First-in-class CD38-directed mono­clonal anti­body now approved for use in com­bi­na­tion with two standard of care regi­mens

Beerse, Belgium (Press Release) – Janssen-Cilag Inter­na­tional NV (“Janssen”) today announced that the European Com­mis­sion (EC) has granted approval to DARZALEX®▼ (dara­tu­mu­mab) for use in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, or bor­tez­o­mib (VELCADE®) and dexa­meth­a­sone, for the treat­ment of adult patients with multiple myeloma (MM) who have received at least one prior ther­apy.

The EC’s de­ci­sion was based on data from the Phase 3 POLLUX (MMY3003) study, presented in the plenary session at ASCO 2016 and published in the New England Journal of Medicine, in August 2016¹; and Phase 3 CASTOR (MMY3004) study, presented in the Pres­i­dential session at EHA 2016 and also published in the New England Journal of Medicine in October 2016.² The addi­tion of dara­tu­mu­mab sig­nif­i­cantly reduced the risk of disease pro­gres­sion or death, by 63% in POLLUX and 61% in CASTOR, when com­bined with standard of care regi­mens (p<0.001 in both studies).^1,2

The safety profile of dara­tu­mu­mab in com­bi­na­tion with standard of care regi­mens was con­sis­tent with dara­tu­mu­mab mono­therapy studies and with that for the standard of care regi­mens. 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%).¹ Dara­tu­mu­mab-associated in­fusion-related reac­tions occurred in 47.7% of the patients and were mostly of grade 1 or 2.¹ 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%).² 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.²

“Data from both the CASTOR and POLLUX studies dem­onstrated im­proved pro­gres­sion-free survival and a reduction in disease pro­gres­sion or death com­pared to standard of care,” said Torben Plesner, M.D., Vejle Hospital, Vejle, Denmark, a dara­tu­mu­mab clin­i­cal trial investigator. “Together, these results show dara­tumu­mab in com­bi­na­tion with either a pro­te­a­some inhibitor or an immuno­modu­latory agent has the poten­tial to provide clin­i­cal benefit to patients after one or more lines of ther­apy.”

“This approval is an im­por­tant step for people living with multiple myeloma across our region and offers some patients a new treat­ment option. We are en­cour­aged by the data we have seen for dara­tu­mu­mab to date and will con­tinue to in­ves­ti­gate its poten­tial,” said Dr Catherine Taylor, Haematology Therapeutic Area Lead, Janssen Europe, Middle East and Africa (EMEA).

The initial Marketing Authorisation was granted in May 2016 for dara­tu­mu­mab as mono­therapy for the treat­ment of adult patients with re­lapsed and refractory multiple myeloma, whose prior ther­apy in­cluded a pro­te­a­some inhibitor and an immuno­modu­latory agent and who have dem­onstrated disease pro­gres­sion on the last ther­apy.³ This Authorisation was marked as con­di­tional based on Janssen providing addi­tional data from the MMY3003 (POLLUX) and MMY3004 (CASTOR) studies.⁴ With the provision of these results, the EC has con­sidered the Specific Obligations asso­ci­ated with the con­di­tional Marketing Authorisation to have been fulfilled, allow­ing the switch from con­di­tional to full approval.⁵

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.⁶ MM is the second most common form of blood cancer, with around 39,000 new cases world­wide in 2012.⁷ MM most commonly affects people over the age of 65 and is more common in men than in women.⁸ 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.⁹ Almost 29% of patients with MM will die within one year of diag­nosis.¹⁰ 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.⁸ Patients who relapse after treat­ment with standard ther­a­pies, in­­clud­ing PIs and immuno­modu­la­tory agents, have poor prognoses and few treat­ment options avail­able.¹¹

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.^12-14 Dara­tu­mu­mab induces rapid tumour cell death through apop­tosis (pro­grammed cell death)^4,15 and multiple immune-mediated mech­a­nisms of action, in­­clud­ing complement-dependent cyto­toxicity (CDC), anti­body-dependent cellular cyto­tox­icity (ADCC) and anti­body-dependent cellular phago­cytosis (ADCP).^4,16,17 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.^4,18 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=WC0b01ac058001d124.⁵

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 poten­tial benefits and treat­ment options related to 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 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 behavior 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 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 in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” 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.