Sarclisa Approved in US as First Anti-CD38 Therapy with Standard Care for Newly Diagnosed Multiple Myeloma Non-Transplant Patients

The US Food and Drug Administration (FDA) has approved the use of Sarclisa (isatuximab) in conjunction with bortezomib, lenalidomide, and dexamethasone (VRd) as an initial treatment for adults with newly diagnosed multiple myeloma (NDMM) who are not suitable candidates for autologous stem cell transplant (ASCT). Sarclisa is the first anti-CD38 therapy combined with standard VRd to significantly lessen disease progression or death by 40% compared to VRd alone for these patients.

Dr. Thomas Martin from the Helen Diller Family Comprehensive Cancer Center at the University of California San Francisco highlighted that multiple myeloma is predominantly diagnosed in individuals aged 65 and older. However, treatment options for this demographic are limited due to age-related factors, frailty, and co-morbidities. He emphasized the critical need for new treatments that can enhance the standard of care. The FDA's approval of the IMROZ regimen, which combines isatuximab with VRd, marks a significant advancement for this vulnerable group and the wider multiple myeloma community.

This approval is the third indication for Sarclisa in the United States and the first for newly diagnosed patients. The FDA reviewed Sarclisa under Priority Review, a designation for medicines that might offer major improvements in efficacy or safety in treating severe conditions. Sarclisa is already approved in over 50 countries for treating relapsed or refractory disease.

Brian Foard, Executive Vice President and Head of Specialty Care at Sanofi, noted the significant progress Sarclisa has made since its launch in 2020. He remarked that the FDA's decision represents an important milestone and broadens the reach of this potentially transformative therapy to a larger patient population. With this approval, physicians now have a new option to slow disease progression in adults with newly diagnosed multiple myeloma who are ineligible for transplant in the US.

The FDA's approval is based on the IMROZ phase 3 study, presented at the American Society of Clinical Oncology (ASCO) 2024 annual meeting and published in The New England Journal of Medicine. IMROZ is the first global phase 3 study to show that an anti-CD38 monoclonal antibody combined with standard VRd significantly improves progression-free survival (PFS) compared to VRd alone. The study revealed that Sarclisa-VRd followed by Sarclisa-Rd significantly reduced the risk of disease recurrence or death by 40% compared to VRd followed by Rd in patients with NDMM who are not ASCT candidates. After a median follow-up of nearly 60 months, the median PFS for the Sarclisa-VRd group was not reached, compared to 54.3 months for the VRd group. The estimated PFS rate at 60 months was 63.2% for the Sarclisa-VRd group versus 45.2% for the VRd group.

Sarclisa-VRd also met several secondary endpoints, showing deep responses in patients. The safety and tolerability of Sarclisa in the IMROZ study were consistent with its known safety profile, with no new safety signals observed. The most common adverse reactions included upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reactions, insomnia, and COVID-19. Additionally, common hematologic laboratory abnormalities included decreased hemoglobin, leukocytes, lymphocytes, platelets, and neutrophils. Serious adverse reactions occurred in 71% of patients receiving the Sarclisa combination therapy, with pneumonia being the most frequent serious adverse reaction.

Sanofi is continuing to advance Sarclisa through a clinical development program, which includes several phase 2 and phase 3 studies across the multiple myeloma treatment continuum. The company is also exploring a subcutaneous administration method for Sarclisa in clinical trials. The safety and efficacy of Sarclisa have not been evaluated by any regulatory authority outside of its approved indications and methods of delivery.

Sarclisa binds to a specific epitope on the CD38 receptor on multiple myeloma cells, inducing antitumor activity through various mechanisms, including programmed tumor cell death and immunomodulatory activity. CD38 is highly expressed on the surface of multiple myeloma cells, making it a target for antibody-based treatments like Sarclisa.

Sarclisa is approved in over 50 countries for use with pomalidomide and dexamethasone for relapsed refractory multiple myeloma (RRMM) patients who have received at least two prior therapies. It is also approved for use with carfilzomib and dexamethasone for RRMM patients who have received one to three prior lines of therapy. Sanofi remains dedicated to advancing Sarclisa through various clinical studies to bring this treatment to more patients and to investigate new combinations and methods of administration.

Multiple myeloma is the second most common hematologic malignancy, affecting over 130,000 patients in the United States. Despite available treatments, multiple myeloma remains an incurable malignancy with a five-year survival rate of approximately 52% for newly diagnosed patients. Most patients with newly diagnosed multiple myeloma are not eligible for transplant, highlighting the need for new frontline therapeutic options.