Application sup­ported by the Phase 3 MAIA study for dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients newly diag­nosed with multiple myeloma who are in­eligible for au­tol­o­gous stem cell trans­plant

Beerse, Belgium (Press Release) – The Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson today announced the sub­mission of a Type II variation appli­ca­tion to the European Medicines Agency (EMA) for DARZALEX®▼ (dara­tu­mu­mab) in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (Rd) for the treat­ment of patients newly diag­nosed with multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant (ASCT).

“Today’s sub­mission brings us one step closer to our goal of im­prov­ing treat­ment out­comes for people newly diag­nosed with multiple myeloma,” said José Antonio Burón Vidal, VP Medical Affairs, Europe, Middle East and Africa (EMEA), Janssen-Cilag Limited. “We are incredibly grateful to the patients and investigators who par­tic­i­pated in the MAIA clin­i­cal trial pro­gramme and look for­ward to work­ing closely with the regu­la­tory author­i­ties to secure approval of this new com­bi­na­tion.”

The sub­mission is sup­ported by data from the Phase 3 MAIA (MMY3008) study, which were pre­sented at the 60th Annual Meeting of the American Society of Hematology.¹ The study showed that at a median follow-up of 28 months, dara­tu­mu­mab-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 The median pro­gres­sion-free survival (PFS) for dara­tu­mu­mab-Rd has 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 Within the study, patient health, functional capacity, symp­toms, psychosocial well-being, and life satisfaction were eval­u­ated through measures to assess change in health-related quality of life by the European Organisation for Research and Treat­ment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Euro Quality of Life (EQ-5D-5L) Health State Profile Utility Score.²

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 receiving dara­tu­mu­mab-Rd, 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.^1,3,4,5,6,7

Daratumumab-Rd is being reviewed by the U.S. Food and Drug Admin­istra­tion (FDA) under the Real-Time Oncology Review (RTOR) pilot pro­gramme.

In Europe, dara­tu­mu­mab is indicated:⁸

• 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
• as mono­therapy for the treat­ment of adult patients with re­lapsed and refractory multiple myeloma, whose prior ther­apy in­cluded a pro­te­a­some inhibitor and an immuno­modu­la­tory agent and who have dem­onstrated disease pro­gres­sion on the last ther­apy
• 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.

About the MAIA Trial²

The ran­domised, open-label, multicentre Phase 3 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). 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. 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-class biologic targeting CD38, a surface protein that is highly ex­pressed across multiple myeloma 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.¹¹ A subset of myeloid derived sup­pressor cells (CD38+ MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) were de­creased by dara­tu­mu­mab.¹¹ 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.^{2,12,13,14,15,16,17,18} 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.^19,20 For more in­for­ma­tion, please see www.clinicaltrials.gov.

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

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.²¹

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.²² In Europe, more than 48,200 people were diag­nosed with MM in 2018, and more than 30,800 patients died.²³ Up to half of newly diag­nosed patients do not reach five-year survival,24 and almost 29% of patients with MM will die within one year of diag­nosis.²⁵

Although treat­ment may result in remission, unfortunately, patients will most likely relapse as there is cur­rently no cure.²⁶ Refractory MM is when a patient’s disease progresses within 60 days of their last ther­apy.^27,28 Relapsed cancer is when the disease has returned after a period of initial, partial or com­plete remission.²⁹ 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.³⁰ Patients who relapse after treat­ment with standard ther­a­pies, in­­clud­ing pro­te­a­some inhibitors and immuno­modu­la­tory agents, have poor prognoses and few treat­ment options avail­able.³¹

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 Biotech, Inc., Janssen-Cilag Inter­na­tional NV, and Janssen-Cilag Limited 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 a recom­men­da­tion to broaden the existing mar­ket­ing authori­sa­tion for 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-Cilag Limited, Janssen Biotech, Inc., any of the Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson 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,” in the com­pany’s most recently filed Quarterly Report on Form 10-Q and in 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.

References

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Source: Janssen.