Breakthrough Clinical Results
Sanofi announced that the FDA granted orphan drug designation to SAR446523, a monoclonal antibody targeting GPRC5D, for the treatment of relapsed or refractory multiple myeloma (R/R MM). This designation is given to therapies addressing rare diseases affecting fewer than 200,000 people in the US. SAR446523 is an IgG1-based antibody designed to enhance antibody-dependent cell-mediated cytotoxicity. The drug is currently in a Phase 1, first-in-human study in patients with R/R MM. Multiple myeloma is a rare but significant hematologic malignancy, and new treatment options are needed, especially for patients ineligible for transplants.
Key Highlights
- FDA grants orphan drug designation to Sanofi's SAR446523 for multiple myeloma.
- SAR446523 is a GPRC5D-targeting monoclonal antibody designed to enhance antibody-dependent cell-mediated cytotoxicity.
- The drug is currently in a Phase 1, first-in-human clinical trial (NCT06630806).
- Multiple myeloma is a rare but significant cancer with a high unmet need for new treatments.
Incidence and Prevalence
Global Incidence and Prevalence of Multiple Myeloma
Multiple myeloma (MM) represents approximately 1% of all cancer worldwide and is the second most common hematologic malignancy worldwide. It accounts for almost 15% of all neoplastic malignancies around the globe.
Global Incidence
The annual worldwide incidence of multiple myeloma is estimated to be 6-7/100,000 inhabitants, though some earlier studies reported slightly lower rates of 4-6/100,000. The incidence increases markedly with age across all populations studied.
Regional Variations
Significant geographical and racial disparities exist in multiple myeloma epidemiology:
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In Germany, there are about 6,000 cases of newly diagnosed multiple myeloma per annum.
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In Golestan province (northern Iran), the age-standardized incidence rates (ASRs) of multiple myeloma were 2.66 and 1.97 per 100,000 in males and females, respectively. This region shows geographical diversities in incidence, with high incidence areas in the central and western regions.
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In Taiwan, a study identified 7,285 patients with newly diagnosed multiple myeloma between 1997 and 2013, with an average incidence of 1.83 per 100,000 people and mortality accounting for 0.44 per 100,000 deaths.
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Among Latin American countries, Brazil had the highest incidence, 5-year prevalence, and mortality, while Uruguay had the lowest rates in these categories.
Racial and Ethnic Disparities
Racial disparities in multiple myeloma are particularly notable:
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The incidence is at least two times higher in Blacks/African Americans compared with their White counterparts.
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Some studies report that multiple myeloma is two- to three-fold more common in African Americans compared to European Americans, representing one of the highest disparities of any cancer.
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Hispanics/Latinxs are among the youngest patients diagnosed with the disease.
Age and Gender Distribution
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In Taiwan, the mean age of MM patients was 68.71 years with 85.11% of patients being >55 years of age. The proportion of male patients was greater than female (59.90% vs. 40.10%).
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In Latin American countries, participants' median age ranged from 54 to 67 years.
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A study from Pakistan identified 403 Multiple Myeloma patients with a median age at presentation of 55 years.
Disease Characteristics
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Immunoglobulin G was identified as the most common subtype in Latin American countries.
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Stage III MM was frequently diagnosed in Latin American countries.
Treatment Disparities
Recent advances in available treatments for MM have demonstrated significant improvement in survival outcomes; however, patients from non-White racial/ethnic groups clinically benefit less due to multiple factors including access to care, socioeconomic status, medical mistrust, underutilization of novel therapies, and exclusion from clinical trials.
Economic Burden
Economic Burden of Multiple Myeloma Treatment in USA and Europe
United States Economic Burden
Recent studies reveal the substantial economic impact of multiple myeloma (MM) treatment in the United States. A 2019 study found that average total all-cause costs per-patient per-month (PPPM) were $22,527 in first-line treatment, increasing to $35,266 in second-line and $47,417 in third-line treatment. Anti-MM pharmacy costs represented 22%, 29% and 29% of these totals, respectively.
A more recent 2024 study examining temporal changes showed a 35% decrease in risk for death among patients diagnosed in 2011-2014 compared to 2006-2010. However, this improvement came with 18% and 26% increases in all-cause and multiple myeloma-specific healthcare costs. Adjusted mean all-cause costs increased from $13,960 to $16,449, while adjusted mean multiple myeloma-specific costs rose from $7,476 to $9,422.
For specific treatment regimens, triplet regimens in previously treated MM had estimated costs per patient ranging from $13,890 (DARA/BOR/DEX) to $27,432 (CAR/LEN/DEX) as of 2019. A 2021 study found that first-line daratumumab treatment resulted in lifetime expenditures of $1,434,937 compared to $1,112,101 when reserved for second-line treatment.
European Economic Burden
The economic burden varies significantly across European countries:
In Portugal (2021), the average yearly direct costs per patient amounted to €31,449, with total direct costs estimated at €61 million per year.
Italy (2014) reported a total cost of illness of €19,267.1 ± 25,078.6 per patient, with significant variation by disease stage: from €959.3 for asymptomatic patients to €59,243.7 for those receiving autologous stem-cell transplantation.
Finland (2024) reported mean all-cause healthcare costs of €46,000 per patient-year, with patients averaging 96 healthcare contacts annually.
In the Netherlands (2023), patients received up to 16 lines of therapy with average lifetime costs of €209,871 (€3,111/month) for anti-MM drugs. Notably, 85% of patients received anti-MM treatment in the last 3 months before death, incurring costs of €20,761 (10% of total).
A Danish study (2022) found total observed costs for 41 patients was €8.84 million during 125 treatment years, with a mean 3-year cost per patient of €182,103 from first progression.
In Belgium (2024), oncological home hospitalization models showed higher costs than standard care, with insufficient reimbursement from National Health Insurance.
Common Cost Drivers
Across both regions, the main cost drivers were consistently drugs/medications and hospital admissions. Autologous stem-cell transplantation (ASCT) represented a significant cost component in multiple studies. Novel agents (including bortezomib, lenalidomide, and other immunomodulators) were major contributors to medication costs.
Healthcare resource utilization was typically highest during the first year after diagnosis and during the last year of patients' lives. The studies consistently show that while survival has improved, this has been accompanied by substantial increases in treatment costs.
Drug used in other indications
Clinical Indications for SAR446523 Beyond Multiple Myeloma
Based on a comprehensive review of the available information, isatuximab (SAR446523) does not appear to be currently evaluated in clinical trials for any indications other than multiple myeloma.
The clinical development of isatuximab has been exclusively focused on multiple myeloma treatment, particularly for relapsed/refractory multiple myeloma (RRMM). The drug has been studied in various treatment combinations within this single therapeutic area:
- With pomalidomide and dexamethasone (IsaPomDex)
- With dexamethasone alone (Isa-dex)
- With carfilzomib and dexamethasone
- With dexamethasone and methylprednisolone (ISAdm)
No alternative disease states or additional clinical indications have been identified in the current clinical trial landscape for this investigational agent.
Since there are no trials for indications beyond multiple myeloma, there are no corresponding intervention models to report for other conditions.
The therapeutic focus of isatuximab remains centered on addressing the unmet needs in multiple myeloma treatment, where it continues to be evaluated in various combination regimens to optimize efficacy and safety profiles for patients with this hematological malignancy.