• BLA sub­mitted to U.S. FDA for sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab
• Submission based on data from Phase III COLUMBA and Phase II PLEIADES stud­ies

Copenhagen, Denmark (Company Announcement) – Genmab A/S (Nasdaq Copenhagen: GEN) an­nounced to­day that its licensing part­ner, Janssen Biotech, Inc., has sub­mitted a Biologics License Appli­ca­tion (BLA) to the U.S. Food and Drug Admin­istra­tion (U.S. FDA) for the use of the sub­cu­tane­ous (SubQ) for­mu­la­tion of dara­tu­mu­mab in mul­ti­ple myeloma indi­ca­tions where the in­tra­venous for­mu­la­tion of dara­tu­mu­mab is cur­rently approved. In August 2012, Genmab granted Janssen an ex­clu­sive world­wide license to de­vel­op, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab.

“Should this sub­mission lead to an ap­­prov­al, it would provide patients with a treat­ment op­tion that com­bines ef­fi­cacy com­parable with in­tra­venous DAR­ZA­LEX® with a sub­cu­tane­ous de­livery that reduces treat­ment time from hours to just min­utes. Not only would this be more con­ve­nient for patients but, as we saw with the COLUMBA data recently pre­sented at the 2019 ASCO Annual Meeting and 24th EHA Annual Congress, in­fusion-related reac­tions are both mild and sig­nif­i­cantly reduced with this for­mu­la­tion of dara­tu­mu­mab,” said Jan van de Winkel, Ph.D., Chief Exec­u­tive Of­fi­cer of Genmab. “Subcutaneous dara­tu­mu­mab may also provide an attractive op­tion for health care providers, especially in the com­munity setting, where reducing the admin­istra­tion time can be very im­por­tant.”

The sub­mission is based on data from two on­go­ing stud­ies: the Phase III non-inferiority COLUMBA study, which is com­par­ing the sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab to the in­tra­venous for­mu­la­tion in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma and pre­lim­i­nary non-public data from the Phase II PLEIADES study, which is eval­u­ating dara­tu­mu­mab in com­bi­na­tion with cer­tain stan­dard mul­ti­ple myeloma regi­mens. The top­line re­­sults from the COLUMBA data were an­nounced in Feb­ru­ary 2019 and sub­se­quently pre­sented in oral sessions at the 2019 American Society of Clinical Oncology Annual Meeting and the 24th Euro­pean Hema­tol­ogy Asso­ci­a­tion Annual Congress.

About the COLUMBA (MMY3012) study

The Phase III trial (NCT03277105) is a ran­dom­ized, open-label, parallel assignment study that in­cludes 522 adults diag­nosed with re­lapsed and re­frac­tory mul­ti­ple myeloma. Patients were ran­dom­ized to re­ceive either: SubQ dara­tu­mu­mab, as 1800 mg dara­tu­mu­mab with rHuPH20 2000 U/mL once weekly in Cycle 1 and 2, every two weeks in Cycle 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 Cycle 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 240 adults either newly diag­nosed or with re­lapsed or re­frac­tory mul­ti­ple myeloma. Patients with newly diag­nosed mul­ti­ple myeloma are being treated with 1,800 mg sub­cu­tane­ous 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 sub­cu­tane­ous 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 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 in Europe 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 ther­apy. 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 is approved in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, or bor­tez­o­mib and dexa­meth­a­sone, for the treat­ment of adults with re­lapsed or re­frac­tory mul­ti­ple myeloma. DAR­ZA­LEX is the first human CD38 mono­clonal anti­body to reach the mar­ket in the United Stated, Europe and Japan.

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).^1,2,3,4,5

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, NKT-cell lym­phoma and B-cell and T-cell 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 has two approved anti­bodies, DAR­ZA­LEX® (dara­tu­mu­mab) for the treat­ment of cer­tain mul­ti­ple myeloma indi­ca­tions, and Arzerra® (ofatumumab) for the treat­ment of cer­tain chronic lym­pho­cytic leukemia indi­ca­tions. Dara­tu­mu­mab is in clin­i­cal devel­op­ment for addi­tional mul­ti­ple myeloma indi­ca­tions, other blood can­cers and amy­loid­osis. A sub­cu­tane­ous for­mu­la­tion of ofatumumab is in devel­op­ment for relapsing mul­ti­ple sclerosis. Genmab also has a broad clin­i­cal and pre-clinical prod­uct pipe­line. Genmab's tech­nology base in­cludes a num­ber of pro­pri­e­tary next gen­er­a­tion anti­body. Genmab has alliances with other lead­ing pharma­ceu­tical and bio­technology com­pa­nies.

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 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. 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® is a trade­mark of Janssen Pharmaceutica NV.

References

1. DARZALEX Prescribing in­for­ma­tion, June 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s020lbl.pdf Last accessed June 2019
2. 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.
3. 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.
4. 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.
5. 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.