• Phase III CANDOR study of dara­tu­mu­mab in com­bi­na­tion with car­filz­o­mib and dexa­meth­a­sone in re­lapsed or re­frac­tory mul­ti­ple myeloma met the pri­mary end­point of im­prove­ment in pro­gres­sion free sur­vival
• Data to be discussed with health author­i­ties in preparation for regu­la­tory sub­missions

Copenhagen, Denmark (Company Announcement) – Genmab A/S (Nasdaq: GMAB) an­nounced to­day top­line re­­sults from the Phase III CANDOR study, sponsored by Amgen, of dara­tu­mu­mab in com­bi­na­tion with car­filz­o­mib and dexa­meth­a­sone (Kd) versus Kd alone in patients with mul­ti­ple myeloma who have re­lapsed after one to three prior ther­a­pies. The study met the pri­mary end­point of im­prov­ing pro­gres­sion free sur­vival (PFS). The regi­men re­­sulted in a 37% re­duc­tion in the risk of pro­gres­sion or death in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma treated with dara­tu­mu­mab in com­bi­na­tion with Kd (HR=0.630; 95% CI: 0.464, 0.854; p=0.0014). The median PFS for patients treated with dara­tu­mu­mab in com­bi­na­tion with Kd had not been reached by the cut-off date com­pared to a median PFS of 15.8 months for patients who re­ceived Kd alone.

There was a higher frequency of ad­verse events re­ported with dara­tu­mu­mab plus Kd, a three-agent regi­men, than with Kd, a two-agent regi­men. The types of ob­served ad­verse events were con­sis­tent with the known safety profiles of the in­di­vid­ual agents. The most fre­quently re­ported treat­ment-emergent ad­verse events (greater than or equal to 20%) in the dara­tu­mu­mab plus Kd arm were thrombo­cyto­penia, anemia, diarrhea, hyper­tension, upper res­pira­tory tract in­fec­tion, fatigue and dyspnea.

The CANDOR data will be sub­mitted to a future med­i­cal meeting and Amgen will discuss the data with health author­i­ties in preparation for regu­la­tory sub­missions.

“We are very pleased that dara­tu­mu­mab has shown ef­fi­cacy in yet another com­bi­na­tion regi­men – in this case with car­filz­o­mib, a newer member of the pro­te­a­some in­hib­i­tor class. We look for­ward to the poten­tial for this com­bi­na­tion to provide an addi­tional regi­men for patients diag­nosed with re­lapsed mul­ti­ple myeloma,” said Jan van de Winkel, Ph.D., Chief Exec­u­tive Of­fi­cer of Genmab.

In August 2012, Genmab granted Janssen Biotech, Inc. an ex­clu­sive world­wide license to de­vel­op, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab.

About the CANDOR study

The Phase III trial (NCT03158688) is a ran­dom­ized, open-label study that in­cludes approx­i­mately 460 patients with mul­ti­ple myeloma who have re­lapsed after 1 to 3 prior ther­a­pies. Patients were ran­dom­ized to re­ceive either dara­tu­mu­mab in com­bi­na­tion with car­filz­o­mib (a pro­te­a­some in­hib­i­tor) and dexa­meth­a­sone (a corticosteroid) or car­filz­o­mib and dexa­meth­a­sone alone. In the dara­tu­mu­mab treat­ment arm, patients re­ceived 8 milligrams per kilo­gram (mg/kg) on days 1 and 2 of cycle 1, then 16 mg/kg once weekly for the re­main­ing doses of the first 2 cycles, then every 2 weeks for 4 cycles (cycles 3 to 6), and then every 4 weeks for the re­main­ing cycles or until dis­ease pro­gres­sion. In both treat­ment arms car­filz­o­mib was dosed twice weekly (20 mg/m² on cycle 1 days 1 and 2 and 56 mg/m² beginning on cycle 1 day 8 and there­after) and dexa­meth­a­sone was given weekly (40 mg orally or via IV in­fusion). The pri­mary end­point of the study is PFS.

About mul­ti­ple myeloma

Multiple myeloma is an incurable blood can­cer that starts in the bone mar­row and is char­ac­ter­ized by an excess pro­lif­er­a­tion of plasma cells.¹ Multiple myeloma is the third most common blood can­cer in the U.S., after leukemia and lym­phoma.² Approximately 26,000 new patients were ex­pec­ted to be diag­nosed with mul­ti­ple myeloma and approx­i­mately 13,650 people were ex­pec­ted to die from the dis­ease in the U.S. in 2018.³ Globally, it was esti­mated that 160,000 people were diag­nosed and 106,000 died from the dis­ease in 2018.⁴ While some patients with mul­ti­ple myeloma have no symp­toms at all, most patients are diag­nosed due to symp­toms which can in­clude bone prob­lems, low blood counts, cal­cium elevation, kidney prob­lems or in­fec­tions.⁵

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.6 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 and 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. 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.

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).^6,7,8,9,10

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 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 core sites in Utrecht, the Netherlands and Princeton, New Jersey, U.S.

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 final pros­pect­us for our U.S. pub­lic offering and listing 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® is a trade­mark of Janssen Pharmaceutica NV.

References

1. American Cancer Society. "Multiple Myeloma Overview." Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed June 2016.
2. National Cancer Institute. "A Snapshot of Myeloma." Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed June 2016.
3. Globocan 2018. United States of America Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/840-united-states-of-america-fact-sheets.pdf.
4. Globocan 2018. World Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed De­cem­ber 2018.
5. American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 2016.
6. DARZALEX Prescribing in­for­ma­tion, July 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s019lbl.pdf Last accessed July 2019
7. 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.
8. 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.
9. 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.
10.  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.