JANSSEN-PHARMACEUTICAL

The Janssen Pharmaceutical Companies of Johnson & Johnson announced today new data from the Phase 3 ANDROMEDA study, which evaluated DARZALEX^® ▼ (daratumumab) subcutaneous (SC) formulation in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) as a treatment for patients with light chain (AL) amyloidosis, a rare disease associated with deterioration of vital organs, most notably the heart, kidneys and liver, for which there are no currently approved therapies.^1,2 The data, which were featured in an oral presentation at the American Society of Hematology (ASH) 2020 Annual Meeting, showed a significantly higher complete haematologic response rate with D-VCd treatment in patients with this potentially fatal blood disorder compared to the standard regimen and consistent decreases in markers of disease, indicative of deep haematologic responses (Abstract #552).³

These data supported the recent submissions to the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) seeking approval for daratumumab SC for the treatment of patients with AL amyloidosis. The submissions are being reviewed by the EMA and FDA to seek the first approval for any drug in this disease.^4,5

“AL amyloidosis is a rare blood disease in which abnormal proteins build up in the tissues and organs and eventually cause major organ deterioration,” said study investigator, Raymond L. Comenzo, M.D.,* Director, John C. Davis Myeloma and Amyloid Program, Tufts Medical Center and ANDROMEDA study investigator. “The data being presented at ASH show the potential of this new treatment regimen. Compared to VCd alone, D-VCd increased haematologic response rates and prolonged major organ deterioration-progression-free survival (MOD-PFS).”

Key Findings from the ANDROMEDA Oral Presentation Abstract #552:

• The primary endpoint of the Phase 3 ANDROMEDA study was complete haematologic response rate, defined as normalisation of the free light chain (FLC) and serum free light chain ratio (FCLr) and negative serum and urine immunofixation.³ The overproduction of light chains by plasma cells leads to the deposit of an abnormal protein called amyloid in major organs, interfering with their function.^6,7
• The data showed that haematologic response rates were higher in patients with newly diagnosed AL amyloidosis who were treated with D-VCd compared to VCd alone (53 percent vs. 18 percent, respectively), a current treatment regimen offered to patients with AL amyloidosis.³
• Results consistently favour the daratumumab-containing regimen across various measures of deep haematological response:
  • Haematological response based upon iFLC ≤20 mg/L (regardless of FLC ratio) favoured D-VCd vs. VCd (71 percent vs. 20 percent).³
  • Haematological response based upon the difference between iFLC and uninvolved FLC (dFLC)<10 mg/L (regardless of FLC ratio) favoured D-VCd vs. VCd (64 percent vs. 31 percent).³
  • MOD-PFS was longer in patients treated with D-VCd who achieved deep haematologic response by all criteria including complete haematological response, low iFLC, low dFLC.³

Additionally, D-VCd had an acceptable safety profile, consistent with that previously observed for each of the agents alone.³

“AL amyloidosis is a challenging disease to diagnose and treat, with symptoms that mimic other conditions. Due to delayed diagnosis, major organ deterioration can occur,” said Jessica Vermeulen, M.D., Ph.D., Global Medical Head/Clinical Leader, Hematology & Oncology, Janssen Research & Development, LLC. “It is our hope that the ANDROMEDA study contributes to raising awareness of AL amyloidosis among patients and providers, and that, pending health authority reviews, approval of daratumumab SC will bring a much-needed and effective treatment option to patients.”

“We are encouraged by these results, which show that a daratumumab-based combination therapy can offer new hope to patients living with the rare blood disease of AL amyloidosis and address a significant unmet need,” said Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. “If approved, it could offer new hope to patients living with AL amyloidosis and address a significant unmet need.”

Extent of cardiac involvement at baseline has a major impact on clinical outcomes for patients with AL amyloidosis.⁸ A separate poster presentation of the ANDROMEDA data focused on the impact of cardiac involvement in newly diagnosed AL amyloidosis patients (Abstract #1392).⁸ Results found the rates of haematologic, cardiac and renal response at six months were higher in the D-VCd group than in the VCd group regardless of baseline cardiac stage (I, II or III) with more than 76 percent of these patients having a baseline cardiac stage of II or higher.⁸ Additionally, both MOD-PFS and major organ deterioration-event-free survival (MOD-EFS) favored D-VCd across baseline cardiac stages.⁸

*Raymond L. Comenzo, M.D., is lead investigator of the ANDROMEDA study and was not compensated for any media work.

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About the ANDROMEDA Study
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.^9,10 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. 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.^9,10

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.^11,12 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.^11,12 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.^11,12

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.¹³ Since launch, it is estimated that more than 154,000 patients have been treated with daratumumab worldwide.¹⁴ 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.¹⁵ Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE^® drug delivery technology.¹⁵

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.^{16,17,18,19,20,21,22,23} 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.^24,25 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 AL amyloidosis
Light chain (AL) amyloidosis is a rare and potentially fatal haematologic disorder that can affect the function of multiple organs.^6,7 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.^6,7 AL amyloidosis is the most common type of systemic amyloidosis.¹ It frequently affects the heart, kidneys, digestive tract, liver and nervous system.^6,7 Diagnosis is often delayed and prognosis is poor due to advanced, multi-organ, particularly cardiac, involvement.^6,7 Approximately 30,000 to 45,000 patients in the European Union and the United States have AL amyloidosis.²

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 Ltd., Middle East, and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

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 materialize, actual results could vary materially from the expectations and projections of Janssen Pharmaceutica NV, 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. Neither 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.

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References:

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¹ National Organization for Rare Disorders. Amyloidosis. Available at: https://rarediseases.org/rare-diseases/amyloidosis/. Last accessed December 2020.
² Lousada I, et al., Light chain amyloidosis: patient experience survey from the Amyloidosis Research Consortium. Advances in Therapy. 2015;32(10):920-928.
³ Comenzo, RL et al., Reduction in Absolute Involved Free Light Chain and Difference Between Involved and Uninvolved Free Light Chain Is Associated with Prolonged Major Organ Deterioration Progression-Free Survival in Patients with Newly Diagnosed AL Amyloidosis Receiving Bortezomib, Cyclophosphamide, and Dexamethasone With or Without Daratumumab: Results From ANDROMEDA. Abstract #552. To be presented at 2020 American Society of Hematology Annual Meeting.
⁴ Janssen Seeks Expanded Use of DARZALEX®▼ (daratumumab) Subcutaneous Formulation for the Treatment of Patients with Light Chain (AL) Amyloidosis. Janssen, 5 Nov. 2020. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/janssen_seeks_expanded_use_of_darzalexrv_daratumumab_subcutaneous_formulation_for_the_treatment_of_patients_with_light_chain_al_amyloidosis.pdf . Last accessed: December 2020.
⁵ Janssen. 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.janssen.com/janssen-submits-application-seeking-us-fda-approval-darzalex-faspro-daratumumab-and-hyaluronidase Last accessed: December 2020.
⁶ Desport E et al. AL amyloidosis. Orphanet journal of rare diseases. 2012 Dec;7(1):54.
⁷ Merlini G et al. Immunoglobulin light chain amyloidosis. Expert review of hematology. 2014 Feb 1;7(1):143-56.
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December 2020

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