Beerse, Belgium (Press Release) – The Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson today announced that the Com­mit­tee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has rec­om­mended broadening the existing mar­ket­ing authori­sa­tion for Darzalex® (dara­tu­mu­mab) to in­clude the use of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (DRd) for patients with newly diag­nosed multiple myeloma (NDMM) who are in­eli­gible for au­tol­o­gous stem cell trans­plant (ASCT).

“As multiple myeloma can be­come more complex with each relapse, it is im­por­tant that patients receive the latest treat­ment options with the goal of extending their first remission period,” said Pro­fessor Thierry Facon, M.D., Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France, and prin­ci­pal investigator of the MAIA study. “For newly diag­nosed patients who are trans­plant in­eli­gible, this regi­men could be an im­por­tant frontline ther­apy option and reinforces the con­sis­tent clin­i­cal profile of dara­tu­mu­mab.”

This Positive Opinion is based on results from the Phase 3 MAIA (MMY3008) study, published in The New England Journal of Medicine,¹ and presented at the 2018 American Society of Hematology (ASH) Annual Meeting.

Additional in­for­ma­tion about the MAIA study can be found at www.ClinicalTrials.gov (NCT02252172).

“This recom­men­da­tion marks an im­por­tant step to­wards realising our ambition to im­prove out­comes for patients with multiple myeloma, right from diag­nosis, especially for the majority of patients who are not eli­gible for trans­plant,” said Craig Tendler, M.D., Vice Pres­i­dent, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC.

“Daratumumab has been used to treat more than 100,000 patients world­wide and we look for­ward to work­ing with regu­la­tory author­i­ties to bring this im­por­tant ther­apy to even more patients with multiple myeloma,” adds Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag France.

This Opinion will now be reviewed by the European Com­mis­sion (EC), which has the authority to grant final approval of the in­di­ca­tions.

Professor Thierry Facon was the prin­ci­pal investigator in the MAIA study. He was not compensated for any media work.

About the MAIA (NCT02252172) Trial²

The ran­domised, open-label, multicentre Phase 3 study in­cluded 737 NDMM patients in­eli­gible for high-dose chemo­ther­apy and ASCT aged 45-90 years old (median age of 73 years). 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 (PFS), defined as the time from date of ran­domisation to either progressive dis­ease (PD), 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-class³ biologic targeting CD38, a surface protein that is highly ex­pressed across multiple myeloma cells, re­gard­less of dis­ease stage.⁴ 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.5 A subset of myeloid derived sup­pressor cells (CD38+ MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) were de­creased by dara­tu­mu­mab.⁵ Since launch, it is esti­mated that 100,000 patients have been treated with dara­tu­mu­mab world­wide.⁶ 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.^{7,8,9,10,11,12,13,14} 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 www.clinicaltrials.gov.

The most frequent adverse reac­tions seen with dara­tu­mu­mab in­clude in­fusion reac­tions, fatigue, nausea, diarrhoea, muscle spasms, pyrexia, cough, neu­tro­penia, thrombo­cyto­penia, anaemia, periph­eral sensory neu­rop­athy and upper res­pira­tory tract in­fec­tion.⁵

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 (MM) 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.