• Subcutaneous fixed-dosed for­mu­la­tion of DAR­ZA­LEX® (dara­tu­mu­mab) approved in Europe for the treat­ment of adult patients with mul­ti­ple myeloma
• Approval follows pos­i­tive opinion by Euro­pean Com­mit­tee for Medicinal Products for Human Use (CHMP) in April 2020 and applies to all cur­rent dara­tu­mu­mab in­di­ca­tions in front­line and re­lapsed / re­frac­tory settings
• Approval based on data from Phase III COLUMBA and Phase II PLEIADES stud­ies
• In the stud­ies, the fixed-dose sub­cu­tane­ous for­mu­la­tion reduced treat­ment time from hours to min­utes and dem­onstrated similar ef­fi­cacy and safety with sig­nif­i­cantly fewer in­fusion-related reac­tions com­pared with the in­tra­venous for­mu­la­tion

Copenhagen, Denmark; June 4, 2020 – Genmab A/S (Nasdaq: GMAB) an­nounced to­day that the Euro­pean Com­mis­sion (EC) has granted mar­ket­ing authori­za­tion for the sub­cu­tane­ous (SC) for­mu­la­tion of DAR­ZA­LEX® (dara­tu­mu­mab), for the treat­ment of adult patients with mul­ti­ple myeloma in all cur­rently approved dara­tu­mu­mab in­tra­venous (IV) for­mu­la­tion in­di­ca­tions in front­line and re­lapsed / re­frac­tory settings. The ap­prov­al follows a Positive Opinion by the CHMP of the Euro­pean Medicines Agency (EMA) in April 2020. The SC for­mu­la­tion is admin­istered as a fixed-dose over approx­i­mately three to five min­utes, sig­nif­i­cantly less time than IV dara­tu­mu­mab, which is given over sev­er­al hours. Patients cur­rently on dara­tu­mu­mab IV will have the choice to switch to the SC for­mu­la­tion. In August 2012, Genmab granted Janssen Biotech, Inc. (Janssen) an ex­clu­sive world­wide license to de­vel­op, manu­fac­ture and com­mer­cialize dara­tu­mu­mab.

“We are extremely pleased that patients in Europe with mul­ti­ple myeloma will now, like patients in the U.S., have the oppor­tu­ni­ty for treat­ment with the sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab. With con­sis­tent ef­fi­cacy, and greater con­ve­nience for patients and health care providers with dosing time reduced from hours to just min­utes and fewer in­fusion-related reac­tions, this for­mu­la­tion provides sig­nif­i­cant ben­e­fits for patients,” said Jan van de Winkel, Ph.D., Chief Exec­u­tive Of­fi­cer of Genmab

The ap­prov­al was based on data from two stud­ies: the Phase III non-inferiority COLUMBA (MMY3012) study, which com­pared the SC for­mu­la­tion of dara­tu­mu­mab to the IV for­mu­la­tion in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma, and data from the Phase II PLEIADES (MMY2040) study, which is eval­u­ating SC dara­tu­mu­mab in com­bi­na­tion with cer­tain stan­dard mul­ti­ple myeloma regi­mens. The top­line re­­sults from the COLUMBA study were an­nounced in Feb­ru­ary 2019 and sub­se­quently pre­sented in oral sessions at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting and the 24th Euro­pean He­ma­tol­ogy Asso­ci­a­tion (EHA) Annual Congress. Updated data of the COLUMBA and the PLEIADES stud­ies were pre­sented during poster sessions at the 61st American Society of He­ma­tol­ogy (ASH) Annual Meeting in De­cem­ber 2019.

About the COLUMBA (MMY3012) study

The Phase III trial (NCT03277105) is a ran­dom­ized, open-label, parallel assignment study that in­cluded 522 adults diag­nosed with re­lapsed and re­frac­tory mul­ti­ple myeloma. Patients were ran­dom­ized to re­ceive either: SC dara­tu­mu­mab, as 1800 mg dara­tu­mu­mab with rHuPH20 2000 U/mL once weekly in Cycle 1 and 2, every two weeks in Cycles 3 to 6, every 4 weeks in Cycle 7 and there­after until dis­ease pro­gres­sion, un­ac­cept­able toxicity or the end of study; or 16 mg/kg IV dara­tu­mu­mab once weekly in Cycle 1 and 2, every two weeks in Cycles 3 to 6, every 4 weeks in Cycle 7 and there­after until dis­ease pro­gres­sion, un­ac­cept­able toxicity or the end of study. The co-primary end­points of the study are over­all re­sponse rate and Maximum trough con­cen­tra­tion of dara­tu­mu­mab (C_trough; defined as the serum pre-dose con­cen­tra­tion of dara­tu­mu­mab on Cycle 3 Day 1).

About the PLEIADES (MMY2040) study

The Phase II trial (NCT03412565) is a non-randomized, open-label, parallel assignment study that in­cludes 265 adults either newly diag­nosed or with re­lapsed or re­frac­tory mul­ti­ple myeloma. Patients with newly diag­nosed mul­ti­ple myeloma are being treated with 1,800 mg SC dara­tu­mu­mab in com­bi­na­tion with either bor­tez­o­mib, lena­lido­mide and dexa­meth­a­sone (D-VRd) or bor­tez­o­mib, mel­phalan and pred­ni­sone (D-VMP). Patients with re­lapsed or re­frac­tory mul­ti­ple myeloma are being treated with 1,800 mg SC dara­tu­mu­mab plus lena­lido­mide and dexa­meth­a­sone (D-Rd). An addi­tional cohort of patients with re­lapsed and re­frac­tory mul­ti­ple myeloma treated with dara­tu­mu­mab plus car­filz­o­mib and dexa­meth­a­sone (D-Kd) was sub­se­quently added to the study. The pri­mary end­point for the D-VMP, D-Kd and D-Rd cohorts is over­all re­sponse rate. The pri­mary end­point for the D-VRd cohort is very good partial re­sponse or better rate.

About DAR­ZA­LEX® (dara­tu­mu­mab)

DARZALEX® (dara­tu­mu­mab) in­tra­venous in­fusion is in­di­cated for the treat­ment of adult patients in the United States: in com­bi­na­tion with bor­tez­o­mib, thalido­mide and dexa­meth­a­sone as treat­ment for patients newly diag­nosed with mul­ti­ple myeloma who are eli­gible for au­tol­o­gous stem cell trans­plant; in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant; in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant; in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, or bor­tez­o­mib and dexa­meth­a­sone, for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived at least one prior ther­apy; in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived at least two prior ther­a­pies, in­clud­ing lena­lido­mide and a pro­te­a­some in­hib­i­tor (PI); and as a mono­therapy for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived at least three prior lines of ther­apy, in­clud­ing a PI and an immuno­modu­la­tory agent, or who are double-refractory to a PI and an immuno­modu­la­tory agent.¹ DAR­ZA­LEX is the first mono­clonal anti­body (mAb) to re­ceive U.S. Food and Drug Admin­istra­tion (U.S. FDA) ap­prov­al to treat mul­ti­ple myeloma.

DARZALEX is in­di­cated for the treat­ment of adult patients in Europe via in­tra­venous in­fusion or sub­cu­tane­ous admin­istra­tion: in com­bi­na­tion with bor­tez­o­mib, thalido­mide and dexa­meth­a­sone as treat­ment for patients newly diag­nosed with mul­ti­ple myeloma who are eli­gible for au­tol­o­gous stem cell trans­plant; in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant; in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of adult patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant; 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; and as mono­therapy for the treat­ment of adult patients with re­lapsed and re­frac­tory mul­ti­ple myeloma, whose prior ther­apy in­cluded a PI and an immuno­modu­la­tory agent and who have dem­onstrated dis­ease pro­gres­sion on the last ther­apy². Dara­tu­mu­mab is the first sub­cu­tane­ous CD38-directed anti­body approved in Europe for the treat­ment of mul­ti­ple myeloma. The op­tion to split the first in­fusion of DAR­ZA­LEX over two con­sec­u­tive days has been approved in both Europe and the U.S.

In Japan, DAR­ZA­LEX in­tra­venous in­fusion is approved for the treat­ment of adult patients: in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant; in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant; in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, or bor­tez­o­mib and dexa­meth­a­sone for the treat­ment of re­lapsed or re­frac­tory mul­ti­ple myeloma. DAR­ZA­LEX is the first human CD38 mono­clonal anti­body to reach the mar­ket in the United States, Europe and Japan. For more in­for­ma­tion, visit www.DARZALEX.com.

DARZALEX FASPRO™ (dara­tu­mu­mab and hyal­uron­i­dase-fihj), a sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab, is approved in the United States for the treat­ment of adult patients with mul­ti­ple myeloma: in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone in newly diag­nosed patients who are in­eli­gible for ASCT; in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone in newly diag­nosed patients who are in­eli­gible for ASCT and in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma who have re­ceived at least one prior ther­apy; in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone in patients who have re­ceived at least one prior ther­apy; and as mono­therapy, in patients who have re­ceived at least three prior lines of ther­apy in­clud­ing a PI and an immuno­modu­la­tory agent or who are double-refractory to a PI and an immuno­modu­la­tory agent.³ DAR­ZA­LEX FASPRO is the first sub­cu­tane­ous CD38-directed anti­body approved in the U.S. for the treat­ment of mul­ti­ple myeloma.

Daratumumab is a human IgG1k mono­clonal anti­body (mAb) that binds with high affinity to the CD38 mol­e­cule, which is highly ex­pressed on the surface of mul­ti­ple myeloma cells. Dara­tu­mu­mab triggers a person’s own im­mune sys­tem to attack the can­cer cells, re­sult­ing in rapid tumor cell death through mul­ti­ple im­mune-mediated mech­a­nisms of action and through immuno­modu­la­tory effects, in addi­tion to direct tumor cell death, via apop­tosis (programmed cell death).^1,4,5,6,7

Daratumumab is being devel­oped by Janssen Biotech, Inc. under an ex­clu­sive world­wide license to de­vel­op, manu­fac­ture and com­mer­cialize dara­tu­mu­mab from Genmab. A com­pre­hen­sive clin­i­cal de­vel­op­ment pro­gram for dara­tu­mu­mab is on­go­ing, in­clud­ing mul­ti­ple Phase III stud­ies in smol­der­ing, re­lapsed and re­frac­tory and front­line mul­ti­ple myeloma settings. Addi­tional stud­ies are on­go­ing or planned to assess the poten­tial of dara­tu­mu­mab in other malignant and pre-malignant dis­eases in which CD38 is ex­pressed, such as amy­loid­osis and T-cell acute lym­pho­cytic leukemia (ALL). Dara­tu­mu­mab has re­ceived two Break­­through Therapy Desig­na­tions from the U.S. FDA for cer­tain in­di­ca­tions of mul­ti­ple myeloma, in­clud­ing as a mono­therapy for heavily pre­treated mul­ti­ple myeloma and in com­bi­na­tion with cer­tain other ther­a­pies for sec­ond-line treat­ment of mul­ti­ple myeloma.

About Genmab

Genmab is a pub­licly traded, inter­na­tional bio­technol­ogy com­pany spe­cializing in the creation and de­vel­op­ment of dif­fer­en­ti­ated anti­body thera­peutics for the treat­ment of can­cer. Founded in 1999, the com­pany is the creator of three approved anti­bodies: DAR­ZA­LEX® (dara­tu­mu­mab, under agree­ment with Janssen Biotech, Inc.) for the treat­ment of cer­tain mul­ti­ple myeloma in­di­ca­tions in territories in­clud­ing the U.S., Europe and Japan, Arzerra® (ofatumumab, under agree­ment with Novartis AG), for the treat­ment of cer­tain chronic lym­pho­cytic leukemia in­di­ca­tions in the U.S., Japan and cer­tain other territories and TEPEZZA™ (teprotumumab, under agree­ment with Roche granting sublicense to Horizon Thera­peutics plc) for the treat­ment of thyroid eye dis­ease in the U.S. A sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab, DAR­ZA­LEX FASPRO™ (dara­tu­mu­mab and hyal­uron­i­dase-fihj), has been approved in the U.S. for the treat­ment of adult patients with cer­tain mul­ti­ple myeloma in­di­ca­tions. Dara­tu­mu­mab is in clin­i­cal de­vel­op­ment by Janssen for the treat­ment of addi­tional mul­ti­ple myeloma in­di­ca­tions, other blood can­cers and amy­loid­osis. A sub­cu­tane­ous for­mu­la­tion of ofatumumab is in de­vel­op­ment by Novartis for the treat­ment of relapsing mul­ti­ple sclerosis. Genmab also has a broad clin­i­cal and pre-clinical prod­uct pipe­line. Genmab's tech­nology base con­sists of val­i­dated and pro­pri­e­tary next gen­er­a­tion anti­body tech­nolo­gies - the DuoBody® plat­form for gen­er­a­tion of bispecific anti­bodies, the HexaBody® plat­form, which creates effector function en­hanced anti­bodies, the HexElect® plat­form, which com­bines two co-depen­dently acting HexaBody mol­e­cules to introduce selectivity while maximizing thera­peutic potency and the DuoHexaBody® plat­form, which en­hances the poten­tial potency of bispecific anti­bodies through hexamerization. The com­pany in­tends to leverage these tech­nolo­gies to create oppor­tu­ni­ties for full or co-ownership of future prod­ucts. Genmab has alliances with top tier pharma­ceu­tical and bio­technol­ogy com­pa­nies. Genmab is headquartered in Copenhagen, Denmark with sites in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan.

Cautions Concerning Forward-Looking State­ments

This Com­pany Announcement con­tains for­ward looking state­ments. The words “believe”, “expect”, “anticipate”, “intend” and “plan” and similar ex­pres­sions identify for­ward looking state­ments. Actual re­­sults or per­for­mance may differ ma­teri­ally from any future re­­sults or per­for­mance ex­pressed or im­plied by such state­ments. The im­por­tant factors that could cause our actual re­­sults or per­for­mance to differ ma­teri­ally in­clude, among others, risks asso­ci­ated with pre-clinical and clin­i­cal de­vel­op­ment of prod­ucts, un­cer­tainties re­lated to the out­come and con­duct of clin­i­cal trials in­clud­ing un­fore­seen safety issues, un­cer­tainties re­lated to prod­uct manu­fac­tur­ing, the lack of mar­ket ac­ceptance of our prod­ucts, our in­abil­ity to man­age growth, the competitive en­viron­ment in rela­tion to our business area and mar­kets, our in­abil­ity to attract and retain suitably qualified per­son­nel, the un­en­force­ability or lack of pro­tec­tion of our pat­ents and pro­pri­e­tary rights, our rela­tion­ships with affiliated entities, changes and de­vel­op­ments in tech­nology which may render our prod­ucts or tech­nolo­gies obsolete, and other factors. For a fur­ther dis­cus­sion of these risks, please refer to the risk man­age­ment sections in Genmab’s most recent fi­nan­cial re­ports, which are avail­able on www.genmab.com and the risk factors in­cluded in Genmab’s most recent Annual Report on Form 20-F and other filings with the U.S. Se­cu­ri­ties and Ex­change Com­mis­sion (SEC), which are avail­able at www.sec.gov. Genmab does not under­take any obli­ga­tion to up­date or revise for­ward looking state­ments in this Com­pany Announcement nor to con­firm such state­ments to reflect sub­se­quent events or cir­cum­stances after the date made or in rela­tion to actual re­­sults, unless re­quired by law.

Genmab A/S and/or its sub­sid­i­aries own the fol­low­ing trade­marks: Genmab®; the Y-shaped Genmab logo®; Genmab in com­bi­na­tion with the Y-shaped Genmab logo®; HuMax®; DuoBody®; DuoBody in com­bi­na­tion with the DuoBody logo®; HexaBody®; HexaBody in com­bi­na­tion with the HexaBody logo®; DuoHexaBody®; HexElect®; and UniBody®. Arzerra® is a trade­mark of Novartis AG or its affiliates. DAR­ZA­LEX® and DAR­ZA­LEX FASPRO™ are trade­marks of Janssen Pharmaceutica NV. TEPEZZA™ is a trade­mark of Horizon Thera­peutics plc.

References

1. DARZALEX Prescribing in­for­ma­tion, April 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761036s027lbl.pdf Last accessed April 2020
2. DARZALEX Summary of Product Characteristics, avail­able at https://www.ema.europa.eu/en/medicines/human/EPAR/darzalex Last accessed Octo­ber 2019
3. DARZALEX FASPRO Prescribing in­for­ma­tion, May 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761145s000lbl.pdf Last accessed May 2020
4. De Weers, M et al. Dara­tu­mu­mab, a Novel Thera­peutic Human CD38 Monoclonal Anti­body, Induces Killing of Multiple Myeloma and Other Hema­to­logical Tumors. The Journal of Immunology. 2011; 186: 1840-1848.
5. Overdijk, MB, et al. Anti­body-mediated phago­cytosis con­trib­utes to the anti-tumor ac­­tiv­ity of the thera­peutic anti­body dara­tu­mu­mab in lym­phoma and mul­ti­ple myeloma. MAbs. 2015; 7: 311-21.
6. Krejcik, MD et al. Dara­tu­mu­mab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94.
7. Jansen, JH et al. Dara­tu­mu­mab, a human CD38 anti­body induces apop­tosis of myeloma tumor cells via Fc re­cep­tor-mediated crosslinking. Blood. 2012; 120(21): abstract 2974

Source: Genmab.