarclisa-based combination could establish a new standard-of-care treatment approach for patients in the EU, helping to address a critical care gap in multiple myeloma treatment, and reinforcing Sarclisa’s potential as the anti-CD38 therapy of choice."
Sarclisa: Mechanism of Action
Sarclisa (isatuximab) is a CD38 monoclonal antibody designed to bind to a specific epitope on the CD38 receptor on multiple myeloma cells, inducing direct antitumor activity. It works through multiple mechanisms of action, including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a prime target for antibody-based therapeutics.
Regulatory Landscape and Existing Approvals
In September 2024, the US Food and Drug Administration (FDA) approved Sarclisa in combination with VRd for the treatment of adult patients with NDMM who are not eligible for ASCT, representing the first global approval for Sarclisa in the first-line setting. The FDA also granted orphan drug exclusivity for Sarclisa in this indication.
Sarclisa is currently approved in more than 50 countries, including the US and EU, for the treatment of certain adult patients with relapsed or refractory MM (RRMM). In Europe, Sarclisa is approved in combination with pomalidomide and dexamethasone for RRMM patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and who progressed on their last therapy. It is also approved in combination with carfilzomib and dexamethasone for patients with RRMM who have received at least one prior therapy.
Sanofi is continuing to advance Sarclisa through a comprehensive clinical development program, including several Phase 2 and Phase 3 studies across the MM treatment continuum, spanning six potential indications. The company is also evaluating a subcutaneous administration method for Sarclisa in clinical studies.
