SAR446523 Granted Orphan Drug Designation for Patients With Relapsed, Refractory Multiple Myeloma

The FDA granted an orphan drug designation (ODD) to SAR446523 (Sanofi) for the potential treatment of patients with relapsed or refractory multiple myeloma (R/R MM).¹

Concept of multiple myeloma cell | Image Credit: © LELISAT - stock.adobe.com

MM is the second most common hematologic malignancy, of which there are estimated to be over 36,000 new cases in 2025 in the United States. It is characterized by the overproduction of B lymphocytes, leading to renal failure, anemia, and brittle bones. MM is incurable and marked by increasingly poorer responses to therapies with each successive line of treatment. Thereby, a variety of options for treatment is crucial to adjust to the individual, unique needs of each patient.^1,2

Treatment of MM has improved substantially over the past 2 decades, leading to 5-year survival rates of 60%—a significant increase from the 5-year survival rate of 36.7% in the early 2000s. The development of immunotherapies, such as bispecifics or chimeric antigen receptor (CAR) T-cell therapy, and the identification of biomarkers have completely altered outcomes for patients. These discoveries yielded the production of novel drugs capable of selectively targeting cancerous cells, improving depth and durability of responses, and lowering toxicities.^2-4

CAR T-cell therapy is another advancement in the MM treatment landscape. As of 2025, there are 2 FDA-approved CAR T products: ciltacabtagene autoleucel (cilta-cel, Carvykti; Janssen Biotech, Inc) and idecabtagene vicleucel (ide-cel, Abecma; Bristol Myers Squibb), which target BCMA. Although BCMA is a prominent biomarker in MM, others—such as CD19 and GPRC5D—have come to the surface and led to the development of other agents.^5,6

SAR446523 is an investigational IgG1 monoclonal antibody that binds to GPRC5D, a receptor that occurs in approximately 90% of patients with MM. It features a specially engineered Fc region designed to boost immune cell–mediated killing of targeted cells through enhanced antibody-dependent cellular cytotoxicity.⁷

“The [ODD] is a significant milestone in our ongoing efforts to develop innovative treatments in multiple myeloma,” Alyssa Johnsen, MD, PhD, Global Therapeutic Area Head, Immunology and Oncology Development at Sanofi, said in a press release. “This underscores our commitment to multiple myeloma, a disease for which we have acquired strong expertise with the development of another widely used and approved immunotherapy treatment.”⁷

SAR446523 investigations continue, but the designation marks a significant step forward. Subcutaneous SAR446523 is being evaluated in an ongoing phase 1 study in patients with R/R MM (NCT06630806).^7,8

REFERENCES

1. Key statistics about multiple myeloma. American Cancer Society. February 28, 2025. Accessed July 31, 2025. https://www.cancer.org/cancer/types/multiple-myeloma/about/key-statistics.html

2. Gerlach A. Isa-KRd induction achieves 95% response rate in multiple myeloma. Pharmacy Times. July 8, 2025. Accessed July 31, 2025. https://www.pharmacytimes.com/view/isakrd-induction-achieves-95-response-rate-in-multiple-myeloma

3. Survival rates for multiple myeloma. American Cancer Society. June 27, 2025. Accessed July 31, 2025. https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/survival-rates.html

4. Wexler M. Dramatic gains in survival seen in myeloma since early 2000s: Analysis. Rare Cancer. May 8, 2023. Accessed July 31, 2025. https://rarecancernews.com/news/dramatic-gains-in-survival-seen-in-myeloma-since-early-2000s-analysis/

5. FDA’s recent approval of 2 CAR T-cell therapies a ‘big step toward’ long-term control of myeloma for more patients. Leukemia & Lymphoma Society. April 16, 2024. Accessed July 31, 2025. https://www.lls.org/news/fdas-recent-approval-2-car-t-cell-therapies-big-step-toward-long-term-control-myeloma-more

6. GPRC5D-targeted CAR T-cell therapy shows promise after BCMA treatment failure. Pharmacy times. May 5, 2025. Accessed July 31, 2025. https://www.pharmacytimes.com/view/gprc5d-targeted-car-t-cell-therapy-shows-promise-after-bcma-treatment-failure

7. Press Release: Sanofi’s SAR446523, a GPRC5D monoclonal antibody, earns orphan drug designation in the US for multiple myeloma. Sanofi. July 30, 2025. Accessed July 31, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-07-30-05-00-00-3123737

8. A study to investigate the safety and efficacy of SAR446523 injected subcutaneously in adult participants with relapsed/​refractory myeloma. Updated April 23, 2025. Accessed July 31, 2025. https://clinicaltrials.gov/study/NCT06630806?term=NCT06630806&rank=1