• Phase III COLUMBA study com­par­ing the sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab to the in­tra­venous for­mu­la­tion in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma met both co-primary end­points
• Results show that dara­tu­mu­mab admin­istered sub­cu­tane­ously was non-inferior in ef­fi­cacy and phar­ma­co­ki­netics as com­pared to dara­tu­mu­mab admin­istered in­tra­venously
• Data will be discussed with health author­i­ties to prepare for regu­la­tory filings in sup­port of bringing con­ve­nience of sub­cu­tane­ous dara­tu­mu­mab op­tion to patients

Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq Copenhagen: GEN) an­nounced to­day top­line re­­sults from the Phase III COLUMBA study (MMY3012) of sub­cu­tane­ous (SC) versus in­tra­venous (IV) dara­tu­mu­mab for patients with re­lapsed or re­frac­tory mul­ti­ple myeloma. The re­­sults showed that SC admin­istra­tion of dara­tu­mu­mab co-formulated with recombinant human hyal­uron­i­dase PH20 is non-inferior to IV admin­istra­tion of dara­tu­mu­mab with regard to the co-primary end points of over­all re­sponse rate (ORR) and Maximum Trough con­cen­tra­tion (C_trough) of dara­tu­mu­mab on day 1 of the third treat­ment cycle.

The ORR for patients treated with SC dara­tu­mu­mab was 41.1% (n=263) versus 37.1% in patients treated with IV dara­tu­mu­mab (n= 259). The lower limit of the 95% Confidence Interval (CI) for the ratio of the two met the specified non-inferiority criterion for this co-primary end­point. The geometric mean of C_trough for patients treated with SC dara­tu­mu­mab was 499 mg/mL (n=149) versus 463 mg/mL in patients treated with IV dara­tu­mu­mab (n= 146). The lower limit of the 95% CI for the ratio of the two met the specified non-inferiority criterion for this co-primary end­point.

No new safety signals were detected and Janssen Biotech, Inc., which licensed dara­tu­mu­mab from Genmab in 2012, will discuss the poten­tial for a regu­la­tory sub­mission for this for­mu­la­tion with health author­i­ties, and plans to submit the data to an up­com­ing med­i­cal conference and for pub­li­ca­tion in a peer-reviewed journal.

“With the data from each of the key clin­i­cal stud­ies we learn more about the dif­fer­ence that dara­tu­mu­mab poten­tially can make to the lives of patients suffer­ing with mul­ti­ple myeloma. I am par­tic­u­larly ex­cited about the re­­sults from this study as it may sup­port a much quicker and far more con­ve­nient admin­istra­tion of dara­tu­mu­mab, which would provide an im­por­tant ben­e­fit for many patients and their families,” 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 in­cludes 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 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 ORR and Maximum trough of dara­tu­mu­mab (C_trough; defined as the serum pre dose con­cen­tra­tion of dara­tu­mu­mab on Cycle 3 Day 1).

About DAR­ZA­LEX® (dara­tu­mu­mab)

DARZALEX® (dara­tu­mu­mab) in­jec­tion for in­tra­venous in­fusion is in­di­cated in the United States 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. For more in­for­ma­tion, visit www.DARZALEX.com.

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 front­line mul­ti­ple myeloma settings and in amy­loid­osis. Addi­tional stud­ies are on­go­ing or planned to assess the poten­tial of dara­tu­mu­mab in other malignant and pre-malignant dis­eases, such as NKT-cell lym­phoma, B and T-ALL. Dara­tu­mu­mab has re­ceived two Break­through Therapy Desig­nations from the U.S. FDA, for mul­ti­ple myeloma, as both a mono­therapy and in com­bi­na­tion with other ther­a­pies.

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 and other blood can­cers. 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 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 and the HexElect™ plat­form, which com­bines two co-depen­dently acting HexaBody mol­e­cules to introduce selectivity while maximizing thera­peutic potency. 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. For more in­for­ma­tion visit www.genmab.com.

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, February 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s016lbl.pdf Last accessed February 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.