• Phase 3 APOLLO ran­dom­ized study eval­u­ating sub­cu­tane­ous dara­tu­mu­mab in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone versus poma­lido­mide and dexa­meth­a­sone alone in re­lapsed or re­frac­tory mul­ti­ple myeloma met the pri­mary end­point of im­prov­ing pro­gres­sion-free sur­vival
• Janssen in­tends to discuss the data with health author­i­ties for po­ten­tial regu­la­tory sub­missions

Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq: GMAB) an­nounced to­day that the Euro­pean Myeloma Network (EMN) in col­lab­o­ration with Janssen Re­search & De­vel­op­ment, LLC (Janssen) re­ported pos­i­tive re­­sults from the Phase 3 APOLLO (MMY3013) study of the sub­cu­tane­ous (SC) for­mu­la­tion of dara­tu­mu­mab in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone (Pd) versus Pd alone as treat­ment for patients with re­lapsed or re­frac­tory mul­ti­ple myeloma who have pre­vi­ously been treated with lena­lido­mide (an immuno­modu­la­tory drug) and a pro­te­a­some in­hib­i­tor (PI). The study met the pri­mary end­point of im­prov­ing pro­gres­sion-free sur­vival (PFS). Over­all, the safety profile of dara­tu­mu­mab SC in com­bi­na­tion with Pd was con­sis­tent with the safety profile for each ther­apy separately.

“We are pleased with these pos­i­tive re­­sults for dara­tu­mu­mab, admin­istered as a sub­cu­tane­ous for­mu­la­tion, in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone. The corresponding in­tra­venous regi­men was pre­vi­ously approved by the U.S. FDA based on the Phase1 single-arm EQUULEUS study,” said Jan van de Winkel, Ph.D., Chief Exec­u­tive Of­fi­cer of Genmab.

Janssen Biotech, Inc., which obtained an ex­clu­sive world­wide license to de­vel­op, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab from Genmab in 2012, in­tends to discuss the data with health author­i­ties in preparation for regu­la­tory sub­missions and plans to submit the data for pre­sen­ta­tion at an up­com­ing med­i­cal conference.

The APOLLO study was de­signed to con­firm the re­­sults from the Phase 1 EQUULEUS (MMY1001) study, which in­ves­ti­gated in­tra­venous (IV) dara­tu­mu­mab plus Pd in the same in­di­ca­tion. In June 2017, the U.S. Food and Drug Admin­istra­tion (U.S. FDA) approved the use of DAR­ZA­LEX in com­bi­na­tion with Pd for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived at least two prior ther­a­pies in­clud­ing lena­lido­mide and a PI based on the re­­sults of the EQUULEUS study.

About the APOLLO (MMY3013) study

This Phase 3 (NCT03180736), ran­dom­ized, open-label, multi­center study in­cluded 304 patients with mul­ti­ple myeloma who have pre­vi­ously been treated with lena­lido­mide and a PI. Patients were ran­dom­ized 1:1 to either re­ceive dara­tu­mu­mab in com­bi­na­tion with Pd or Pd alone. In the original design of the study, patients in the dara­tu­mu­mab plus Pd arm were treated with the IV for­mu­la­tion of dara­tu­mu­mab. As of Amendment 1, all new subjects in the ex­per­i­men­tal arm were dosed with the SC for­mu­la­tion of dara­tu­mu­mab and patients who had already begun treat­ment with IV dara­tu­mu­mab had the op­tion to switch to the SC for­mu­la­tion. The pri­mary end­point of the study was PFS. The study was con­ducted in Europe under an agree­ment be­tween Janssen, EMN and Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON).

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 esti­mated diag­nosed with mul­ti­ple myeloma and approx­i­mately 13,650 people were ex­pected to have died 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 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.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 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 ther­apy⁷. 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.⁸ 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).^6,9,10,11,12

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, known as DAR­ZA­LEX FASPRO™ (dara­tu­mu­mab and hyal­uron­i­dase-fihj) in the U.S., has been approved in the U.S. and Europe 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. 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, Sep­tem­ber 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s024lbl.pdf Last accessed Sep­tem­ber 2019
7. DARZALEX Summary of Product Characteristics, avail­able at https://www.ema.europa.eu/en/medicines/human/EPAR/darzalex Last accessed June 2020
8. DARZALEX FASPRO Prescribing in­for­ma­tion, May 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761145s000lbl.pdf Last accessed May 2020
9. 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.
10. 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.
11. 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.
12. 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.