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) for use as frontline (initial) ther­apy.¹ The recom­men­da­tion is for the use of 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 (ASCT).¹

“Multiple myeloma be­comes harder to treat each time it returns, so the goal of initial ther­apy is to prevent the cancer from progressing for as long as possible,” said Dr Maria-Victoria Mateos, Ph.D., lead ALCYONE study investigator and Director of the Myeloma Unit at University Hospital of Salamanca-IBSAL Salamanca, Spain. “Selecting the right treat­ment regi­men for newly diag­nosed patients is critical to their long-term survival, especially those who are trans­plant in­eli­gible, so dara­tu­mu­mab could offer an im­por­tant new standard of care in this indi­ca­tion.”

The CHMP’s recom­men­da­tion is based on results from the ran­domised, open-label, multicentre Phase 3 ALCYONE (MMY3007) study, recently published in the New England Journal of Medicine.² Additional in­­for­ma­tion about this study can be found at www.ClinicalTrials.gov (NCT02195479).³

“Clinical findings have con­sis­tently dem­onstrated the compelling benefit dara­tu­mu­mab offers across all lines of ther­apy in multiple myeloma, and this pos­i­tive recom­men­da­tion brings us one step closer to providing this ground-breaking option to more patients in Europe,” said Dr Catherine Taylor, Europe, Middle East and Africa (EMEA) Haematology Therapeutic Area Lead, Janssen. “Through our research and devel­op­ment efforts, we remain committed to identifying and treating patients earlier and earlier in their cancer journey, when they are healthier and have the best chance at lasting remission.”

In Europe, 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;⁴ and 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.⁴

A final de­ci­sion re­gard­ing the approval of dara­tu­mu­mab for newly diag­nosed patients is ex­pec­ted from the European Com­mis­sion in the coming months.

In the U.S.A., dara­tu­mu­mab in the frontline setting was granted Priority Review by the U.S. Food and Drug Admin­istra­tion (FDA) in January this year,⁵ and was recently approved for use in this indi­ca­tion.⁶

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.^7-9 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 (MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) were de­creased by dara­tu­mu­mab.⁴ Dara­tumu­mab is being eval­u­ated in a com­pre­hen­sive clin­i­cal devel­op­ment pro­gramme that in­cludes nine Phase 3 studies across a range of treat­ment settings in multiple myeloma, such as in frontline and re­lapsed settings.^3,10-17 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.^18-23 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 licence to develop, manu­fac­ture and commercialise dara­tu­mu­mab.²⁴

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.²⁵ MM is the second most common form of blood cancer, with around 40,570 new cases in Europe in 2015.26 MM most commonly affects people over the age of 65 and is more common in men than in women.²⁷ 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.²⁸ Almost 29% of patients with MM will die within one year of diag­nosis.²⁹

Although treat­ment may result in remission, unfortunately, patients will most likely relapse as there is cur­rently no cure.³⁰ 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.³¹ Patients who relapse after treat­ment with standard ther­a­pies, in­­clud­ing PIs and immuno­modu­la­tory agents, have poor prognoses and few treat­ment options avail­able.³²

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 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, 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 31, 2017, in­­clud­ing in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the com­pany’s sub­se­quent Quarterly Reports on Form 10-Q and other 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

1. EMA. Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 23-26 July 2018. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2018/07/news_detail_002994.jsp&mid=WC0b01ac058004d5c1 Last accessed July 2018.
2. Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus bor­tez­o­mib, mel­phalan and pred­ni­sone for untreated myeloma. N Engl J Med. 2018;378:518-528.
3. 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 June 2018.
4. European Medicines Agency. DARZALEX summary of prod­uct char­ac­ter­istics, June 2018. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004077/WC500207296.pdf Last accessed June 2018.
5. U.S. Food and Drug Admin­istra­tion. Priority review. Available at: https://www.fda.gov/forpatients/approvals/fast/ucm405405.htm Last accessed June 2018.
6. U.S. Food and Drug Admin­istra­tion. DARZALEX Prescribing Information, May 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761036s013lbl.pdf Last accessed June 2018.
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. 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.
9. 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.
10. 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 June 2018.
11. 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 June 2018.
12. 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 June 2018.
13. 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 June 2018.
14. 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 June 2018.
15. 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 June 2018.
16. 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 June 2018.
17. 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 June 2018.
18. 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 June 2018.
19. 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 June 2018.
20. 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 June 2018.
21. 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 June 2018.
22. 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 June 2018.
23. 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 June 2018.
24. Johnson & Johnson. Janssen Biotech announces global license and devel­op­ment agreement for inves­ti­ga­tional anti-cancer agent dara­tu­mu­mab. Press release August 20, 2012. Available at: http://www.investor.jnj.com/releaseDetail.cfm?releaseid=703517 Last accessed June 2018.
25. American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction Last accessed June 2018.
26. GLOBOCAN 2012. Multiple myeloma. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=62968&Text-p=Europe&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=0&window=1&submit=%C2%A0Execute%C2%A0 Last accessed June 2018.
27. 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 June 2018.
28. 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.
29. Costa LJ, Gonsalves WI, Kumar SK. Early mortality in multiple myeloma. Leukemia. 2015;29:1616-8.
30. 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.
31. 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 June 2018.
32. 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 Pharma­ceu­ticals.