Johnson & Johnson submits applications in the U.S. and EU seeking approval of DARZALEX FASPRO®/DARZALEX® (daratumumab) as subcutaneous monotherapy for high-risk smouldering multiple myeloma

If approved, daratumumab will become the first treatment option for patients with smouldering multiple myeloma at high-risk of developing multiple myeloma, offering a novel approach to treat before the onset of active disease and the occurrence of end organ damage¹

BEERSE, BELGIUM, Nov. 08, 2024 (GLOBE NEWSWIRE) --  Janssen-Cilag International NV, a Johnson & Johnson company, today announced the submission of regulatory applications to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) seeking approval of a new indication for DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) in the U.S. and DARZALEX^® (daratumumab) subcutaneous (SC) formulation in the European Union (EU). The applications are supported by data from the ongoing Phase 3 AQUILA study (NCT03301220) of daratumumab SC as monotherapy for the treatment of adult patients with high-risk smouldering multiple myeloma.²

Smouldering multiple myeloma is an early precursor of active multiple myeloma, where abnormal cells can be detected in the bone marrow, but patients are typically asymptomatic.¹ Fifteen percent of all cases of newly diagnosed multiple myeloma are classified as smouldering multiple myeloma, and half of those diagnosed with high-risk disease will progress to active multiple myeloma within two years.³ Currently, smouldering multiple myeloma is not generally treated until active multiple myeloma develops. Instead, the standard approach is observation to track the disease for signs of biochemical progression and/or end organ damage, when treatment tends to be initiated.¹ Recent evidence suggests that those at high-risk for progression to active multiple myeloma could benefit from earlier therapeutic intervention.⁴

“There remains an unmet need for early interventions and treatments that are both effective and well tolerated in people living with smouldering multiple myeloma at high-risk of progressing to active multiple myeloma,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D. Global Therapeutic Area Head, Oncology, Innovative Medicine, Johnson & Johnson. “Daratumumab has changed the standard of care in multiple myeloma and with these submissions to the FDA and EMA, this therapy could become the first approved treatment for patients with high-risk smouldering multiple myeloma, potentially shifting the treatment paradigm.”

The first data from the AQUILA study, evaluating the safety and efficacy of 3 years fixed duration daratumumab SC compared to active monitoring in participants with high-risk smouldering multiple myeloma, will be presented at the 2024 American Society of Hematology (ASH) Annual Meeting, taking place in San Diego from December 7-10.⁴

About the AQUILA Study
AQUILA (NCT03301220) is a randomised, multicentre Phase 3 study investigating daratumumab SC versus active monitoring in patients (n=390) with high-risk smouldering multiple myeloma.² The primary endpoint is progression free survival and secondary endpoints include time to progression, overall response rate and overall survival.² Patients in the study were diagnosed with smouldering multiple myeloma in the last five years and were excluded if they had prior exposure to approved or investigational treatments for smouldering multiple myeloma or multiple myeloma.²

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 548,000 patients worldwide.⁵ Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma.⁶ Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE^® drug delivery technology.⁷

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.⁸ Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death.⁸ Daratumumab may also have an effect on normal cells.⁸ 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.^{9,10,11,12,13,14,15,16,17,18}

For further information on daratumumab, please see the Summary of Product Characteristics at: https://www.ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf.

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.^19,20 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 complications.²⁰ 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.²¹ 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.²²

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 Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Research & Development, LLC and/or 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 Annual Report on Form 10-K for the fiscal year ended December 31, 2023, 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. None of Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Research & Development, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

¹ Myeloma UK. Smouldering myeloma. Accessed: October 2024. Available at: https://www.myeloma.org.uk/understanding-myeloma/related-conditions/smouldering-myeloma/#:~:text=In%20smouldering%20myeloma%20abnormal%20cells,generally%20do%20not%20require%20treatment.

² ClinicalTrials.Gov. A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma. Accessed: October 2024. Available at: Study Details | A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma | ClinicalTrials.gov

³ Rajkumar SV, Kumar S, Lonial S, Mateos MV. Smoldering multiple myeloma current treatment algorithms. Blood Cancer J. 2022 Sep 5;12(9):129.

⁴ M.A. Dimopoulos, 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. Presented at the December 2024 ASH Annual Meeting & Exposition. Abstract JJD-78127.

⁵ Johnson & Johnson [data on file]. RF-430506. Number of patients treated with DARZALEX^® worldwide as of 30 June 2024.

⁶ Sonneveld P, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2024; 390:301-313.

⁷Janssen EMEA. European Commission Grants Marketing Authorisation for DARZALEX^® (Daratumumab) Subcutaneous Formulation for All Currently Approved Daratumumab Intravenous Formulation Indications. Available at: 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: October 2024.

⁸ European Medicines Agency. DARZALEX (daratumumab) Summary of Product Characteristics. October 2024.

⁹ 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, openlabel, phase 3 study. Lancet 2019;394(10192):29-38.

¹⁰ Facon T, et al. MAIA Trial Investigators. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med 2019;380(22):2104-2115.

¹¹ 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:P132-141.

¹² 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.

¹³ Palladini G, et al. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood 2020;2;136(1):71-80.

¹⁴ Chari A, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 2017;130(8):974-981.

¹⁵ 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.

¹⁶ 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.

¹⁷ Sonneveld, P. et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2024;390(4):301-313. DOI: 10.1056/NEJMoa23120

¹⁸ Usmani, S Z. 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.

¹⁹ Abdi J, et al. Drug resistance in multiple myeloma: latest findings on molecular mechanisms. Oncotarget 2013;4(12):2186-2207.

²⁰ American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Last accessed: October 2024.

²¹ 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: October 2024.

²² 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: October 2024.

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November 2024