• Combination regi­men reduces the risk of dis­ease pro­gres­sion or death by 44 per­cent in newly diag­nosed patients who are trans­plant in­eli­gible¹
• Since launch, dara­tu­mu­mab has been used to treat more than 100,000 patients world­wide²

Beerse, Belgium (Press Release) – The Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson announced today that the European Com­mis­sion (EC) has granted mar­ket­ing authori­sa­tion for Darzalex®(dara­tu­mu­mab) in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (DRd) for the treat­ment of newly diag­nosed multiple myeloma patients who are in­eli­gible for au­tol­o­gous stem cell trans­plant (ASCT). The approval was based on results from the Phase 3 MAIA (MMY3008) study, published in The New England Journal of Medicine³ earlier this year and presented at the American Society of Hematology (ASH) Annual Meeting in 2018.

“Despite recent thera­peutic ad­vances, relapse of multiple myeloma is con­sidered to be almost in­evi­table, becoming more chal­leng­ing to treat fol­low­ing each relapse. This makes it even more im­por­tant that we maximise our best re­sponse­ up­front to extend the first remission,” said Pro­fessor Thierry Facon, M.D., Service des Maladies du Sang, Hôspital Claude Huriez, Lille, France, and prin­ci­pal investigator of the MAIA study. “This marks an im­por­tant approval, especially for trans­plant in­eli­gible patients, a more vulnerable pop­u­la­tion, for whom out­comes are generally poorer when com­pared to those who are trans­plant eli­gible.”

The study in­cluded 737 newly diag­nosed patients with multiple myeloma in­eli­gible for high-dose chemo­ther­apy and ASCT aged 45-90 years old (median age of 73 years).¹ Dara­tu­mu­mab in com­bi­na­tion with Rd sig­nif­i­cantly reduced the risk of dis­ease pro­gres­sion or death by 44 per­cent in patients with newly diag­nosed multiple myeloma who are trans­plant in­eli­gible, com­pared to treat­ment with Rd alone (Hazard Ratio [HR] = 0.56; 95 per­cent con­fi­dence in­ter­val [CI]: 0.43-0.73; p<0.0001).¹ At median follow-up of 28.0 months the median pro­gres­sion-free sur­vival (PFS) for dara­tu­mu­mab-Rd had not yet been reached, com­pared to 31.9 months for patients who re­ceived Rd alone.¹ The addi­tion of dara­tu­mu­mab resulted in deeper re­sponse­s com­pared to Rd alone, in­clud­ing in­creased rates of com­plete re­sponse­ (CR) or better (48 per­cent vs. 25 per­cent) and im­proved rates of very good partial re­sponse­ (VGPR) or better (79 per­cent vs. 53 per­cent).¹ Dara­tu­mu­mab-Rd induced a >3-fold higher rate of minimal residual dis­ease (MRD) negativity com­pared to those who re­ceived Rd alone (24 per­cent vs. 7 per­cent).¹

“Every year over 48,000 people in Europe are diag­nosed with multiple myeloma, which is con­sidered to be incurable. Older patients who are in­eli­gible for trans­plant have a limited range of front­line thera­peutic options avail­able, so we are pleased that with today’s approval of dara­tu­mu­mab-Rd, these patients now have a new front­line option avail­able to them,” said Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag.

Craig Tendler, M.D., Vice Pres­i­dent, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC., commented: “It’s grat­i­fy­ing to see that through our re­search and devel­op­ment efforts, dara­tu­mu­mab has helped over 100,000 patients globally. With today’s approval and the con­tinued devel­op­ment of dara­tu­mu­mab, we hope to bring this inno­va­tive ther­apy to many more patients in the future.”

The most common Grade 3/4 treat­ment-emergent adverse events (TEAEs) for dara­tu­mu­mab-Rd (≥10 per­cent) in­cluded neu­tro­penia (50 per­cent), lymphopenia (15 per­cent), pneu­monia (14 per­cent) and anaemia (12 per­cent).¹ Infusion-related reac­tions (IRRs) occurred in 41 per­cent of patients, only 3 per­cent of which were Grade 3/4.¹ Incidence of in­vasive second pri­mary malig­nan­cy was 3 per­cent in the dara­tu­mu­mab-Rd arm com­pared to 4 per­cent with Rd alone.¹ TEAEs with an out­come of death were 7 per­cent in the dara­tu­mu­mab-Rd arm com­pared to 6 per­cent in the Rd arm.¹ The safety profile of dara­tu­mu­mab was con­sis­tent with that of pre­vi­ous studies.¹

In Europe, dara­tu­mu­mab is in­di­cated:⁴

• in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of adult patients with newly diag­nosed multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant,
• in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, or bor­tez­o­mib and dexa­meth­a­sone, for the treat­ment of adult patients with multiple myeloma who have re­ceived at least one prior ther­apy,
• as mono­therapy for the treat­ment of adult patients with re­lapsed and re­frac­tory multiple myeloma, whose prior ther­apy in­cluded a pro­te­a­some in­hib­i­tor (PI) and an immuno­modu­la­tory agent, and who have dem­onstrated dis­ease pro­gres­sion on the last ther­apy.

About the MAIA (NCT02252172) Trial⁵

In this open-label and multicentre Phase 3 study patients were ran­domised to re­ceive either dara­tu­mu­mab-Rd or Rd alone in 28-day Cycles. In the dara­tu­mu­mab-Rd treat­ment arm, patients re­ceived dara­tu­mu­mab 16 (mg/kg) IV weekly for Cycles 1 – 2, every two weeks for Cycles 3 – 6 and every 4 weeks for Cycle 7 and there­after. The pri­mary end­point was Progression-Free Survival, defined as the time from date of ran­domisation to either progressive dis­ease, or death, whichever occurred first. Patients in the dara­tu­mu­mab-Rd and Rd treat­ment arm re­ceived 25 mg of lena­lido­mide on Days 1 – 21 of each 28-day Cycle, and dexa­meth­a­sone at 40 mg once a week for each Cycle. Patients in both treat­ment arms con­tinued until dis­ease pro­gres­sion or unacceptable toxicity.

About dara­tu­mu­mab

Daratumumab is a first-in-class⁶ biologic targeting CD38, a surface protein that is highly ex­pressed across multiple myeloma cells, re­gard­less of dis­ease stage.⁷ 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.⁴ A subset of myeloid derived sup­pressor cells (CD38+ MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) were de­creased by dara­tu­mu­mab.⁴ Since launch, it is esti­mated that 100,000 patients have been treated with dara­tu­mu­mab world­wide.² Dara­tu­mu­mab is being eval­u­ated in a com­pre­hen­sive clin­i­cal devel­op­ment pro­gramme across a range of treat­ment settings in multiple myeloma, such as in front­line and re­lapsed settings.^{5,8,9,10,11,12,13,14} Additional studies are ongoing or planned to assess its poten­tial in other malignant and pre-malignant haematologic dis­eases in which CD38 is ex­pressed, such as smoul­der­ing myeloma.^15,16 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.

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.¹⁷

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is char­ac­ter­ised by an excessive pro­lif­er­a­tion of plasma cells.¹⁸ In Europe, more than 48,200 people were diag­nosed with MM in 2018, and more than 30,800 patients died.¹⁹ Almost 60 per­cent of patients with MM do not sur­vive more than five years after diag­nosis.²⁰

Although treat­ment may result in remission, unfortunately, patients will most likely relapse as there is cur­rently no cure.²¹ Refractory MM is when a patient’s dis­ease progresses within 60 days of their last ther­apy.^22,23 Relapsed cancer is when the dis­ease has returned after a period of initial, partial or com­plete remission.²⁴ While some patients with MM have no symp­toms at all, most patients are diag­nosed due to symp­toms that can in­clude bone problems, low blood counts, cal­cium elevation, kidney problems or in­fec­tions.²⁵ Patients who relapse after treat­ment with standard ther­a­pies, in­clud­ing pro­te­a­some in­hib­i­tors and immuno­modu­la­tory agents, have poor prognoses and few treat­ment options avail­able.²⁶

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-Cilag, Janssen Biotech, Inc. and Janssen Research & Development, LLC 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 for the treat­ment of patients with multiple myeloma. 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 of the 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 30, 2018, 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 of Johnson & Johnson 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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Source: Janssen.