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Janssen Seeks Expanded Use of DARZALEX®▼ (daratumumab) Subcutaneous Formulation for the Treatment of Patients with Light Chain (AL) Amyloidosis

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the submission of a Type II variation application to the European Medicines Agency (EMA) seeking approval to expand the use of the DARZALEX® ▼ (daratumumab) subcutaneous (SC) formulation to include the treatment of patients with light chain (AL) amyloidosis.

AL amyloidosis is a rare and potentially fatal disease that occurs when an insoluble protein called amyloid builds up in tissues and organs, interfering with healthy tissue and organ function.3,4 There are currently no therapeutic options approved by regulatory bodies such as the EMA or the U.S. Food and Drug Administration (FDA) for treatment of the disease.1,2

The submission is based on data from the Phase 3 ANDROMEDA study, presented during the 2020 European Hematology Association (EHA) Annual Congress . The study evaluated the efficacy and safety of daratumumab SC in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd) compared with bortezomib, cyclophosphamide, and dexamethasone (VCd) alone in the treatment of patients with AL amyloidosis. The study data showed a significantly higher haematologic complete response rate for patients with the addition of daratumumab compared with patients treated with VCd alone.5 Overall, the safety profile of D-VCd demonstrated a consistent safety profile compared to the VCd regimen and the known safety profile of daratumumab.5

“The current management of AL amyloidosis focuses on slowing production of amyloid protein and controlling symptoms; however, there are no EMA-approved therapies for this difficult-to-treat, rare disease,” said Dr Catherine Taylor, VP, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd. Middle East. “If approved, adding daratumumab to this combination could address a significant unmet need and offer new hope to patients with AL amyloidosis, who have poor prognoses and have long been waiting for therapeutic options.”

“Daratumumab is an important foundational therapy in the treatment of multiple myeloma and now, on the basis of the ANDROMEDA study results, has shown that it can improve outcomes in a related plasma cell disorder, AL amyloidosis,” said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Janssen Research & Development, LLC. “We are excited about the potential for daratumumab, as part of a regimen for newly diagnosed patients with AL amyloidosis to alter the poor prognosis of their disease and reduce organ damage, which is an unfortunate life-threatening complication of this serious disease.”

In September 2020, Janssen submitted a supplemental Biologics Licence Application (sBLA) to the U.S. FDA seeking approval of the subcutaneous formulation of daratumumab for the treatment of patients with AL amyloidosis.6

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About the ANDROMEDA Study5,7

ANDROMEDA (NCT03201965 ) is an ongoing Phase 3, randomised, open-label study investigating the safety and efficacy of daratumumab SC in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd), compared to VCd alone, in the treatment of patients with newly diagnosed AL amyloidosis.5,7 The study includes 388 patients with newly diagnosed AL amyloidosis with measurable haematologic disease and one or more organs affected. The primary endpoint is overall complete haematologic response rate by intent-to-treat (ITT). Secondary endpoints include major organ deterioration, progression-free survival, major organ deterioration event free survival, organ response rate, overall survival, and time to haematologic response, among others.5,7

About AL Amyloidosis

Light chain (AL) amyloidosis is a rare and potentially fatal haematologic disorder that can affect the function of multiple organs.1,2 The disease occurs when bone marrow produces abnormal antibodies called light chains, which clump together to form a substance called amyloid. These clumps of amyloid are deposited in tissues and vital organs and interfere with normal organ function, eventually causing organ deterioration.1,2 AL amyloidosis is the most common type of amyloidosis. It frequently affects the heart, kidneys, digestive tract, liver and nervous system.1,2 Diagnosis is often delayed and prognosis is poor due to advanced, multi-organ, particularly cardiac, involvement. Approximately 30,000 to 45,000 patients in the European Union and the United States have AL amyloidosis.8

About daratumumab and daratumumab SC

Daratumumab is a first-in-class biologic targeting CD38, a surface protein that is highly expressed across multiple myeloma (MM) cells, regardless of disease stage.9,10 Daratumumab is believed to induce tumour cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.10 A subset of myeloid derived suppressor cells (CD38+ MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) are decreased by daratumumab-mediated cell lysis.10

In August 2012 , Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive licence to develop, manufacture and commercialise daratumumab.11 Since launch, it is estimated that more than 154,000 patients have been treated with daratumumab worldwide.12 In June 2020 , daratumumab SC (daratumumab and hyaluronidase human-fihj) was approved by the European Commission as the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma.13 Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.13

Daratumumab is being evaluated in a comprehensive clinical development programme across a range of treatment settings in MM, such as in frontline and relapsed settings.14,15,16,17,18,19,20,21 Additional studies are ongoing or planned to assess the potential of daratumumab SC in other malignant and pre-malignant haematologic diseases in which CD38 is expressed, such as smouldering myeloma and AL amyloidosis.22,23 For more information, please see https://www.clinicaltrials.gov/ .

For further information on daratumumab, please see the Summary of Product Characteristics at https://www.ema.europa.eu/en/medicines/human/EPAR/darzalex .

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com/emea . Follow us at www.twitter.com/janssenEMEA for our latest news. Janssen Research & Development, LLC, Janssen-Cilag Limited Middle East, and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

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Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding the benefits of daratumumab subcutaneous formulation for the treatment of patients with light chain amyloidosis. 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 Pharmaceutica N.V., Janssen Pharmaceutical Companies 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; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; 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 29, 2019, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov , www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

ENHANZE® is a registered trademark of Halozyme.

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References

1. Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, Quellard N, Lacombe C, Goujon JM, Lavergne D, Abraham J. AL amyloidosis. Orphanet journal of rare diseases. 2012 Dec;7(1):54

2. Merlini G, Comenzo RL, Seldin DC, Wechalekar A, Gertz MA. Immunoglobulin light chain amyloidosis. Expert review of hematology. 2014 Feb 1;7(1):143-56.

3. Stat Pearls. Amyloidosis. Available at: https://www.ncbi.nlm.nih.gov/books/NBK470285/ . Last accessed: November 2020.

4. Mayo Clinic. Amyloidosis Overview: Symptoms and Causes. Available at: https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178 Last accessed: November 2020.

5. Kastritis, E. et al. Subcutaneous Daratumumab + Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) in Patients with Newly Diagnosed Light Chain (AL) Amyloidosis: Primary Results from the Phase 3 ANDROMEDA Study [LBA]. To be presented at European Hematology Association 2020 Annual Congress.

6. Janssen Pharmaceutical Companies of Johnson & Johnson. Janssen Submits Application Seeking U.S. FDA Approval of DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) for the Treatment of Patients with Light Chain (AL) Amyloidosis. Available at: https://www.prnewswire.com/news-releases/janssen-submits-application-seeking-us-fda-approval-of-darzalex-faspro-daratumumab-and-hyaluronidase-fihj-for-the-treatment-of-patients-with-light-chain-al-amyloidosis-301126998.html Last accessed: November 2020.

7. ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis. NCT03201965. Available at: https://clinicaltrials.gov/ct2/show/NCT03201965 Last accessed: November 2020.

8. Lousada I, Comenzo RL, Landau H, Guthrie S, Merlini G. Light chain amyloidosis: patient experience survey from the Amyloidosis Research Consortium. Advances in therapy. 2015 Oct 1;32(10):920-8.

9. 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: November 2020.

10. Sanchez L, Wang Y, Siegel DS, Wang ML. Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma. J Hematol Oncol . 2016;9:51.

11. Johnson & Johnson. Janssen Biotech announces global license and development agreement for investigational anti-cancer agent daratumumab. Press release August 30, 2012. Available at: https://www.jnj.com/media-center/press-releases/janssen-biotech-announces-global-license-and-development-agreement-for-investigational-anti-cancer-agent-daratumumab Last accessed: November 2020.

12. [Data on file]. DARZALEX: New Patient Starts Launch to Date. RF-145436

13. Janssen EMEA. European Commission Grants Marketing Authorisation for DARZALEX®▼(daratumumab) Subcutaneous Formulation for all Currently Approved Daratumumab Intravenous Formulation Indications. Press Release June 04, 2020. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/european_commission_grants_marketing_authorisation_for_darzalexrvdaratumumab_subcutaneous_formulation_for_all_currently_approved_daratumumab_intravenous_formulation_indications.pdf Last accessed: November 2020.

14. ClinicalTrials.gov. A study to evaluate daratumumab in transplant eligible participants with previously untreated multiple myeloma (Cassiopeia). NCT02541383. Available at: https://clinicaltrials.gov/ct2/show/NCT02541383 Last accessed: November 2020

15. ClinicalTrials.gov. A study comparing daratumumab, lenalidomide, and dexamethasone with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma. NCT02076009. Available at: https://clinicaltrials.gov/ct2/show/NCT02076009 Last accessed: November 2020.

16. ClinicalTrials.gov. Addition of daratumumab to combination of bortezomib and dexamethasone in participants with relapsed or refractory multiple myeloma. NCT02136134. Available at: https://clinicaltrials.gov/ct2/show/NCT02136134 Last accessed: November 2020.

17. ClinicalTrials.gov. A study of combination of daratumumab and Velcade (bortezomib) melphalan-prednisone (DVMP) compared to Velcade melphalan-prednisone (VMP) in participants with previously untreated multiple myeloma. NCT02195479. Available at: https://clinicaltrials.gov/ct2/show/NCT02195479 Last accessed: November 2020.

18. ClinicalTrials.gov. Study comparing daratumumab, lenalidomide, and dexamethasone with lenalidomide and dexamethasone in participants with previously untreated multiple myeloma. NCT02252172. Available at: https://clinicaltrials.gov/ct2/show/NCT02252172 Last accessed: November 2020.

19. ClinicalTrials.gov. A study of Velcade (bortezomib) melphalan-prednisone (VMP) compared to daratumumab in combination with VMP (D-VMP), in participants with previously untreated multiple myeloma who are ineligible for high-dose therapy (Asia Pacific region). NCT03217812. Available at: https://clinicaltrials.gov/ct2/show/NCT03217812 Last accessed: November 2020.

20. ClinicalTrials.gov. Comparison of pomalidomide and dexamethasone with or without daratumumab in subjects with relapsed or refractory multiple myeloma previously treated with lenalidomide and a proteasome inhibitor daratumumab/pomalidomide/dexamethasone vs pomalidomide/dexamethasone (EMN14). NCT03180736. Available at: https://clinicaltrials.gov/ct2/show/NCT03180736 Last accessed: November 2020.

21. ClinicalTrials.gov. Study of carfilzomib, daratumumab and dexamethasone for patients with relapsed and/or refractory multiple myeloma (CANDOR). NCT03158688. Available at: https://clinicaltrials.gov/ct2/show/NCT03158688 Last accessed: November 2020.

22. ClinicalTrials.gov. A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma. NCT03301220. Available at: https://clinicaltrials.gov/ct2/show/NCT03301220 Last accessed: November 2020.

23. ClinicalTrials.gov. A Study of Daratumumab Monotherapy in Previously Untreated Patients With Stage 3B Light Chain (AL) Amyloidosis. NCT04131309. Available at: https://clinicaltrials.gov/ct2/show/NCT04131309 Last accessed: November 2020.

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