Janssen’s first-in-class CD38-directed mono­clonal anti­body now rec­om­mended for approval earlier in the treat­ment path­way in com­bi­na­tion with two standard of care regi­mens

Beerse, Belgium (Press Release) – Janssen-Cilag Inter­na­tional NV 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).¹ If approved by the European Com­mis­sion, dara­tu­mu­mab can be used in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone; or bor­tez­o­mib and dexa­meth­a­sone, for the treat­ment of adult patients with multiple myeloma (MM) who have received at least one prior ther­apy.¹

Despite the incredible work of the on­col­ogy com­munity over the past decade, MM remains an incurable blood cancer that occurs when malignant plasma cells grow un­con­trol­lably in the bone marrow.²

The Positive Opinion of the CHMP was based on a review of data from the Phase 3 MMY3003 (POLLUX) study, published in The New England Journal of Medicine in October 2016,³ and the Phase 3 MMY3004 (CASTOR) study, also published in The New England Journal of Medicine in August 2016.⁴

The safety profile of dara­tu­mu­mab in com­bi­na­tion with standard-of-care regi­mens was con­sis­tent with mono­therapy studies. In com­bi­na­tion with lena­lido­mide, and dexa­meth­a­sone (POLLUX) the most common ad­verse events of grade 3 or 4 during treat­ment were neu­tro­penia (51.9%), thrombo­cytopenia (12.7%), and anaemia (12.4%).³ Dara­tu­mu­mab-associated in­fusion-related reac­tions occurred in 47.7% of the patients and were mostly of grade 1 or 2.³ In com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone (CASTOR) three of the most common grade 3 or 4 adverse events reported were thrombo­cytopenia (45.3%), anaemia (14.4%), and neu­tro­penia (12.8%).⁴ Infusion-related reac­tions that were asso­ci­ated with dara­tu­mu­mab treat­ment were reported in 45.3% of the patients; these reac­tions were mostly grade 1 or 2 (grade 3 in 8.6% of patients), and in 98.2% of these patients, they occurred during the first in­fusion.⁴

“This Positive Opinion recognises progress in the treat­ment of multiple myeloma and has the poten­tial to offer new treat­ment options to eli­gible patients.” said Torben Plesner, M.D., Vejle Hospital, Vejle, Denmark, a dara­tu­mu­mab clin­i­cal trial investigator. “Daratumumab has already dem­onstrated single-agent efficacy in highly refractory patients. Now, con­sis­tent with these data, the results when used in com­bi­na­tion with standard-of-care regi­mens after one prior line of ther­apy are also en­cour­ag­ing.”

Daratumumab first received con­di­tional approval from the European Com­mis­sion (EC) in May 2016, indi­cated 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.^5,6 Dara­tu­mu­mab was the first CD38-directed mono­clonal anti­body approved for use world­wide.

“Almost all patients with multiple myeloma have to endure relapses which typically be­come more aggres­sive,” said Dr Catherine Taylor, Haematology Therapeutic Area Lead, Janssen Europe, the Middle East and Africa (EMEA). “I am heartened by this im­por­tant and rapid recom­men­da­tion which recognises the progress in multiple myeloma treat­ment.”

The CHMP’s Positive Opinion will now be reviewed by the European Com­mis­sion, which has the authority to grant approval of the new indi­ca­tion.

This mile­stone follows last year’s de­ci­sion by the U.S. Food and Drug Admin­istra­tion (FDA) on 21 November 2016, to approve the expanded use of dara­tu­mu­mab in com­bi­na­tion with bor­tez­o­mib/dexamethasone or lena­lido­mide/dexamethasone in patients with multiple myeloma who have received at least 1 prior ther­apy.⁷

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.² MM is the second most common form of blood cancer, with around 39,000 new cases world­wide in 2012.⁸ MM most commonly affects people over the age of 65 and is more common in men than in women.⁹ 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.¹⁰ Almost 29% of patients with MM will die within one year of diag­nosis.¹¹ Although treat­ment may result in remission, unfortunately, patients will most likely relapse as there is cur­rently no cure. 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.⁹ Patients who relapse after treat­ment with standard ther­a­pies, in­­clud­ing PIs and immuno­modu­la­tory agents, have poor prognoses and few treat­ment options avail­able.¹²

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.^13-15 Dara­tu­mu­mab induces rapid tumour cell death through apop­tosis (programmed cell death)^6,16 and multiple immune-mediated mech­a­nisms of action, in­­clud­ing complement-dependent cyto­tox­icity (CDC), anti­body-dependent cellular cyto­tox­icity (ADCC) and anti­body-dependent cellular phago­cytosis (ADCP).^6,17,18 Dara­tu­mu­mab has also dem­onstrated immuno­modulatory effects that con­trib­ute to tumour cell death via a de­crease in immune sup­pres­sive cells in­­clud­ing T-regs, B-regs and myeloid-derived sup­pressor cells.^6,19 Dara­tu­mu­mab is being eval­u­ated in a compre­hensive clin­i­cal devel­op­ment pro­gramme that in­cludes five Phase 3 studies across a range of treat­ment settings in multiple myeloma. Additional studies are ongoing or planned to assess its poten­tial in other malignant and pre-malignant diseases in which CD38 is ex­pressed. 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/ema/index.jsp?curl=pages/medicines/human/medicines/004077/human_med_001979.jsp&mid=WC0b01ac058001d124.

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 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.

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 benefits of, and expanded indi­ca­tion for, DARZALEX® (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, any of the other Janssen Pharma­ceu­tical Com­panies and/or Johnson & Johnson. Risks and un­cer­tain­ties in­clude, but are not limited to: the un­cer­tain­ties in­her­ent in prod­uct 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 or financial distress 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 description 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 3, 2016, in­­clud­ing in Exhibit 99 thereto, 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

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Source: Janssen.