The FDA has approved Sarclisa (isatuximab) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) as a first-line treatment option for adult patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for autologous stem cell transplant (ASCT). This decision, based on the IMROZ phase 3 study, marks a significant advancement in the treatment landscape for this patient population. Sarclisa is the first anti-CD38 therapy approved in combination with the standard-of-care VRd regimen, offering a new and effective treatment option. The approval was granted after the IMROZ trial demonstrated a significant reduction in the risk of disease progression or death compared to VRd alone. The study's findings, presented at the American Society of Clinical Oncology (ASCO) 2024 annual meeting and published in The New England Journal of Medicine, highlight the potential of this quadruplet therapy to improve outcomes for patients with NDMM.
IMROZ Trial Results
The IMROZ trial, a phase 3 study, involved 446 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized to receive either Sarclisa in combination with VRd or VRd alone. The primary endpoint was progression-free survival (PFS). Key findings from the trial include:
- A 40% reduction in the risk of disease progression or death with Sarclisa plus VRd (HR 0.60; 95% CI: 0.44 to 0.81, p=0.0009).
- Median PFS with the Sarclisa-VRd combination was not reached versus 54.3 months with VRd.
- The estimated PFS rate at 60 months was 63.2% for patients treated with Sarclisa-VRd versus 45.2% for VRd.
- Approximately 74.7% of patients treated with Sarclisa-VRd achieved a complete response (CR) or better compared to 64.1% of patients taking VRd (OR 1.7; 95% CI: 1.097-2.5; p=0.0160).
- More than half (55.5%) of patients treated with Sarclisa-VRd achieved MRD negative CR compared to 40.9% of patients taking VRd (OR 1.8; 95% CI: 1.229-2.646; p=0.0026).
Safety and Tolerability
The safety and tolerability profile of Sarclisa in the IMROZ study was consistent with the established safety profiles of Sarclisa and VRd. Common adverse reactions included upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, and pneumonia. Serious adverse reactions occurred in 71% of patients receiving Sarclisa combination therapy, with pneumonia being the most frequent serious adverse reaction (30%).
Expert Commentary
Thomas Martin M.D., Clinical Professor of Medicine at the University of California San Francisco, noted the significance of the approval for a vulnerable patient population: "Multiple myeloma is most frequently diagnosed in patients 65 years and older, yet the options for treatment in this population are limited due to a combination of age, frailty, and co-morbidities. The significant clinical benefit and improvements in progression-free survival demonstrated by the IMROZ regimen of isatuximab plus VRd versus VRd alone make today’s approval an important moment for this vulnerable patient population and the larger multiple myeloma community."
Sarclisa's Expanding Role in Multiple Myeloma
This approval marks the third indication for Sarclisa in the US and the first approved indication in newly diagnosed patients. Sarclisa is also approved in more than 50 countries across two indications for the treatment of people with relapsed or refractory disease. Sanofi continues to advance Sarclisa as part of a patient-centric clinical development program, which includes several phase 2 and phase 3 studies across the MM treatment continuum. The company is also evaluating a subcutaneous administration method for Sarclisa in clinical studies.
