• New sub­cu­tane­ous for­mu­la­tion reduces the time taken for patients to re­ceive dara­tu­mu­mab treat­ment from hours to approx­i­mately three to five min­utes, with similar ef­fi­cacy and fewer in­fusion-related reac­tions com­pared to in­tra­venous admin­istra­tion^1,2
• If approved, dara­tu­mu­mab sub­cu­tane­ous for­mu­la­tion will be the first mono­clonal anti­body approved in Europe for sub­cu­tane­ous admin­istra­tion for patients with mul­ti­ple myeloma
• Positive Opinion is based on data from the Phase 3 COLUMBA (MMY3012) and Phase 2 PLEIADES (MMY2040) stud­ies

Beerse, Belgium (Press Release) – The Janssen Pharma­ceu­tical Com­panies of John­son & John­son an­nounced to­day that the Com­mit­tee for Medicinal Products for Human Use (CHMP) of the Euro­pean Medicines Agency (EMA) has issued a Positive Opinion rec­om­mending ap­­prov­al for DAR­ZA­LEX®▼ (dara­tu­mu­mab) sub­cu­tane­ous (SC) for­mu­la­tion for the treat­ment of adult patients with mul­ti­ple myeloma in front­line and re­lapsed / re­frac­tory settings. The novel SC for­mu­la­tion of dara­tu­mu­mab is co-formulated with recombinant human hyal­uron­i­dase PH20 (rHuPH20) [Halozyme's ENHANZE® drug de­livery tech­nology] and reduces treat­ment time from hours to approx­i­mately three to five min­utes, with similar ef­fi­cacy, and fewer in­fusion-related reac­tions com­pared to in­tra­venous (IV) admin­istra­tion.^1,2 The CHMP’s Positive Opinion for dara­tu­mu­mab SC for­mu­la­tion applies to all cur­rent dara­tu­mu­mab in­di­ca­tions in­clud­ing newly diag­nosed and trans­plant-ineligible patients, as well as re­lapsed or re­frac­tory patients.

“Despite thera­peutic ad­vances in the treat­ment of mul­ti­ple myeloma, the time taken for admin­istra­tion of most in­tra­venous treat­ments is rel­a­tive­ly long and there have been few sig­nif­i­cant im­prove­ments over the years,” said Maria-Victoria Mateos, M.D., Ph.D., COLUMBA pri­mary in­ves­ti­ga­tor and Director of the Myeloma Unit at Uni­ver­sity Hospital of Salamanca-IBSAL, Salamanca, Spain. “The dara­tu­mu­mab sub­cu­tane­ous for­mu­la­tion has the poten­tial to trans­form the treat­ment ex­peri­ence for patients and physicians as it reduces time in the chair from hours to min­utes, and, because it is admin­istered as a fixed dose from the first treat­ment, it reduces preparation time and chances of error by elim­i­nat­ing the need for dose calculations.”

The Positive Opinion is sup­ported by data from the Phase 3 COLUMBA (MMY3012) and Phase 2 PLEIADES (MMY2040) stud­ies pre­sented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting and 62nd American Society of Hema­tol­ogy (ASH) Annual Meeting, re­spec­tive­ly.^1,2 The COLUMBA pre­sen­ta­tion in­cluded a non-inferiority comparison of dara­tu­mu­mab SC for­mu­la­tion to dara­tu­mu­mab IV for­mu­la­tion for co-primary end­points of over­all re­sponse rate and max­i­mum Ctrough con­cen­tra­tion.¹ Fur­ther­more, in a sub­se­quent paper pub­lished in The Lancet Hae­ma­tol­ogy, patient-reported treat­ment satisfaction scores with dara­tu­mu­mab SC versus dara­tu­mu­mab IV were re­ported using the modified-Cancer Therapy Satisfaction Questionnaire.³ The PLEIADES study eval­u­ated the dara­tu­mu­mab SC for­mu­la­tion in dif­fer­en­t com­bi­na­tion regi­mens in patients with newly diag­nosed mul­ti­ple myeloma or with re­lapsed / re­frac­tory dis­ease.²

“The sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab showed similar ef­fi­cacy and fewer in­fusion-related reac­tions com­pared to in­tra­venous dara­tu­mu­mab, and, over­all, patients ex­pressed satisfaction with sub­cu­tane­ous ther­apy. If approved, we are hopeful this new for­mu­la­tion could offer im­proved quality of life for patients with mul­ti­ple myeloma,” said Patrick Laroche, M.D., Hae­ma­tol­ogy Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. “Janssen is proud to have devel­oped a new for­mu­la­tion to meet the needs of our patients and con­tinue to make a meaningful dif­fer­ence to the lives of those living with mul­ti­ple myeloma.”

“Since its first Euro­pean ap­­prov­al in 2016, in­tra­venous dara­tu­mu­mab has been used in the treat­ment of more than 100,000 patients world­wide and, if approved, both new and existing patients with mul­ti­ple myeloma will be able to start or switch to the sub­cu­tane­ous for­mu­la­tion as part of their mul­ti­ple myeloma dara­tu­mu­mab-based treat­ment regi­mens,” adds Craig Tendler, M.D., Vice Pres­i­dent, Clinical De­vel­op­ment and Global Medical Affairs, Oncology at Janssen Re­search & De­vel­op­ment, LLC. “Today’s Positive Opinion rep­re­sents Janssen’s com­mitment to continuing to im­prove the treat­ment ex­peri­ence for patients living with mul­ti­ple myeloma.”

In Europe, dara­tu­mu­mab is in­di­cated:⁴

• in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone or with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of adult patients with newly diag­nosed multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant
• in com­bi­na­tion with bor­tez­o­mib, thalido­mide and dexa­meth­a­sone for the treat­ment of adult patients with newly diag­nosed multiple myeloma who are eli­gible for au­tol­o­gous stem cell trans­plant
• 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
• 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

About the COLUMBA Study (MMY3012)^3,5

The ran­domised, open-label, multicentre Phase 3 study in­cluded 522 patients with mul­ti­ple myeloma who had re­ceived at least three prior lines of ther­apy in­clud­ing a pro­te­a­some in­hib­i­tor (PI) and an immuno­modu­la­tory drug (IMiD), or whose dis­ease was re­frac­tory to both a PI and an IMiD. In the arm that re­ceived the sub­cu­tane­ously (SC) admin­istered for­mu­la­tion of dara­tu­mu­mab (n=263), patients (median age of 65) re­ceived a fixed dose of dara­tu­mu­mab 1,800 milligrams (mg) co-formulated with recombinant human hyal­uron­i­dase PH20 (rHuPH20) 2,000 Units per millilitre (U/mL), SC weekly for cycles 1 – 2, every two weeks for cycles 3 – 6, and every four weeks for cycle 7 and there­after. In the dara­tu­mu­mab IV arm (n=259), patients (median age of 67) re­ceived dara­tu­mu­mab for in­tra­venous in­fusion 16 milligrams per kilo­gram (mg/kg) weekly for cycles 1 – 2, every two weeks for cycles 3 – 6, and every four weeks for cycle 7 and there­after. Each cycle was 28 days. Patients in both treat­ment arms con­tinued until dis­ease pro­gres­sion or un­ac­cept­able toxicity. Co-primary end­points were over­all re­sponse rate (ORR) (non-inferiority = 60 per­cent retention of the lower bound [20∙8%] of the 95% CI of the SIRIUS trial, with rel­a­tive­ risk [RR] analysed by Farrington-Manning test) and pre-dose cycle 3, day 1 (C3D1) dara­tu­mu­mab Ctrough (non-inferiority = lower bound of 90 per­cent con­fi­dence in­ter­val (CI) for the ratio of the geometric means [GM] ≥80%).

About the PLEIADES Study (MMY2040)⁶

The non-randomised, open-label, parallel assignment study Phase 2 PLEIADES trial in­cluded 240 adults either newly diag­nosed or with re­lapsed or re­frac­tory mul­ti­ple myeloma. Patients with newly diag­nosed mul­ti­ple myeloma were treated with 1,800 mg of the sub­cu­tane­ous for­mu­la­tion in com­bi­na­tion with either bor­tez­o­mib, lena­lido­mide and dexa­meth­a­sone (D-VRd) or bor­tez­o­mib, mel­phalan and pred­ni­sone (D-VMP). Patients with re­lapsed or re­frac­tory dis­ease were treated with 1,800 mg of the sub­cu­tane­ous for­mu­la­tion plus lena­lido­mide and dexa­meth­a­sone (D-Rd). The pri­mary end­point for the D-VMP and D-Rd cohorts was over­all re­sponse rate. The pri­mary end­point for the D-VRd cohort was very good partial re­sponse or better rate. An addi­tional cohort of patients with re­lapsed and re­frac­tory mul­ti­ple myeloma treated with dara­tu­mu­mab plus car­filz­o­mib and dexa­meth­a­sone was sub­se­quently added to the study.

About dara­tu­mu­mab

Daratumumab is a first-in-class⁷ bio­logic targeting CD38, a surface pro­tein that is highly ex­pressed across mul­ti­ple myeloma cells, re­gard­less of dis­ease stage.⁸ 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 (CD38+ MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) were de­creased by dara­tu­mu­mab.⁴ Since launch, it is esti­mated that 100,000 patients have been treated with dara­tu­mu­mab world­wide.⁹ Dara­tu­mu­mab is being eval­u­ated in a com­pre­hen­sive clin­i­cal de­vel­op­ment pro­gramme across a range of treat­ment settings in mul­ti­ple myeloma, such as in front­line and re­lapsed settings.^{10,11,12,13,14,15,16,17} Addi­tional stud­ies are on­go­ing or planned to assess its poten­tial in other malignant and pre-malignant haema­to­logic dis­eases in which CD38 is ex­pressed, such as smoul­der­ing myeloma.^18,19 For more in­for­ma­tion, please see https://www.clinicaltrials.gov/.

For fur­ther in­for­ma­tion on dara­tu­mu­mab, please see the Summary of Product Characteristics at https://www.ema.europa.eu/en/medicines/human/EPAR/darzalex.

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.²⁰

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.²¹ In Europe, more than 48,200 people were diag­nosed with MM in 2018, and more than 30,800 patients died.²² Almost 60 per­cent of patients with MM do not sur­vive more than five years after diag­nosis.²³

Although treat­ment may re­­sult in remission, unfortunately, patients will most likely relapse as there is cur­rent no cure.24 Re­frac­tory MM is when a patient’s dis­ease progresses within 60 days of their last ther­apy.^25,26 Re­lapsed can­cer is when the dis­ease has returned after a period of initial, partial or com­plete remission.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 pro­te­a­some in­hib­i­tors and immuno­modu­la­tory agents, have poor prognoses and few treat­ment op­tions avail­able.²⁹

About the Janssen Pharma­ceu­tical Com­panies of John­son & John­son

At Janssen, we’re creating a future where dis­ease is a thing of the past. We’re the Pharma­ceu­tical Com­panies of John­son & John­son, work­ing tirelessly to make that future a reality for patients every­where by fighting sickness with science, im­prov­ing access with ingenuity, and heal­ing hope­less­ness with heart. We focus on areas of med­i­cine where we can make the biggest dif­fer­ence: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com/emea. Follow us at www.twitter.com/janssenEMEA for our latest news. Janssen-Cilag, Janssen Re­search & De­vel­op­ment, LLC and Janssen Biotech, Inc. 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 the ben­e­fits of dara­tu­mu­mab for the treat­ment of patients with mul­ti­ple myeloma. 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 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 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 29, 2019, in­clud­ing in the sections cap­tioned “Cautionary Note Regarding Forward-Looking State­ments” and “Item 1A. Risk Factors,” and in the com­pany’s most recently filed Quar­ter­ly Report on Form 10-Q, 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 nor John­son & John­son under­takes to up­date any for­ward-looking state­ment as a re­­sult of new in­for­ma­tion or future events or de­vel­op­ments.

ENHANZE® is a registered trade­mark of Halozyme.

References

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2. Chari A, San-Miguel J, McCarthy H, et al. Subcutaneous dara­tu­mu­mab plus standard treat­ment regi­mens in patients with multiple myeloma across lines of ther­apy: Pleiades study update. Blood. 2019;134(Suppl.1):abstract 3152.
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Source: Janssen.