• New sub­cu­tane­ous, fixed-dose for­mu­la­tion of dara­tu­mu­mab reduces treat­ment time from hours to min­utes, with com­parable ef­fi­cacy and fewer in­fusion-related reac­tions^1,2
• Daratumumab is now the only approved sub­cu­tane­ous CD38-directed anti­body for the treat­ment of these mul­ti­ple myeloma in­di­ca­tions in Europe

Beerse, Belgium (Press Release) – The Janssen Pharma­ceu­tical Com­panies of John­son & John­son an­nounced to­day that the Euro­pean Com­mis­sion (EC) has granted mar­ket­ing authori­sa­tion for DAR­ZA­LEX®▼ (dara­tu­mu­mab) sub­cu­tane­ous (SC) for­mu­la­tion for the treat­ment of adult patients with mul­ti­ple myeloma (MM). Dara­tu­mu­mab SC is admin­istered as a fixed dose, which sig­nif­i­cantly reduces treat­ment time, from hours to approx­i­mately three to five min­utes, when com­pared to dara­tu­mu­mab in­tra­venous (IV) for­mu­la­tion.¹ In addi­tion, only the first dose of dara­tu­mu­mab SC needs to be admin­istered in an en­viron­ment where resuscitation facilities are avail­able. The ap­prov­al applies to all cur­rent dara­tu­mu­mab in­di­ca­tions in front­line and re­lapsed / re­frac­tory settings, and patients cur­rently on dara­tu­mu­mab IV can switch to the SC for­mu­la­tion should they choose to.

Data sup­port­ing the ap­prov­al show that dara­tu­mu­mab SC dem­onstrated a con­sis­tent over­all re­sponse rate (ORR) and a similar safety profile com­pared with dara­tu­mu­mab IV in patients with re­lapsed or re­frac­tory MM.¹ In addi­tion, there was a nearly two-thirds re­duc­tion in sys­temic in­fusion-related reac­tions (IRRs) for dara­tu­mu­mab SC com­pared to dara­tu­mu­mab IV (13 per­cent vs. 35 per­cent, re­spec­tively).¹ The novel SC for­mu­la­tion of dara­tu­mu­mab is co-formulated with recombinant human hyal­uron­i­dase PH20 (rHuPH20) [Halozyme's ENHANZE® drug de­livery tech­nology].

“Multiple myeloma is an incurable blood can­cer that is often asso­ci­ated with time-intensive treat­ment regi­mens, which can be burdensome for patients and physicians. Today’s ap­prov­al marks im­por­tant progress for the on­col­ogy com­munity as it means dara­tu­mu­mab can now be admin­istered in sig­nif­i­cantly less time, thereby reducing the time patients need to be in the clin­i­cal setting,” 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. “Given the cur­rent health climate, this is timely and welcome news, par­tic­u­larly for immunocompromised patients.”

“This new for­mu­la­tion was spe­cif­i­cally de­signed as the next step in enhancing the treat­ment ex­peri­ence with dara­tu­mu­mab, without compromising on safety or ef­fi­cacy,” said Patrick Laroche, M.D., Hae­ma­tol­ogy Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. “Since its first launch, dara­tu­mu­mab has been used by more than 130,000 patients globally, and Janssen is pleased to ex­pand our offering by making the sub­cu­tane­ous for­mu­la­tion avail­able for all pre­vi­ously approved in­di­ca­tions.”

The ap­prov­al is sup­ported by data from the Phase 2 PLEIADES (MMY2040) and Phase 3 COLUMBA (MMY3012) stud­ies.

In the PLEIADES study, which eval­u­ated the ef­fi­cacy and safety of dara­tu­mu­mab SC in com­bi­na­tion ther­a­pies, objective re­sponses were dem­onstrated in com­bi­na­tion with bor­tez­o­mib, mel­phalan, and pred­ni­sone (D-VMP) in newly diag­nosed trans­plant in­eli­gible patients.² In addi­tion, objective re­sponses were dem­onstrated in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (D-Rd) in re­lapsed or re­frac­tory patients who re­ceived one prior line of ther­apy.²

In the COLUMBA study, at a median follow-up of 7.5 months, the ORR was 41 per­cent for patients taking dara­tu­mu­mab SC as a mono­therapy, com­pared to 37 per­cent for those taking dara­tu­mu­mab IV as a mono­therapy (95 per­cent con­fi­dence in­ter­val [CI], 1.11 (0.89-1.37); P<0.0001).³ The ORR was similar across all clin­i­cally relevant subgroups, in­clud­ing bodyweight.¹ The ratio of geometric means of C_trough for dara­tu­mu­mab SC over dara­tu­mu­mab IV was 108 per­cent (90 per­cent CI, 96 per­cent-122 per­cent).¹ The pro­gres­sion-free sur­vival was com­parable be­tween the dara­tu­mu­mab SC and dara­tu­mu­mab IV (Hazard Ratio [HR] = 0.99; 95 per­cent CI, 0.78-1.26; P<0.9258).¹ The median duration for each SC in­jec­tion was five min­utes, com­pared to more than three hours with IV in­fusions.¹

The most common (>5 per­cent) Grade 3/4 treat­ment-emergent ad­verse events (TEAEs) were thrombo­cyto­penia (14 per­cent vs. 14 per­cent), anaemia (13 per­cent vs. 14 per­cent) and neu­tro­penia (13 per­cent vs. 8 per­cent).³ A lower rate of IRRs was ob­served in the arm that re­ceived dara­tu­mu­mab SC com­pared to dara­tu­mu­mab IV (13 per­cent vs. 35 per­cent, re­spec­tively) (Odds Ratio = 0.28; 95 per­cent CI (0.18-0.44); P<0.0001).³ The pri­mary reasons for treat­ment dis­con­tinu­a­tion in­cluded progressive dis­ease (43 per­cent in the SC arm vs. 44 per­cent in the IV arm) and ad­verse events (7 per­cent in the SC arm vs. 8 per­cent in the IV arm).¹

“Today’s ap­prov­al highlights Janssen’s com­mitment to gaining a better under­stand­ing of the evolving needs of people living with mul­ti­ple myeloma, and to the de­vel­op­ment of new inno­va­tions, com­bi­na­tions, and for­mu­la­tions to best meet those needs,” adds Craig Tendler, M.D., Vice Pres­i­dent, Clinical De­vel­op­ment and Global Medical Affairs, Oncology at Janssen Re­search & De­vel­op­ment, LLC.

Outside of Europe, Janssen recently re­ceived ap­prov­al from the U.S. Food and Drug Admin­istra­tion for the SC for­mu­la­tion of DAR­ZA­LEX – known locally as DAR­ZA­LEX FASPRO™ (dara­tu­mu­mab and hyal­uron­i­dase-fihj) – for the treat­ment of patients with MM.⁴

In Europe, dara­tu­mu­mab is in­di­cated:⁵

• 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)^6,7

The ran­domised, open-label, multicentre Phase 3 study in­cluded 522 patients with mul­ti­ple myeloma (MM) 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 dara­tu­mu­mab sub­cu­tane­ous for­mu­la­tion (SC; n=263), patients (median age of 65) re­ceived a fixed dose of dara­tu­mu­mab 1,800 milligrams (mg) co-formulated with recombinant human hyal­uron­i­dase (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 arm that re­ceived dara­tu­mu­mab in­tra­venous for­mu­la­tion (IV; n=259), patients (median age of 67) re­ceived 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 per­cent] of the 95 per­cent con­fi­dence in­ter­val [CI] of the SIRIUS trial, with rel­a­tive risk [RR] analysed by Farrington-Manning test) and pre-dose cycle 3, day 1 (C3D1) dara­tu­mu­mab C_trough (non-inferiority = lower bound of 90 per­cent CI for the ratio of the geometric means [GM] ≥80 per­cent).

About the PLEIADES Study (MMY2040)⁸

The non-randomised, open-label, parallel assignment Phase 2 PLEIADES trial in­cluded 240 adults either newly diag­nosed or with re­lapsed or re­frac­tory mul­ti­ple myeloma (MM). Patients with newly diag­nosed MM were treated with 1,800 mg of dara­tu­mu­mab sub­cu­tane­ous for­mu­la­tion (SC) 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 dara­tu­mu­mab SC plus lena­lido­mide and dexa­meth­a­sone (D-Rd). The pri­mary end­point for the D-VMP and D-Rd cohorts was over­all re­sponse rate (ORR). 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 MM treated with dara­tu­mu­mab SC plus car­filz­o­mib and dexa­meth­a­sone was sub­se­quently added to the study.

About dara­tu­mu­mab

Daratumumab is a first-in-class⁹ bio­logic targeting CD38, a surface pro­tein that is highly ex­pressed across mul­ti­ple myeloma (MM) cells, re­gard­less of dis­ease stage.¹⁰ 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.5 A subset of myeloid derived sup­pressor cells (CD38+ MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) are de­creased by dara­tu­mu­mab-mediated cell lysis.⁵ Since launch, it is esti­mated that 130,000 patients have been treated with dara­tu­mu­mab world­wide.¹¹ Dara­tu­mu­mab is being eval­u­ated in a com­pre­hen­sive clin­i­cal de­vel­op­ment pro­gramme across a range of treat­ment settings in MM, such as in front­line and re­lapsed settings.^{12,13,14,15,16,17,18,19} 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.20,21 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/documents/product-information/darzalex-epar-product-information_en.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.²²

About Multiple Myeloma (MM)

Multiple myeloma (MM) is an incurable blood can­cer that starts in the bone mar­row and is char­ac­ter­ised by an excessive pro­lif­er­a­tion of plasma cells.²³ In Europe, more than 48,200 people were diag­nosed with MM in 2018, and more than 30,800 patients died.²⁴ Around 50 per­cent of newly diag­nosed patients do not reach five-year sur­vival,^25,26 and almost 29 per­cent of patients with mul­ti­ple myeloma will die within one year of diag­nosis.²⁷

Although treat­ment may re­­sult in remission, unfortunately, patients will most likely relapse as there is cur­rently no cure.28 Re­lapsed and re­frac­tory myeloma is defined as dis­ease that is nonresponsive while on salvage ther­apy, or progresses within 60 days of last ther­apy in patients who have achieved minimal re­sponse (MR) or better at some point pre­vi­ously be­fore then pro­gress­ing in their dis­ease course.²⁹ While some patients with MM have no symp­toms at all, others are diag­nosed due to symp­toms that can in­clude bone prob­lems, low blood counts, cal­cium elevation, kidney prob­lems or in­fec­tions.³⁰ Patients who relapse after treat­ment with stan­dard ther­a­pies, in­clud­ing pro­te­a­some in­hib­i­tors and immuno­modu­la­tory agents, have poor prognoses and re­quire new ther­a­pies for con­tinued dis­ease con­trol.³¹

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.