Beerse, Belgium (Press Release) – Janssen-Cilag Inter­na­tional NV today announced the sub­mission of a Type II variation appli­ca­tion to the European Medicines Agency (EMA), for the immuno­therapy DARZALEX®▼ (dara­tu­mu­mab). The appli­ca­tion seeks to broaden the existing mar­ket­ing authori­sa­tion to in­clude dara­tu­mu­mab 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.

“This sub­mission to health author­i­ties takes us one step closer to our goal of redefining com­bi­na­tion ther­apy in multiple myeloma, with the poten­tial to make dara­tu­mu­mab avail­able to more patients through­out the treat­ment con­tin­uum: from newly diag­nosed, to heavily pre-treated,” said Dr Catherine Taylor, Haematology Therapeutic Area Lead, Janssen Europe, Middle East and Africa (EMEA). “We look for­ward to work­ing closely with the EMA through­out the review process to deliver on this ambition to optimise clin­i­cal benefits for multiple myeloma patients.”

The regu­la­tory sub­mission is now pending val­i­da­tion by the EMA and is sup­ported by data from the Phase 3 ALCYONE (MMY3007) study. Additional in­­for­ma­tion about this study can be found at www.ClinicalTrials.gov (NCT02195479), and study findings will be presented at the 59th Annual Meeting of the American Society of Hematology (ASH).

Daratumumab is cur­rently indicated for use 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;1 and as mono­therapy for the treat­ment of adult patients with re­lapsed and refractory multiple myeloma, whose prior ther­apy in­cluded a PI and an immuno­modu­la­tory agent, and who have dem­onstrated disease pro­gres­sion on the last ther­apy.¹

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.^2,3,4 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.¹ A subset of myeloid derived sup­pressor cells (MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) were de­creased by dara­tu­mu­mab.¹ Dara­tu­mu­mab is being eval­u­ated in a compre­hensive clin­i­cal develop­ment pro­gram that in­cludes nine Phase 3 studies across a range of treat­ment settings in multiple myeloma, such as in frontline and re­lapsed settings.^5-13 Additional studies are ongoing or planned to assess its poten­tial for a solid tumour indi­ca­tion and in other malignant and pre-malignant diseases in which CD38 is ex­pressed, such as smoulder­ing myeloma.^14-21 For more in­­for­ma­tion, please see www.clinicaltrials.gov.

For further in­­for­ma­tion on dara­tu­mu­mab, please see the Summary of Product Characteristics at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004077/WC500207296.pdf.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a world­wide agree­ment, which granted Janssen an exclusive license to develop, manu­fac­ture and commercialise dara­tu­mu­mab.

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 MM is the second most common form of blood cancer, with around 39,000 new cases world­wide in 2012.23 MM most commonly affects people over the age of 65 and is more common in men than in women.24 The most recent five-year survival data for 2000-2007 show that across Europe, up to half of newly diag­nosed patients do not reach five-year survival.25 Almost 29% of patients with MM will die within one year of diag­nosis.26

Although treat­ment may result in remission, unfortunately, patients will most likely relapse as there is cur­rently no cure.27 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.28 Patients who relapse after treat­ment with standard ther­a­pies, in­­clud­ing PIs and immuno­modulatory agents, have poor prognoses and few treat­ment options avail­able.29

About the Janssen Pharma­ceu­tical Com­panies

At the Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson, we are work­ing to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease in­spires us. We bring together the best minds and pursue the most promising science. We are Janssen. We col­lab­o­rate with the world for the health of everyone in it. Learn more at www.janssen.com/emea. Follow us at www.twitter.com/janssenEMEA for our latest news.

Cilag GmbH Inter­na­tional; Janssen Biotech, Inc.; Janssen Oncology, Inc. and Janssen-Cilag Inter­na­tional NV 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 poten­tial of dara­tumumab and ex­pec­ta­tions for its further develop­ment. 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-Cilag Inter­na­tional NV, any of the other 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 January 1, 2017, in­­clud­ing under “Item 1A. Risk Factors,” its most recently filed Quarterly Report on Form 10-Q, in­­clud­ing under the caption “Cautionary Note Regarding Forward-Looking Statements,” 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. None of the Janssen Pharma­ceu­tical Com­panies or Johnson & Johnson under­takes to update any for­ward-looking state­ment as a result of new in­­for­ma­tion or future events or devel­op­ments.

References

1. European Medicines Agency. DARZALEX summary of product characteristics, August 2017. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004077/WC500207296.pdf Last accessed November 2017.
2. 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.
3. Lin P, Owens R, Tricot G, et al. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121:482-8.
4. Santoconito AM, Consoli U, Bagnato S, et al. Flow cytometric detection of aneuploid CD38++ plasmacells and CD19+ B-lymphocytes in bone marrow, peripheral blood and PBSC harvest in multiple myeloma patients. Leuk Res. 2004;28:469-77.
5. 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 November 2017.
6. 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/results/NCT02136134 Last accessed November 2017.
7. 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 November 2017.
8. 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 November 2017.
9. 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 November 2017.
10.  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 November 2017.
11. ClinicalTrials.gov. Compare progression free survival btw daratumumab/​pomalidomide/​dexamethasone vs pomalidomide/​dexamethasone (EMN14). NCT03180736. Available at: https://clinicaltrials.gov/ct2/show/NCT03180736 Last accessed November 2017.
12. ClincalTrials.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 November 2017.
13. ClinicalTrials.gov. A study of subcutaneous versus (vs.) intravenous administration of dara­tu­mu­mab in participants with relapsed or refractory multiple myeloma. NCT03277105. Available at: https://clinicaltrials.gov/ct2/show/NCT03277105 Last accessed November 2017.
14. ClinicalTrials.gov. A study of daratumumab in combination with atezolizumab compared with atezolizu­mab alone in participants with previously treated advanced or metastatic non-small cell lung cancer (DARZALEX). NCT03023423. Available at: https://clinicaltrials.gov/ct2/show/NCT03023423 Last accessed November 2017.
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 November 2017.
16. ClinicalTrials.gov. A study to assess the clinical efficacy and safety of daratumumab in partici­pants with relapsed or refractory natural killer/T-cell lymphoma (NKTCL), nasal type. NCT02927925. Available at: https://clinicaltrials.gov/ct2/show/NCT02927925 Last accessed November 2017.
17. ClinicalTrials.gov. Study to separately evaluate the activity of talacotuzumab (JNJ-56022473) or dara­tumu­mab in transfusion-dependent participants with low or intermediate-1 risk myelodysplastic syndromes (MDS) who are relapsed or refractory to erythropoiesis-stimulating agent (ESA) treatment. NCT03011034. Available at: https://clinicaltrials.gov/ct2/show/NCT03011034 Last accessed November 2017.
18. Johnson&Johnson. Johnson & Johnson Reports 2017 Third-Quarter Results: Available at: http://files.shareholder.com/downloads/JNJ/5503318818x0x959926/4F369F4B-E11C-42B8-9D04-8CEA2EDF2DD9/JNJ_News_2017_10_17_News_Releases.pdf Last accessed November 2017.
19. ClinicalTrials.gov. A study of subcutaneous daratumumab versus active monitoring in participants with high-risk smoldering multiple myeloma. NCT03301220. Available at: https://clinicaltrials.gov/ct2/show/NCT03301220 Last accessed November 2017.
20. ClinicalTrials.gov. A study to test the safety and effectiveness of nivolumab combined with dara­tu­mumab in patients with pancreatic, non-small cell lung or triple negative breast cancers, that have advanced or have spread. NCT03098550. Available at: https://clinicaltrials.gov/ct2/show/NCT03098550 Last accessed November 2017.
21. ClinicalTrials.gov. A study to evaluate the efficacy and safety of daratumumab in combi­na­tion with cyclo­phos­phamide, bortezomib and dexamethasone (CyBorD) compared to CyBorD alone in newly diagnosed systemic amyloid light-chain (AL) amyloidosis. NCT03201965. Available at: https://clinicaltrials.gov/ct2/show/NCT03201965 Last accessed November 2017.
22. American Society of Clinical Oncology. Multiple myeloma: overview. Available at: http://www.cancer.net/cancer-types/multiple-myeloma/overview Last accessed November 2017.
23. GLOBOCAN 2012. Multiple myeloma. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=62968&Textp=Europe&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=13&type=0&window=1&submit=%C2%A0Execute Last accessed November 2017.
24. American Cancer Society. Multiple myeloma: causes, risk factors and prevention. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8739.00.pdf Last accessed November 2017.
25. 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.
26. Costa LJ, Gonsalves WI, Kumar SK. Early mortality in multiple myeloma. Leukemia. 2015;29:1616-8.
27. 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.
28. 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 November 2017.
29. 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.