Executive Summary

CD38 has matured from a niche myeloma target into a major plasma-cell biology platform. In 2026, the commercial center remains multiple myeloma, led by daratumumab and followed by isatuximab, while the next strategic frontier is split between formulation competition, front-line regimen expansion, biosimilar entry planning, and attempts to translate CD38-mediated plasma-cell depletion into autoimmune and renal diseases.

The practical landscape is no longer a simple two-product oncology comparison. Daratumumab has the dominant commercial base, extensive front-line use, a subcutaneous formulation, and a newly approved high-risk smoldering multiple myeloma indication. Isatuximab is smaller but increasingly relevant in front-line transplant-ineligible disease, EU transplant-eligible disease, and subcutaneous on-body injector development.

The most important readout for industry strategy is not only efficacy. It is convenience, durability of exclusivity, geographic expansion, and whether newer anti-CD38 programs can move beyond malignant plasma cells into pathogenic antibody-driven disease without reproducing the same treatment burden.

Why CD38 Matters

CD38 is a cell-surface glycoprotein expressed at high levels on malignant plasma cells in multiple myeloma and on antibody-producing plasma-cell lineage cells more broadly. Approved CD38-directed antibodies use this biology to target plasma cells through immune-mediated mechanisms, making CD38 both an established myeloma target and an emerging target for diseases where pathogenic antibody-producing cells are implicated. 1234

In oncology, the approved CD38 products are monoclonal antibodies that bind CD38 on myeloma cells and are used in combination regimens across relapsed, refractory, and newly diagnosed multiple myeloma settings. Outside oncology, investigational CD38 antibodies such as mezagitamab and felzartamab are being developed around a related but distinct therapeutic hypothesis: depleting CD38-expressing plasma cells or related immune-cell populations that may drive antibody-mediated disease. 56734

Market Structure in 2026

The U.S. CD38 product market is anchored by two approved antibody active substances: daratumumab, marketed as DARZALEX and DARZALEX FASPRO by Johnson & Johnson, and isatuximab-irfc, marketed as SARCLISA by Sanofi. DARZALEX was approved in 2015 for heavily pretreated multiple myeloma and was described by Johnson & Johnson as the first human anti-CD38 monoclonal antibody approved anywhere in the world. SARCLISA entered the U.S. market in 2020 as an anti-CD38 antibody used with pomalidomide and dexamethasone in relapsed refractory multiple myeloma after at least two prior therapies including lenalidomide and a proteasome inhibitor. 12

By 2026, the approved use pattern has shifted materially toward earlier myeloma treatment. DARZALEX FASPRO has FDA approvals that include transplant-eligible newly diagnosed multiple myeloma with VRd induction and consolidation, high-risk smoldering multiple myeloma as monotherapy, and transplant-ineligible newly diagnosed multiple myeloma with VRd. SARCLISA has U.S. approvals that include pomalidomide and dexamethasone after at least two prior therapies, carfilzomib and dexamethasone after one to three prior lines, and VRd for transplant-ineligible newly diagnosed multiple myeloma. 586297

Front-Line Competition

The clearest competitive battleground is now front-line multiple myeloma, especially anti-CD38 plus VRd. FDA approved SARCLISA with VRd for transplant-ineligible newly diagnosed multiple myeloma on September 20, 2024, based on IMROZ, an open-label randomized phase 3 trial of 446 patients. The FDA summary reported a PFS hazard ratio of 0.60, a 40% reduction in risk of progression or death, with median PFS not reached in the Isa-VRd arm and 54.3 months in the VRd arm. 7

FDA approved DARZALEX FASPRO with VRd for transplant-eligible newly diagnosed multiple myeloma on July 30, 2024, based on PERSEUS, which randomized 709 patients and showed a PFS hazard ratio of 0.40, corresponding to a 60% reduction in risk of disease progression or death versus VRd alone. FDA then approved DARZALEX FASPRO with VRd for transplant-ineligible newly diagnosed multiple myeloma on January 27, 2026, based on CEPHEUS, where MRD negativity was 52.3% for DARZALEX FASPRO-VRd and 34.8% for VRd, and the PFS hazard ratio was 0.60. 56

The sourced materials do not establish a direct head-to-head comparison between daratumumab-VRd and isatuximab-VRd in the same trial population. The defensible comparison is therefore regulatory and strategic, not cross-trial superiority: both anti-CD38 antibodies have moved into front-line quadruplet therapy, but the specific trial populations, endpoints, regional approvals, and delivery formats differ. 75610

Administration and Delivery

Formulation has become a core competitive dimension. DARZALEX FASPRO was approved in the United States in 2020 as a fixed-dose subcutaneous formulation of daratumumab and hyaluronidase-fihj, and Genmab reported that the formulation reduced treatment time from hours to minutes while demonstrating similar efficacy and safety with fewer infusion-related reactions compared with intravenous daratumumab in the supporting studies. FDA materials for the high-risk smoldering multiple myeloma approval describe the recommended dose as 1,800 mg daratumumab and 30,000 units hyaluronidase administered subcutaneously over approximately 3 to 5 minutes. 118

Sanofi is pursuing a subcutaneous SARCLISA strategy through an on-body injector. In June 2025, Sanofi stated that two clinical studies supported subcutaneous administration by investigational on-body injector in relapsed or refractory multiple myeloma, including IRAKLIA phase 3 data demonstrating non-inferior efficacy and pharmacokinetics compared with intravenous infusion. In April 2026, Sanofi said FDA extended the target action date for the U.S. BLA for SARCLISA subcutaneous in approved standard-of-care combinations to July 23, 2026, and that CHMP had adopted a positive opinion for SARCLISA SC via on-body injector and manual injection across approved EU indications and combinations for the IV formulation. 1213

The strategic implication is straightforward: once anti-CD38 antibodies become part of long-duration regimens, administration time and site workflow can influence product selection even when efficacy evidence is evaluated within separate clinical programs. This is especially relevant because DARZALEX FASPRO already has an approved subcutaneous U.S. formulation, while SARCLISA SC remained under regulatory review in the sourced U.S. materials as of April 2026. 1113

Commercial Scale and Growth Pattern

DARZALEX remains the commercial outlier in the CD38 class. Genmab reported that worldwide net trade sales of DARZALEX, including intravenous and subcutaneous products reported by Johnson & Johnson, were USD 14,351 million in 2025, with USD 8,266 million in the United States and USD 6,085 million in the rest of the world. Genmab also reported that 2025 DARZALEX sales increased by USD 2,681 million, or 23%, compared with USD 11,670 million in 2024, and that Genmab expected 2026 DARZALEX net sales of USD 15.6 to 16.4 billion in its 2026 outlook. 1415

The 2026 run rate was still expanding in the most recent sourced quarter. Genmab reported first-quarter 2026 DARZALEX net trade sales of USD 3,964 million, including USD 2,208 million in the United States and USD 1,756 million in the rest of the world, compared with USD 3,237 million in the first quarter of 2025 in a later first-quarter financial update. 16

SARCLISA is commercially smaller but growing. Sanofi reported SARCLISA sales of €471 million in 2024, up 29.7% at constant exchange rates, and €588 million in 2025, up 28.5% at constant exchange rates. In first-quarter 2026, Sanofi reported SARCLISA sales of €167 million, up 30.1% at constant exchange rates, supported by high growth in Europe and Rest of World and increased use in earlier treatment lines including front-line transplant-ineligible patients. 171819

The commercial pattern is therefore asymmetric: DARZALEX is already a multi-billion-dollar annual franchise with a U.S.-weighted sales base, while SARCLISA remains a sub-billion-euro product growing from a materially smaller base. The available data support a market story of dominant originator scale plus a faster-moving challenger that is trying to close the clinical and convenience gap through front-line indications and subcutaneous development. 14151617181913

Biosimilar and IP Pressure

Daratumumab exclusivity and biosimilar planning are now part of the CD38 landscape. Johnson & Johnson disclosed in its 2025 Form 10-K that sales of DARZALEX and DARZALEX FASPRO collectively accounted for approximately 15.0% of company revenues in fiscal 2025, that Genmab owns two patent families related to DARZALEX licensed exclusively to Janssen Biotech, and that those two patent families expire in the United States in 2029, with compound and use patent protection in select European countries extending to 2031 or 2032. Johnson & Johnson also stated that Janssen Biotech owns separate patent portfolios related to DARZALEX FASPRO and DARZALEX IV. 20

Henlius and Dr. Reddy's are positioning HLX15 as an investigational daratumumab biosimilar candidate for both the intravenous and subcutaneous daratumumab franchises. Henlius stated in 2025 that HLX15 is a fully human anti-CD38 IgG1κ monoclonal antibody being developed as a biosimilar candidate to DARZALEX and DARZALEX FASPRO, and that Dr. Reddy's received exclusive rights to commercialize both IV and SC formulations in the United States and 42 European countries and regions. 21

In February 2026, Henlius announced U.S. FDA clearance of an IND for a Phase 1 study of HLX15-SC, the subcutaneous formulation of HLX15, intended for first-line treatment of multiple myeloma. Henlius also stated that its IV Phase 1 clinical study had been completed in June 2024 and met its primary endpoint, while HLX15 and reference daratumumab were considered comparable based on analytical similarity and preclinical studies. 22

Pipeline Beyond Oncology

The next layer of CD38 development is not simply another myeloma antibody. It is the attempt to use CD38 as a plasma-cell depletion target in diseases driven by pathogenic antibodies, especially renal and immune-mediated conditions. Takeda describes mezagitamab as a fully human anti-CD38 IgG1 monoclonal antibody that depletes high CD38 expressors such as plasma cells, plasmablasts, and natural killer cells, and states that the molecule was in Phase 3 clinical development for both primary IgA nephropathy and chronic immune thrombocytopenia in 2025. Takeda also stated that mezagitamab had EMA orphan designation for primary IgA nephropathy and FDA breakthrough therapy designation for adult chronic immune thrombocytopenia after insufficient response to previous treatment. 3

Biogen similarly frames felzartamab as an investigational human monoclonal antibody directed against CD38 on mature plasma cells. Biogen stated in June 2025 that felzartamab had three Phase 3 programs in rare kidney diseases, and that the candidate had not been approved by any regulatory authority and its safety and effectiveness had not been established. 4

This pipeline direction changes the relevance of CD38 beyond oncology. If validated, the class could become a broader pathogenic plasma-cell depletion platform, but the sourced materials still support that conclusion only as a development hypothesis, not as an approved non-oncology product category. 34

Strategic Implications

For product strategy, the most important CD38 questions in 2026 are less about whether the target works in myeloma and more about how much clinical, operational, and economic differentiation remains possible. DARZALEX FASPRO has the strongest evidence of market adoption in the sourced commercial data, with worldwide 2025 net trade sales above USD 14 billion and first-quarter 2026 net trade sales approaching USD 4 billion. SARCLISA has meaningful growth but remains far smaller, making its front-line expansion and SC on-body injector regulatory pathway central to its competitive narrative. 1416181913

For regulatory and evidence strategy, the front-line anti-CD38 field now depends on trial-specific positioning. PERSEUS, CEPHEUS, IMROZ, AQUILA, IKEMA, ICARIA-MM, and GMMG-HD7 each support distinct clinical or regional claims in the sourced materials, but the materials do not support a simple same-population efficacy ranking across products. The more defensible frame is that CD38 antibodies are being embedded progressively earlier in the myeloma treatment sequence, with product differentiation shifting toward formulation, regimen breadth, patient segment, and commercial access. 56879210

For business development, the class now has three investable layers: the incumbent DARZALEX franchise and its post-2029 patent context, the SARCLISA challenger path across front-line and subcutaneous delivery, and a non-oncology pipeline that is testing whether CD38 plasma-cell depletion can become a renal and immune-mediated disease platform. Each layer has a different risk profile: commercial durability, formulation conversion, biosimilar feasibility, or clinical translation outside cancer. 20132234

Unspecified and Watch Items

Several details remain unspecified in the sourced materials. They do not provide a complete worldwide CD38 sales dataset from 2010 through 2026 for every region and formulation, nor do they provide a validated same-currency comparison between DARZALEX and SARCLISA across all years. Reported sales are also not directly comparable without adjustment because DARZALEX figures cited here are reported in U.S. dollars by Genmab based on Johnson & Johnson net trade sales, while SARCLISA figures are reported in euros by Sanofi. 1416171819

The sourced materials also do not establish approved non-oncology CD38 products. Mezagitamab and felzartamab are described as investigational, and HLX15 is described as a daratumumab biosimilar candidate. Accordingly, non-oncology CD38 use and biosimilar entry should be treated as pipeline and market-formation questions rather than approved-product conclusions. 342122