BEERSE, Belgium--(BUSINESS WIRE)--Sep 3, 2018--The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the European Commission (EC) has granted marketing authorisation for Darzalex ®  (daratumumab) for use as frontline (initial) therapy. The approval is for the use of daratumumab in combination with bortezomib, melphalan and prednisone (VMP), for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).

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Dr Catherine Taylor, Europe, Middle East and Africa (EMEA) Haematology Therapeutic Area Lead, Janssen (Photo: Business Wire)

The approval is based on results from the randomised, open-label, multicentre Phase 3 ALCYONE (MMY3007) study, published in the  earlier this year. 1  Daratumumab in combination with VMP reduced the risk of disease progression or death by 50 percent, compared to treatment with VMP alone (Hazard Ratio [HR] = 0.50; 95 percent CI [0.38-0.65], p<0.001). 1  The median progression free survival (PFS) for daratumumab-VMP had not yet been reached, compared to an estimated median PFS of 18.1 months for patients who received VMP alone. 1

“Today’s approval is extremely important for multiple myeloma patients, as providing a frontline treatment option that demonstrates a deep and durable response often provides the best chance at lasting remission. It’s all the more remarkable considering it has only been ten years since the first dose of daratumumab was administered in the earliest human studies,” said Dr Torben Plesner, MD, the first investigator to administer daratumumab in human trials and Professor, Head of the Department of Hematology at Vejle Hospital, Denmark. “I am proud that patients across Europe now have the option to use a monoclonal antibody as an initial therapy.”

“We are incredibly grateful to the patients and physicians who participated in the clinical programme for making this approval possible,” said Dr Catherine Taylor, Europe, Middle East and Africa (EMEA) Haematology Therapeutic Area Lead, Janssen. “Our mission has been to ensure daratumumab reaches as many eligible patients as possible and to prolong and improve their quality of life. This is a significant step forward.”

The most common (≥10 percent) Grade 3/4 treatment emergent adverse events (TEAEs) (daratumumab-VMP vs. VMP) were neutropenia (40 percent vs. 39 percent), thrombocytopenia (34 percent vs. 38 percent), anaemia (16 percent vs. 20 percent) and pneumonia (11 percent vs. 4 percent). 1  One patient in each arm discontinued treatment due to pneumonia and 0.9 percent of patients discontinued daratumumab due to an infection. 1  Twenty-eight percent of patients experienced infusion-related reactions (IRRs) due to daratumumab, and most IRRs occurred during the first infusion. 1  In the daratumumab-VMP arm, 42 percent of patients experienced a serious adverse event (SAE), compared to 33 percent in the VMP arm. The most common (≥2 percent) SAE (daratumumab-VMP vs. VMP) was pneumonia (10 percent vs. 3 percent). 1  Additional information about this study can be found at  www.ClinicalTrials.gov  (NCT02195479). 2

In Europe, daratumumab is also 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; 3  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. 3

#ENDS#

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. 4-6  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. 3  A subset of myeloid derived suppressor cells (MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were decreased by daratumumab. 3  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. 2,7-14  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. 15-20  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. 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  MM is the second most common form of blood cancer, with around 40,570 new cases in Europe in 2015. 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 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   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.

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References

1. 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.

2. 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 July 2018.

3. 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 July 2018.

4. 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.

5. 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.

6. 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.

7. 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 July 2018.

8. 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 July 2018.

9. 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 July 2018.

10. 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 July 2018.

11. 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 July 2018.

12. 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 July 2018.

13. 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 July 2018.

14. 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 July 2018.

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 July 2018.

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 July 2018.

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 July 2018.

18. 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 July 2018.

19. 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 July 2018.

20. 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 July 2018.

21. 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 July 2018.

22. American Society of Clinical Oncology. Multiple myeloma: introduction. Available at:  https://www.cancer.net/cancer-types/multiple-myeloma/introduction  Last accessed July 2018.

23. 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 July 2018.

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 July 2018.

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 July 2018.

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.

PHEM/DAR/0718/0005

AUGUST 2018

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