• If approved by the European Com­mis­sion, the dara­tu­mu­mab-VTd regi­men would rep­re­sent the first thera­peutic option in­di­cated for newly diag­nosed patients who are eli­gible for a stem cell trans­plant in six years¹
• 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 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 bor­tez­o­mib, thalido­mide and dexa­meth­a­sone (VTd) for the treat­ment of adult patients with newly diag­nosed patients with multiple myeloma who are eli­gible for au­tol­o­gous stem cell trans­plant (ASCT).

The Positive Opinion is sup­ported by data from Part 1 of the Phase 3 CASSIOPEIA (MMY3006) study, pub­lished in The Lancet³ in June 2019, and pre­sented at the 2019 American Society of Clinical Oncology (ASCO) Meeting. Additional in­for­ma­tion about this study can be found at www.ClinicalTrials.gov (NCT02541383).

“Today’s Opinion takes us a step closer to offering the first dara­tu­mu­mab com­bi­na­tion regi­men to trans­plant eli­gible patients, redefining treat­ment for those people newly diag­nosed with multiple myeloma,” said Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. “We are com­mit­ted to de­livering ad­vances in multiple myeloma care, in­clud­ing providing inno­va­tive treat­ment options that meet the evolving needs of people living with this dis­ease.”

Craig Tendler, M.D., Vice Pres­i­dent, Clinical Development and Global Medical Affairs, Oncology at Janssen Research & Development, LLC., commented: “Our robust clin­i­cal devel­op­ment pro­gramme con­tinues to dem­onstrate that dara­tu­mu­mab provides a foundation for the treat­ment of patients with multiple myeloma across the treat­ment con­tin­uum.”

The CHMP’s Positive Opinion comes after the US Food and Drug Admin­istra­tion’s approval in Sep­tem­ber 2019. It will now be reviewed by the European Com­mis­sion, which has the authority to grant mar­ket­ing authori­sa­tion for med­i­cines in the European Economic Area.

In Europe, dara­tu­mu­mab is in­di­cated:⁴

• in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone or 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 and an immuno­modu­la­tory agent and who have dem­onstrated dis­ease pro­gres­sion on the last ther­apy

About the CASSIOPEIA Trial⁵

The ran­domised, open-label, multicentre, Phase 3 study is sponsored by the French Intergroupe Francophone du Myelome in col­lab­o­ration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology and Janssen Research & Development, LLC. The study in­cluded 1,085 newly diag­nosed patients with pre­vi­ously untreated, symp­tomatic multiple myeloma who were eli­gible for high-dose chemo­ther­apy and stem cell trans­plant. In the first part of the study, patients were ran­domised to re­ceive induction treat­ment with VTd alone or in com­bi­na­tion with dara­tu­mu­mab, high-dose ther­apy and ASCT, and con­sol­i­da­tion ther­apy with VTd alone or in com­bi­na­tion with dara­tu­mu­mab. The pri­mary end­point in this part of the study is the proportion of patients who achieve an sCR 100 days after trans­plant. In the second part of the study, which is ongoing, patients who achieved a partial re­sponse­ or better in part one will undergo a second ran­domisation to re­ceive main­te­nance treat­ment with dara­tu­mu­mab 16 mg/kg every eight weeks for up to two years or will be observed with no further treat­ment. The pri­mary end­point in this part of the study is pro­gres­sion-free sur­vival (PFS).

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 (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 Research & Development, LLC 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 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.

References

1. Johnson & Johnson. European Com­mis­sion Approves VELCADE® As A Frontline Induction Therapy Before Stem Cell Transplantation. Press release August 8, 2013. Available at: https://www.jnj.com/media-center/press-releases/european-commission-approves-velcade-as-a-frontline-induction-therapy-before-stem-cell-transplantation Last accessed De­cem­ber 2019.
2. Janssen. Data on file: RF-82203. Dara­tu­mu­mab: New patient starts launch to date. No­vem­ber 2019
3. Moreau P, Attal M, Hulin C, et al. Bor­tez­o­mib, thalido­mide, and dexa­meth­a­sone with or without dara­tu­mu­mab before and after au­tol­o­gous stem-cell trans­plan­ta­tion for newly diag­nosed multiple myeloma (CASSIOPEIA): a ran­domised, open-label, phase 3 study. Lancet. 2019;394:29-38.
4. European Medicines Agency. DARZALEX summary of prod­uct char­ac­ter­istics, No­vem­ber 2019. Available at: https://ec.europa.eu/health/documents/community-register/2019/20191119146548/anx_146548_en.pdf Last accessed De­cem­ber 2019.
5. 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 De­cem­ber 2019.
6. 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.
7. Fedele G, di Girolamo M, Recine U, et al. CD38 ligation in periph­eral blood mononuclear cells of myeloma patients induces release of protumorigenic IL-6 and im­paired secretion of IFNgamma cytokines and pro­lif­er­a­tion. Mediat Inflamm. 2013;2013:564687.
8. 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 De­cem­ber 2019.
9. 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 De­cem­ber 2019.
10. 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 De­cem­ber 2019.
11. 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 De­cem­ber 2019.
12. 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 De­cem­ber 2019.
13. 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 De­cem­ber 2019.
14. 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 De­cem­ber 2019.
15. ClinicalTrials.gov. A study to eval­u­ate 3 dose schedules of dara­tu­mu­mab in par­tic­i­pants with smol­der­ing multiple myeloma. NCT02316106. Available at: https://clinicaltrials.gov/ct2/show/NCT02316106 Last accessed De­cem­ber 2019.
16. ClinicalTrials.gov. An efficacy and safety proof of concept study of dara­tu­mu­mab in re­lapsed / refractory mantle cell lym­phoma, diffuse large B-cell lym­phoma, and follicular lym­phoma. NCT02413489. Available at: https://clinicaltrials.gov/ct2/show/NCT02413489 Last accessed De­cem­ber 2019.
17. 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 De­cem­ber 2019.
18. American Society of Clinical Oncology. Multiple myeloma: in­tro­duc­tion. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction Last accessed De­cem­ber 2019.
19. GLOBOCAN 2018. Cancer Today Population Factsheets: Europe Region. Available at: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf Last accessed De­cem­ber 2019.
20. De Angelis R, Minicozzi P, Sant M, et al. Survival variations by country and age for lymphoid and myeloid malig­nan­cies in Europe 2000-2007: results of EUROCARE-5 pop­u­la­tion-based study. Eur J Cancer. 2015;51:2254-68.
21. Abdi J, Chen G, Chang H, et al. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mech­a­nisms. Oncotarget. 2013;4:2186–207.
22. National Cancer Institute. NCI dictionary of cancer terms: re­frac­tory. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=350245 Last accessed De­cem­ber 2019.
23. Richardson P, Mitsiades C, Schlossman R, et al. The treat­ment of re­lapsed and re­frac­tory multiple myeloma. Hematology Am Soc Hematol Educ Program. 2007:317-23.
24. National Cancer Institute. NCI dictionary of cancer terms: re­lapsed. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45866 Last accessed De­cem­ber 2019.
25. American Cancer Society. Multiple myeloma: early detection, diag­nosis and staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf Last accessed De­cem­ber 2019.
26. Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of pro­gres­sion and sur­vival in multiple myeloma relapsing after ther­apy with IMiDs and bor­tez­o­mib: a multi­center inter­na­tional myeloma work­ing group study. Leukemia. 2012;26:149-57.

Source: Janssen.