• Subcutaneous for­mu­la­tion of dara­tu­mu­mab, DAR­ZA­LEX FASPRO™, approved by the U.S. FDA for the treat­ment of patients with mul­ti­ple myeloma
• 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

{{image}}Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq: GMAB) an­nounced to­day that the U.S. Food and Drug Admin­istra­tion (U.S. FDA) has approved the use of the sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab, DAR­ZA­LEX FASPRO™ (dara­tu­mu­mab and hyal­uron­i­dase-fihj). The Biologics License Appli­ca­tion (BLA) for this for­mu­la­tion was sub­mitted by Genmab’s licensing part­ner, Janssen Biotech, Inc. (Janssen) in July 2019. DAR­ZA­LEX FASPRO is approved for the treat­ment of adult patients with mul­ti­ple myeloma: in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone in newly diag­nosed patients who are in­eli­gible for au­tol­o­gous stem cell trans­plant (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 pro­te­a­some in­hib­i­tor (PI) and an immuno­modu­la­tory agent or who are double-refractory to a PI and an immuno­modu­la­tory agent. DAR­ZA­LEX FASPRO is a fixed-dose for­mu­la­tion that can be admin­istered over approx­i­mately three to five min­utes, sig­nif­i­cantly less time than in­tra­venous DAR­ZA­LEX®, which is given over sev­er­al hours. In August 2012, Genmab granted Janssen an ex­clu­sive world­wide license to de­vel­op, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab.

The ap­­prov­al was based on data from two stud­ies: the Phase III non-inferiority COLUMBA (MMY3012) study, which com­pared the sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab to the in­tra­venous for­mu­la­tion in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma and data from the Phase II PLEIADES (MMY2040) study, which is eval­u­ating sub­cu­tane­ous dara­tu­mu­mab in com­bi­na­tion with dif­fer­en­t stan­dard mul­ti­ple myeloma treat­ment 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. An up­date of the COLUMBA data as well as data from the PLEIADES study were pre­sented during poster sessions at the 61st American Society of Hema­tol­ogy (ASH) Annual Meeting in De­cem­ber 2019.

“The ap­­prov­al of the sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab, DAR­ZA­LEX FASPRO, is a landmark event in the de­vel­op­ment of dara­tu­mu­mab. Not only is it now the first and only sub­cu­tane­ous CD38 anti­body approved for the treat­ment of mul­ti­ple myeloma, the sub­cu­tane­ous admin­istra­tion of DAR­ZA­LEX FASPRO con­siderably reduces treat­ment burden, as the fixed-dose in­jec­tion is admin­istered in approx­i­mately three to five min­utes, offering patients a more con­ve­nient treat­ment ex­peri­ence. As seen in the pivotal study sup­port­ing the ap­­prov­al, this re­duc­tion in in­fusion time from hours to min­utes led to higher satisfaction levels for patients and in addi­tion, in­fusion-related reac­tions were both mild and sig­nif­i­cantly reduced with this for­mu­la­tion of dara­tu­mu­mab. We are very much looking for­ward to the launch of DAR­ZA­LEX FASPRO in the U.S. and the poten­tial for pos­i­tive im­pact it will have on the lives of the patients re­ceiv­ing the drug,” said Jan van de Winkel, Ph.D., Chief Exec­u­tive Of­fi­cer of Genmab.

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: sub­cu­tane­ous (SC) dara­tu­mu­mab, as 1,800 mg dara­tu­mu­mab with rHuPH20 2,000 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 (Ctrough; 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 (ASCT); in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for ASCT; in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for ASCT; 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 in­tra­venous in­fusion is in­di­cated for the treat­ment of adult patients in Europe: in com­bi­na­tion with bor­tez­o­mib, thalido­mide and dexa­meth­a­sone as treat­ment for patients newly diag­nosed with mul­ti­ple myeloma who are eli­gible for ASCT; in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for ASCT; in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of adult patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for ASCT; 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. 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 ASCT; in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of patients with newly diag­nosed mul­ti­ple myeloma who are in­eli­gible for ASCT; 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. 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, resul cvfting 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).^1,2,3,4,5,6

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. 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. 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.
4. 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.
5. 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.
6. 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.