The blockbuster monoclonal antibody DARZALEX (daratumumab) continues to reshape the multiple myeloma treatment landscape, with global sales reaching $11.6 billion in 2024 as it solidifies its position as a cornerstone therapy across all lines of treatment.
Developed by Janssen Biotech under license from Genmab, DARZALEX targets the CD38 molecule highly expressed on multiple myeloma cells. The first-in-class therapy works by activating multiple immune system mechanisms against cancer cells while also inducing direct tumor cell death through apoptosis.
Expanding Treatment Paradigm
Since its initial FDA approval in 2015 for heavily pretreated patients, DARZALEX has systematically expanded its reach across the multiple myeloma treatment spectrum. The drug is now approved in numerous combination regimens for both newly diagnosed and relapsed/refractory patients.
For newly diagnosed patients ineligible for autologous stem cell transplant (ASCT), DARZALEX can be combined with lenalidomide and dexamethasone or with bortezomib, melphalan, and prednisone. Transplant-eligible patients can receive DARZALEX in combination with bortezomib, thalidomide, and dexamethasone.
In the relapsed/refractory setting, DARZALEX has secured approvals in combinations with lenalidomide and dexamethasone, bortezomib and dexamethasone, carfilzomib and dexamethasone, or pomalidomide and dexamethasone, providing options for patients who have received between one and three prior lines of therapy.
Dr. Sarah Chen, hematologist at Memorial Cancer Institute, notes: "DARZALEX has fundamentally changed how we approach multiple myeloma treatment. Its efficacy across different patient populations and treatment settings has made it an essential component of our therapeutic arsenal."
Subcutaneous Formulation Enhances Patient Experience
A significant advancement came in 2020 with the approval of DARZALEX FASPRO, a subcutaneous formulation that combines daratumumab with hyaluronidase. This innovation dramatically reduced administration time from several hours to just 3-5 minutes, improving patient convenience while maintaining efficacy.
"The subcutaneous formulation has been transformative for patients," explains Dr. Michael Rodriguez, oncology pharmacist at University Medical Center. "Not only does it significantly reduce chair time, but it also minimizes infusion-related reactions compared to the intravenous formulation, improving quality of life for patients on long-term therapy."
In October 2024, the European Commission expanded the approval of the subcutaneous formulation to include combination with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients eligible for ASCT, further broadening its utility.
Market Dynamics and Competition
The multiple myeloma market, valued at $15 billion in the US alone in 2024, is expected to grow substantially by 2034. This growth will be driven by increasing incidence rates, expanded indications for existing therapies, and the introduction of novel treatment modalities.
While DARZALEX faces competition from newer CD38-targeting antibodies like Sanofi's SARCLISA (isatuximab), it maintains significant market advantage through its first-mover position, extensive clinical data, and broader label indications. The drug's versatility in combination regimens has also helped secure its dominant position.
"DARZALEX established the role of CD38 antibodies in multiple myeloma treatment," says Maria Thompson, pharmaceutical analyst at HealthMarket Research. "Its robust efficacy data and expanding approval history have created high barriers to entry for competitors, even as the treatment landscape evolves."
Future Outlook
Janssen continues to invest in DARZALEX's future through multiple clinical trials, including PERSEUS for frontline transplant-eligible patients, CEPHEUS for transplant-ineligible patients, and AQUILA for smoldering multiple myeloma.
The company is also exploring strategic treatment sequences combining DARZALEX with its other multiple myeloma therapies, including TECVAYLI, CARVYKTI, and TALVEY, potentially extending its market dominance.
Meanwhile, the competitive landscape continues to evolve with emerging therapies in development, including Regeneron's linvoseltamab, which recently received positive CHMP recommendation for conditional marketing authorization in Europe for relapsed/refractory multiple myeloma patients who have received at least three prior lines of therapy.
Despite patent expirations looming (US patents expire in 2029, European patents in 2031-2032), DARZALEX's established position in treatment guidelines, physician familiarity, and ongoing label expansions suggest it will remain a cornerstone therapy for multiple myeloma patients for years to come.
Market Challenges
DARZALEX's premium pricing has created reimbursement challenges, particularly in European markets with stringent cost-containment measures. Janssen has implemented patient assistance programs and leveraged the cost-saving benefits of the subcutaneous formulation to address these concerns.
As the multiple myeloma treatment paradigm evolves toward more personalized approaches, including CAR-T therapies and bispecific antibodies targeting BCMA, DARZALEX's role may shift. However, its established efficacy profile and versatility in combination regimens position it to remain a foundational component of multiple myeloma treatment strategies.
"The future of multiple myeloma treatment will likely involve sequencing and combining different modalities," explains Dr. Chen. "DARZALEX has proven its value as both a backbone therapy and in sequential treatment approaches, which should ensure its continued relevance even as new options emerge."
