Beerse, Belgium (Press Release) – 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).

The approval is based on results from the ran­domised, open-label, multicentre Phase 3 ALCYONE (MMY3007) study, published in the New England Journal of Medicine 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

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 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.