DARZALEX® (daratumumab) receives the first positive CHMP opinion for patients with high-risk smouldering multiple myeloma

BEERSE, BELGIUM (20 June 2025) – Janssen-Cilag International NV, a Johnson & Johnson company, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of a new indication for DARZALEX^® (daratumumab) subcutaneous (SC) formulation as monotherapy for the treatment of adult patients with smouldering multiple myeloma (SMM) at high-risk of developing multiple myeloma.³ If approved, daratumumab could shift the treatment paradigm by becoming the first approved therapy for this disease.¹

SMM is an asymptomatic intermediate disease state of multiple myeloma where abnormal cells can be detected in the bone marrow.¹ The current standard of care (SOC) for SMM, even in high-risk cases, is active monitoring (or “Watch and Wait”) to track for signs of biochemical progression and/or end-organ damage.¹ This means therapeutic intervention is only offered when the disease progresses.¹

“The positive recommendation from the CHMP marks an important step towards addressing the needs of people living with high-risk smouldering multiple myeloma,” said Ester in’t Groen, EMEA Therapeutic Area Head Haematology, Johnson & Johnson Innovative Medicine. “Early disease intervention with daratumumab has the potential to reduce the risk of progression to active multiple myeloma or death by 51 percent for patients with high-risk disease. Pending European Commission approval, patients and physicians will have an option to treat high-risk smouldering multiple myeloma, with the aim to intercept this complex blood cancer before it develops into active disease and importantly, before end-organ damage occurs.”

The CHMP recommendation is supported by data from the Phase 3 AQUILA study ( NCT03301220 ), evaluating the efficacy and safety of fixed-duration monotherapy daratumumab SC compared with active monitoring in those with high-risk SMM.² Johnson & Johnson also submitted a supplemental Biologics License Application to the U.S. Food and Drug Administration seeking approval of a new indication for daratumumab SC for the treatment of adult patients with high-risk SMM, based on the Phase 3 AQUILA data, on 8th November 2024. The first data from the study were previously presented at the 2024 American Society of Hematology (ASH) Annual Meeting and simultaneously published in the New England Journal of Medicine.^2,4 Daratumumab is currently approved in nine indications for multiple myeloma, five of which are in the frontline setting.⁵

“Daratumumab has become a foundational treatment across all stages of multiple myeloma, and we are on a mission to continue to evolve the treatment paradigm to reach those with high-risk smouldering multiple myeloma who may benefit from proactive earlier intervention,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. “Today’s positive CHMP opinion marks positive scientific progress towards this goal and reinforces our vision of eliminating multiple myeloma.”

About the AQUILA Study
AQUILA ( NCT03301220 ) is a randomised, multicentre Phase 3 study investigating daratumumab SC vs active monitoring in patients (n=390) with high-risk smouldering multiple myeloma (SMM).³ The primary endpoint is progression-free survival and secondary endpoints include time to progression, overall response rate and overall survival.³ Patients in the study were diagnosed with SMM in the last five years and were excluded if they had prior exposure to approved or investigational treatments for SMM or multiple myeloma.³

About Smouldering Multiple Myeloma
SMM is an asymptomatic intermediate disease state of multiple myeloma where abnormal cells can be detected in the bone marrow.^1,6 People living with SMM tend not to show signs or symptoms typically associated with active myeloma, such as bone pain, bone fractures, kidney problems, or anaemia, however as abnormal plasma cells are present, organ damage may begin and progress asymptomatically.^4,7 Approximately fifteen percent of all cases of newly diagnosed multiple myeloma are classified as SMM, and half of those diagnosed with high-risk SMM are estimated to progress to active multiple myeloma within two years.⁸

About Multiple Myeloma
Multiple myeloma is currently an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.^9,10 In multiple myeloma, these malignant plasma cells continue to proliferate, accumulating in the body and crowding out normal blood cells, as well as often causing bone destruction and other serious complications.^9,10 In the European Union, it is estimated that more than 35,000 people were diagnosed with multiple myeloma in 2022, and more than 22,700 patients died.¹¹ Patients living with multiple myeloma experience relapses which become more frequent with each line of therapy^12,13,14 Whilst some patients with multiple myeloma initially have no symptoms, others can have common signs and symptoms of the disease, which can include bone fracture or pain, low red blood cell counts, fatigue, high calcium levels, infections, or kidney damage.¹⁵

About Daratumumab and Daratumumab SC
Johnson & Johnson is committed to exploring the potential of daratumumab for patients with multiple myeloma across the spectrum of the disease.

In August 2012 , Janssen Biotech, Inc., a Johnson & Johnson company, and Genmab A/S entered a worldwide agreement, which granted Johnson & Johnson an exclusive licence to develop, manufacture and commercialise daratumumab. Since launch, daratumumab has become a foundational therapy in the treatment of multiple myeloma, having been used in the treatment of more than 618,000 patients worldwide.¹⁶ Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma.¹⁷ Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE^® drug delivery technology.¹⁷

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.¹⁷ Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death.¹⁷ Daratumumab may also have an effect on normal cells.¹⁷ Data across ten Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.^{18,19,20,21,22,23,24,25,26}

For further information on daratumumab, please see the Summary of Product Characteristics at: https://ec.europa.eu/health/documents/community-register/html/h1101.htm .

About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow. and profoundly impact health for humanity.

Learn more at www.innovativemedicine.jnj.com/emea . Follow us at www.linkedin.com/company/jnj-innovative-medicine-emea . Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc. and Janssen Research & Development, LLC are Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of daratumumab. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialise, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behaviour and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s most recent Annual Report on Form 10-K, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at http://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

¹ Myeloma UK. Smouldering Myeloma. Available at: https://www.myeloma.org.uk/library/smouldering-myeloma-infosheet/ . Last accessed: June 2025.

² Dimopoulos MA, et al. Phase 3 Randomized Study of Daratumumab Monotherapy versus Active Monitoring in Patients with High-risk Smoldering Multiple Myeloma: Primary Results of the AQUILA study. Oral presentation. American Society of Hematology (ASH) Annual Meeting; December 7-10, 2024.

³ ClinicalTrials.Gov. A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma. Available at: https://clinicaltrials.gov/study/NCT03301220 . Last accessed: June 2025.

⁴ Dimopoulos MA et al. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. The New England Journal of Medicine 2024. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2409029 . Last Accessed: June 2025.

⁵ European Medicines Agency. Darzalex Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf . Last accessed: June 2025.

⁶ WebMD. Smoldering Multiple Myeloma. Available at: https://www.webmd.com/cancer/multiple-myeloma/smoldering-multiple-myeloma . Last accessed: June 2025.

⁷ American Cancer Society. About Multiple Myeloma. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/about/what-is-multiple-myeloma.html . Last accessed: June 2025.

⁸ Rajkumar SV, et al. Smoldering Multiple Myeloma Current Treatment Algorithms. Blood Cancer J. 2022; 12(9):129.

⁹ Abdi J, et al. Drug Resistance in Multiple Myeloma: Latest Findings on Molecular Mechanisms. Oncotarget. 2013; 4(12):2186-2207.

¹⁰ American Society of Clinical Oncology. Multiple Myeloma: Introduction. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/if-you-have-multiple-myeloma . Last accessed: June 2025.

¹¹ ECIS - European Cancer Information System. Estimates of Cancer Incidence and Mortality in 2022, by Country. Multiple Myeloma. Available at: https://ecis.jrc.ec.europa.eu/explorer.php?$0-0$1-All$2-All$4-1,2$3-51$6-0,85$5-2022,2022$7-7$CEstByCountry$X0_8-3$X0_19-AE27$X0_20-No$CEstBySexByCountry$X1_8-3$X1_19-AE27$X1_-1-1$CEstByIndiByCountry$X2_8-3$X2_19-AE27$X2_20-No$CEstRelative$X3_8-3$X3_9-AE27$X3_19-AE27$CEstByCountryTable$X4_19-AE27 . Last accessed: June 2025.

¹² Bhatt P, Kloock C, Comenzo R. Relapsed/refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse. Curr Oncol. 2023; 30(2):2322-2347.

¹³ Hernández-Rivas JÁ, et al. The Changing Landscape of Relapsed and/or Refractory Multiple Myeloma (MM): fundamentals and controversies. Biomark Res. 2022; 10(1):1-23.

¹⁴ Gavriatopoulou M, et al. Metabolic Disorders in Multiple Myeloma. Int J Mol Sci. 2021; 22(21):11430.

¹⁵ American Cancer Society. Multiple Myeloma: Early Detection, Diagnosis and Staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf . Last accessed: June 2025.

¹⁶ J&J Data on File (RF-452129). Number of patients treated with DARZALEX worldwide as of December 2024.

¹⁷ Janssen EMEA. European Commission Grants Marketing Authorisation for DARZALEX^® (Daratumumab) Subcutaneous Formulation for All Currently Approved Daratumumab Intravenous Formulation Indications. Available at: http://www.businesswire.com/news/home/20200604005487/en/European-Commission-GrantsMarketingAuthorisation-for-DARZALEX%C2%AE%E2%96%BC-daratumumab-SubcutaneousFormulation-for-all-CurrentlyApproved-Daratumumab-Intravenous-Formulation-Indications . Last accessed: June 2025.

¹⁸ Moreau P, et al. Bortezomib, Thalidomide, and Dexamethasone With or Without Daratumumab Before and After Autologous Stem-cell Transplantation for Newly Diagnosed Multiple Myeloma (CASSIOPEIA): A Randomised, Open label, Phase 3 study. Lancet. 2019; 394(10192):29-38.

¹⁹ Facon T, et al. MAIA Trial Investigators. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019; 380(22):2104-2115.

²⁰ Mateos MV, et al. Overall Survival with Daratumumab, Bortezomib, Melphalan, and Prednisone in Newly Diagnosed Multiple Myeloma (ALCYONE): A Randomised, Open-label, Phase 3 trial. The Lancet. 2020; 395:132-141.

²¹ Dimopoulos MA, et al. APOLLO Trial Investigators. Daratumumab plus Pomalidomide and Dexamethasone versus Pomalidomide and Dexamethasone Alone in Previously Treated Multiple Myeloma (APOLLO): An Open-label, Randomised, Phase 3 trial. Lancet Oncol. 2021; 22(6):801-812.

²² Palladini G, et al. Daratumumab plus CyBorD for Patients with Newly Diagnosed AL Amyloidosis: Safety Run-in Results of ANDROMEDA. Blood. 2020; 136(1):71-80.

²³ Chari A, et al. Daratumumab plus Pomalidomide and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma. Blood. 2017; 130(8):974-981.

²⁴ Bahlis NJ, et al. Daratumumab plus Lenalidomide and Dexamethasone in Relapsed/refractory Multiple Myeloma: Extended Follow-up of POLLUX, a Randomized, Open-label, Phase 3 study. Leukemia. 2020; 34(7):1875-1884.

²⁵ Mateos MV, et al. Daratumumab, Bortezomib, and Dexamethasone versus Bortezomib and Dexamethasone in Patients with Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR. Clin Lymphoma Myeloma Leuk. 2020; 20(8):509-518.

²⁶ Usmani SZ, et al. Daratumumab + Bortezomib/Lenalidomide/Dexamethasone in Patients with Transplant-ineligible or Transplant-deferred Newly Diagnosed Multiple Myeloma: Results of the Phase 3 CEPHEUS study. Oral presentation. 21^st International Myeloma Society (IMS) Annual Meeting. September 25 – 28, 2024.