In the specialty biologics sector, few therapeutic franchises represent a larger commercial footprint than Darzalex (daratumumab). Developed by Genmab and commercialized by Johnson & Johnson's Janssen Biotech, this anti-CD38 monoclonal antibody has become the cornerstone therapy for multiple myeloma, spanning from newly diagnosed patients to relapsed or refractory clinical settings.
As a multi-billion-dollar product, Darzalex is a prime target for biosimilar developers. However, the commercial and clinical landscape for daratumumab alternatives is highly dynamic, characterized by a rapid formulation shift from intravenous (IV) infusion to subcutaneous (SC) injection, complex patent portfolios, and unique reimbursement economics under the medical benefit.
For oncology formulary directors, clinical pharmacists, and market access teams, understanding when and how daratumumab biosimilars will enter the market is essential for long-term therapeutic planning. This tracker details the status of the clinical pipeline, compares the subcutaneous and intravenous formulation strategies, maps out patent expiration windows, and explains the billing and launch economics that will govern market entry.
Executive Summary & Scenario Analysis
To align on the market landscape for daratumumab biosimilars, we must address the specific questions facing access managers and oncology clinical coordinators.
Scenario Question
Which biosimilar manufacturers are developing daratumumab (Darzalex) alternatives and when will they launch in the US?
Direct Answer
At least four developers have daratumumab biosimilars in active clinical development: Celltrion (CT-P44, Phase III), Shanghai Henlius/Dr. Reddy's (HLX15, both IV and subcutaneous), BIOCAD (Daratumia, approved in Russia but not Western markets), and Xbrane/JOINN Biologics (Xdarzane). In the United States, commercial biosimilar launch is anticipated starting in 2029, following the expiration of core composition and primary patents in late 2028 or early 2029. Because daratumumab is an oncology biologic administered in clinics or infusion centers and billed under the medical benefit (buy-and-bill), the CMS National Average Drug Acquisition Cost (NADAC) retail database contains exactly zero pricing records. Payer access teams must monitor Average Sales Price (ASP) updates and coordinate medical benefit formulary positioning rather than retail pharmacy discount networks.
Subcutaneous vs. Intravenous: The Strategic Lifecycle Shift
The commercial history of Darzalex is defined by one of the most successful lifecycle management strategies in the biopharmaceutical industry.
- Darzalex IV BLA 761036: Originally approved by the FDA on November 16, 2015, as an intravenous infusion. While highly effective, the IV formulation required lengthy infusion times—often taking 7 hours for the first infusion and 3 to 5 hours for subsequent doses. This presented significant scheduling bottlenecks for clinics and prolonged chair-time for patients.
- Darzalex Faspro SC BLA 761145: To address this limitation, Janssen developed a subcutaneous formulation, approved by the FDA on May 1, 2020. Marketed as Darzalex Faspro, this version co-formulates daratumumab with recombinant human hyaluronidase (rHuPH20, licensed from Halozyme Therapeutics). The enzyme temporarily depolymerizes hyaluronan in the subcutaneous tissue, allowing the subcutaneous injection of a large volume (15 mL containing 1,800 mg of daratumumab) in just 3 to 5 minutes.
For a broader conceptual framework of how subcutaneous conversions are deployed to defend branded biologic franchises, see how subcutaneous lifecycle conversions protect branded biologic franchises within oncology therapeutics.
The COLUMBA Trial: Establishing Clinical Non-Inferiority
The clinical transition from intravenous to subcutaneous daratumumab was validated by the landmark Phase III COLUMBA trial (NCT03277105). This randomized, open-label study compared the efficacy and safety of subcutaneous daratumumab (1,800 mg co-formulated with rHuPH20) against the standard intravenous formulation (weight-based dosing) in patients with relapsed or refractory multiple myeloma.
The trial evaluated two primary endpoints to establish non-inferiority:
- Overall Response Rate (ORR): The subcutaneous arm achieved an ORR of 41.1%, compared to 37.1% in the intravenous arm, successfully demonstrating non-inferiority.
- Maximum Trough Concentration (Ctrough): The geometric mean ratio of Ctrough on day 1 of cycle 3 was 1.079 (90% CI: 0.957–1.217), satisfying the pre-specified non-inferiority margin of 0.80.
Beyond efficacy, the COLUMBA trial highlighted a massive safety advantage for the subcutaneous formulation. The rate of infusion-related reactions (IRRs) was dramatically lower in the subcutaneous group:
- Subcutaneous Infusion-Related Reactions: 12.7%
- Intravenous Infusion-Related Reactions: 34.5%
Additionally, the median administration time was reduced from 7 hours (for the first IV infusion) to just 5 minutes for all subcutaneous injections. This combination of equivalent efficacy, significantly lower IRR rates, and unprecedented administration convenience drove rapid market adoption.
The Conversion Rate and Payer Implications
Janssen's transition strategy was highly effective. By late 2025, the substantial majority of U.S. daratumumab volume had shifted from the IV formulation to the subcutaneous Darzalex Faspro, with the SC product accounting for the bulk of the franchise's reported sales.
[Patient Population]
│
├──► Majority Subcutaneous (Darzalex Faspro - BLA 761145)
│ └── Administered in 3-5 minutes
│ └── Co-formulated with rHuPH20 (Halozyme)
│ └── IRR rate: 12.7%
│
└──► Minority Intravenous (Darzalex IV - BLA 761036)
└── Administered via 3-7 hour infusion
└── IRR rate: 34.5%
For biosimilar developers, this rapid conversion reshaped clinical development requirements. A developer introducing a biosimilar that only matches the IV formulation (BLA 761036) would target a rapidly shrinking clinical niche — the residual minority of the market still on the older infusion product.
To capture significant market share, developers have had to invest in dual clinical development programs or subcutaneous-first formulations, navigating the clinical and regulatory hurdles of matching the co-formulated hyaluronidase delivery system.
The Clinical Pipeline: Leading Daratumumab Biosimilar Candidates
Several global biopharmaceutical companies are advancing daratumumab biosimilars through Phase I and Phase III clinical trials.
1. Celltrion: CT-P44
Celltrion is a prominent developer in the biosimilar space and has targeted the subcutaneous formulation.
- Candidate: CT-P44 (daratumumab subcutaneous biosimilar).
- Clinical Status: In global Phase III clinical development. In September 2025, Celltrion received approval from the European Medicines Agency (EMA) for its Phase III clinical trial plan, following earlier clearances from the U.S. FDA and South Korean regulators.
- Trial Protocol: The Phase III study (ClinicalTrials.gov Identifier: NCT06253481) is a randomized, double-blind, active-controlled trial comparing subcutaneous CT-P44 to reference Darzalex Faspro. The study evaluates the efficacy, safety, pharmacokinetics, and immunogenicity of CT-P44 in combination with lenalidomide and dexamethasone (the DRd regimen) in patients with relapsed or refractory multiple myeloma.
- Pharmacokinetic and Efficacy Endpoints: The primary endpoints include the Overall Response Rate (ORR) and maximum trough concentration (Ctrough) at cycle 3, mimicking the COLUMBA design. The study is powered to show non-inferiority within the standard FDA/EMA-accepted biosimilar margins.
- Timeline: Enrollment is actively ongoing, with an estimated primary completion date projected for November 2027.
2. Shanghai Henlius Biotech & Dr. Reddy's: HLX15
Shanghai Henlius Biotech has pursued a dual-track strategy, developing both intravenous and subcutaneous biosimilar versions of daratumumab.
- Candidate: HLX15 (daratumumab biosimilar).
- Intravenous Pipeline: Henlius is conducting a randomized, double-blind Phase III clinical trial (NCT06895512) comparing the efficacy and safety of HLX15-IV to reference Darzalex IV in combination with lenalidomide and dexamethasone for relapsed or refractory multiple myeloma. The primary objective is to demonstrate therapeutic equivalence in ORR.
- Subcutaneous Pipeline: Recognizing the market transition, Henlius developed a subcutaneous version, HLX15-SC, co-formulated with recombinant human hyaluronidase. An international, multi-center Phase I trial comparing the pharmacokinetics and safety of HLX15-SC to Darzalex Faspro dosed its first patient in May 2026. The pharmacokinetic equivalence is evaluated based on Area Under the Curve (AUC) and maximum serum concentration (Cmax).
- Commercialization Deal: In February 2025, Henlius signed an exclusive licensing agreement with Dr. Reddy's Laboratories. Dr. Reddy's secured commercialization rights for HLX15 (both IV and SC formulations) in the United States, Europe (covering 42 countries), and select emerging markets, with Henlius retaining manufacturing rights.
3. BIOCAD: Daratumia (BCD-180)
BIOCAD, a Russian biotechnology company, has achieved the earliest regulatory approval for a daratumumab biosimilar.
- Candidate: Daratumia (BCD-180).
- Status: In August 2025, the Russian Ministry of Health approved BIOCAD's Daratumia, making it the first approved daratumumab biosimilar globally.
- Market Context: Daratumia is marketed in Russia and select CIS countries. However, because BIOCAD's clinical trial data has not been reviewed or validated by the U.S. FDA or the EMA, Daratumia is not authorized for use in Western markets. It serves as a proof of concept for biosimilar analytical similarity but does not affect U.S. or EU market access timelines.
4. Xbrane Biologics & JOINN Biologics: Xdarzane
- Candidate: Xdarzane.
- Status: Xbrane Biologics and JOINN Biologics have partnered to co-develop a biosimilar candidate. The program is currently in preclinical and early clinical planning stages, targeting both the Western biosimilar pathways and manufacturing efficiencies in China.
Daratumumab Biosimilar Pipeline Summary
The following table summarizes the status and development pathways of the leading daratumumab biosimilar candidates.
| Candidate Name | Developer(s) | Target Formulation | Development Phase | Key Trial Identifiers | Western Licensee | Expected U.S. Launch |
|---|---|---|---|---|---|---|
| CT-P44 | Celltrion | Subcutaneous | Phase III | NCT06253481 | Celltrion USA | ~2029 |
| HLX15-IV | Henlius | Intravenous | Phase III | NCT06895512 | Dr. Reddy's | ~2029 |
| HLX15-SC | Henlius | Subcutaneous | Phase I (FPI May 2026) | Not yet registered | Dr. Reddy's | ~2029–2030 |
| Daratumia | BIOCAD | Intravenous | Approved (Russia) | Local studies | None (CIS only) | N/A (No U.S. path) |
| Xdarzane | Xbrane / JOINN | Intravenous | Preclinical / Ph I | Preclinical | To be decided | Post-2030 |
Patent Expiration & Market Entry Timelines
Determining the exact U.S. market entry window for daratumumab biosimilars requires analyzing the patent estates listed in the FDA Purple Book and Genmab's commercial disclosures.
Biologic patent estates are complex, consisting of composition-of-matter patents, formulation patents, cell line culture patents, and method-of-use patents.
U.S. Patent Expiration Window: 2029
According to Genmab's financial reports and regulatory filings, the U.S. patent protection for daratumumab is projected to expire in 2029.
- Primary Composition Patent: The core composition-of-matter patent for the daratumumab antibody structure is scheduled to expire in late 2028 or early 2029, depending on the application of patent term restorations.
- Formulation Exclusivity & Halozyme ENHANZE Patents: While composition patents expire in 2029, Janssen has built a supplementary patent estate around the subcutaneous formulation (Darzalex Faspro). This includes patents covering the co-formulation ratio with recombinant human hyaluronidase and specific injection devices. Under the licensing agreement with Halozyme, the patents protecting the recombinant human hyaluronidase technology (the ENHANZE platform) are valid through 2027 in the U.S. and 2029 in Europe. Any biosimilar developer targeting the subcutaneous market must navigate both the daratumumab antibody patents and the hyaluronidase technology patents.
Biosimilar developers targeting the subcutaneous market must ensure their formulations do not infringe these active formulation patents or must challenge them through the Patent Trial and Appeal Board (PTAB) or the Unified Patent Court (UPC) in Europe.
European Patent Expiration Window: 2031–2032
In Europe, the patent protection window is extended beyond that of the U.S. due to Supplementary Protection Certificates (SPCs) and pediatric extensions.
- European Patent Expiration: The basic patent for daratumumab in Europe is expected to expire in 2031 or 2032, ensuring a longer branded monopoly for Janssen and Genmab in European markets.
- Royalty Structure: Because Genmab's royalty agreements with Janssen are structured around the "last-to-expire" relevant patent on a country-by-country basis, Genmab will continue to collect royalties on U.S. sales until late 2029, and on European sales well into the 2030s.
Based on clinical trial progress (Celltrion's CT-P44 Phase III finishing in late 2027 and Henlius's HLX15 SC trial progression), the regulatory review timeline (typically 12 months for a 351(k) BLA), and the patent expiration dates, payers should expect the first U.S. daratumumab biosimilar launches in mid-to-late 2029.
Medical-Benefit Billing & ASP Lag: Launch Economics
Because daratumumab is an oncology biologic administered in outpatient clinics, hospital infusion centers, or physician offices, it is reimbursed under the medical benefit rather than the pharmacy benefit. This has significant implications for how payers manage access and how providers adopt biosimilars.
For a detailed analysis of how buy-and-bill reimbursement and average sales price mechanics function during biosimilar launches, see buy-and-bill reimbursement and ASP lag challenges during biosimilar launch.
The Buy-and-Bill System
Healthcare providers purchase Darzalex directly from wholesalers and bill payers after administering the drug to the patient. Payers reimburse providers based on the drug's Average Sales Price (ASP) plus a percentage-based administration fee (typically ASP + 4% or ASP + 6%).
- HCPCS Codes:
- J9145: Injection, daratumumab, 10 mg (refers to Darzalex IV)
- J9144: Injection, daratumumab, 10 mg and hyaluronidase-fihj, 10,000 units (refers to Darzalex Faspro)
The Average Sales Price (ASP) Lag Challenge
When a new biosimilar launches, its initial ASP is not yet established because the manufacturer has not yet reported a quarter's worth of sales data. During the first two quarters of launch, reimbursement is typically anchored to the Wholesale Acquisition Cost (WAC) plus roughly 6% (the standard Part B administration margin).
Once sales data is collected, CMS publishes a specific ASP for the biosimilar (typically using a unique Q-code or J-code). Because ASP is calculated retroactively based on historical sales data, there is a two-quarter lag between when discounts are offered and when the official ASP drops.
This ASP lag creates financial risk for oncology clinics:
- Under-Reimbursement Risk: If a clinic purchases a biosimilar at WAC but the payer's reimbursement rate drops rapidly due to aggressive manufacturer rebates, the clinic's reimbursement may fall below its acquisition cost.
- Provider Hesitancy: Providers are often hesitant to switch patients from reference Darzalex to a newly launched biosimilar until the biosimilar's ASP stabilizes and billing codes are clearly defined, fearing reimbursement delays or financial losses.
Payer Management Strategy for Daratumumab Biosimilars
To drive biosimilar adoption and capture savings in 2029, payers should prepare to implement the following policies:
- Formulary Preference: Payers should design "biosimilar preferred" medical policies, requiring the use of a preferred daratumumab biosimilar before brand Darzalex or Darzalex Faspro is approved, except in cases of documented clinical exception.
- ASP-Based Fee Schedule Adjustments: Payers can mitigate provider hesitancy by guaranteeing stable reimbursement rates during the first two quarters of launch, indexing reimbursement to the brand's ASP to ensure clinics are not financially penalized for choosing the biosimilar.
- Site-of-Care Optimization: Payers should direct patients to lower-cost administration settings (such as independent oncology clinics or home-infusion providers) rather than high-cost hospital outpatient departments, which often add significant facility fees to medical benefit claims.
The Rise of White-Bagging and Brown-Bagging
To control the markup associated with buy-and-bill billing, many payers have turned to alternative specialty distribution channels:
- White-Bagging: The clinic submits a prescription to a specialty pharmacy. The pharmacy dispenses the drug and ships it directly to the clinic, where it is administered. The specialty pharmacy bills the payer directly under the pharmacy benefit, bypassing the clinic's buy-and-bill markup.
- Brown-Bagging: The patient obtains the specialty drug directly from a pharmacy and carries it to the provider's clinic for administration. Because of safety concerns (such as temperature-control failures during transport) and oncologists' resistance, brown-bagging is rarely permitted for complex oncology biologics like daratumumab.
- Oncology Provider Resistance: Oncology practices strongly oppose white-bagging for daratumumab due to inventory logistics, liability risks, and the loss of buy-and-bill revenue. Payers must balance these network-management friction points against the potential cost-savings of shifting oncology biologics to pharmacy benefits.
FAQ Section
Will daratumumab biosimilars be interchangeable with both IV and subcutaneous brand formulations?
No. An interchangeable biosimilar designation requires a product to be biosimilar to the specific reference product and demonstrate that it produces the same clinical result in any given patient. Because Darzalex IV (BLA 761036) and Darzalex Faspro SC (BLA 761145) are licensed under separate BLAs with different routes of administration, a biosimilar developer must seek separate biosimilar licenses for each. A biosimilar licensed as biosimilar to Darzalex IV cannot be substituted for Darzalex Faspro at the pharmacy level.
Why are there no pricing records for daratumumab in retail pharmacy databases like CMS NADAC?
Daratumumab is a medical-benefit biologic administered by healthcare professionals in clinical settings. Because it is not dispensed via retail pharmacies to patients for self-administration, it does not generate retail pharmacy acquisition cost records, resulting in zero entries in retail pricing databases like CMS NADAC. Payers must reference CMS ASP pricing files instead.
What is the role of recombinant human hyaluronidase (rHuPH20) in the subcutaneous formulation?
Recombinant human hyaluronidase (rHuPH20) is an enzyme that temporarily breaks down hyaluronic acid in the extracellular matrix of subcutaneous tissue. This increases tissue permeability, allowing the rapid injection of a large volume of liquid (such as the 15 mL Darzalex Faspro dose) without causing severe local tissue tension or pain. The subcutaneous tissue returns to its normal state within 24 to 48 hours.
Which developers are leading the subcutaneous daratumumab biosimilar pipeline?
Celltrion (with CT-P44) and Shanghai Henlius Biotech (with HLX15-SC, licensed to Dr. Reddy's) are the leading developers with subcutaneous candidates in active clinical trials. Celltrion's candidate is in Phase III development, while Henlius initiated Phase I subcutaneous trials in May 2026.
How does the FDA define a biosimilar versus an interchangeable biologic?
A biosimilar is a biologic that is highly similar to an FDA-approved reference product, with no clinically meaningful differences in safety, purity, and potency. An interchangeable biologic is a biosimilar that meets additional clinical standards, proving that it can be substituted for the reference product at the pharmacy counter without the intervention of the prescribing healthcare provider, similar to generic small-molecule drugs.
What is the primary difference in patient administration between the IV and SC formulations of daratumumab?
The primary difference is administration time and safety. The intravenous formulation (Darzalex IV) requires a slow intravenous infusion lasting between 3 to 7 hours, depending on patient tolerance and the occurrence of infusion reactions. The subcutaneous formulation (Darzalex Faspro) is administered via a single subcutaneous injection into the abdomen over approximately 3 to 5 minutes, with a significantly lower rate of infusion-related reactions.
Sources
- FDA Purple Book: Database of Licensed Biological Products, BLAs 761036 and 761145. U.S. Food and Drug Administration. Accessed June 2026. https://purplebooksearch.fda.gov
- Celltrion Inc. "A Phase 3, Randomized, Double-Blind, Active-Controlled Study to Compare the Efficacy and Safety of CT-P44 Subcutaneous with Reference Darzlex Faspro in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma." ClinicalTrials.gov Identifier: NCT06253481. National Institutes of Health. https://clinicaltrials.gov/study/NCT06253481
- Shanghai Henlius Biotech, Inc. "A Phase 3 Study to Compare HLX15 with Reference Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma." ClinicalTrials.gov Identifier: NCT06895512. National Institutes of Health. https://clinicaltrials.gov/study/NCT06895512
- Shanghai Henlius Biotech, Inc. Press Release: "Henlius Enters into Licensing Agreement with Dr. Reddy's for Daratumumab Biosimilar HLX15 in the US and Europe." Commercial disclosures published February 2025. https://www.henlius.com/en/NewsDetails-5752-26.html
- Genmab A/S. Annual Report 2025 (Form 20-F). Filed with the U.S. Securities and Exchange Commission on February 18, 2026. Royalty and Patent Expiration disclosures. https://www.sec.gov/ix?doc=/Archives/edgar/data/0001431327/000143132726000010/genmab-20251231.htm
- Centers for Medicare & Medicaid Services (CMS). Medicare Part B Drug Average Sales Price (ASP) Files, Q2 2026 release. Medical Benefit Reimbursement Rates. https://www.cms.gov/medicare/payment/fee-for-service-providers/part-b-drugs/average-sales-price
- Pearce IP Law News. "EMA Approves Phase 3 Trial for Celltrion's Daratumumab Biosimilar CT-P44." Biologics Intellectual Property reports. Published September 2025. https://www.pearceip.law/2025/09/01/eu-approves-ph-3-trial-for-celltrions-daratumumab-biosimilar/
- Mateos, M. V., et al. "Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial." The Lancet Oncology, 2020. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30081-4/fulltext
