• DARZALEX® approved in Europe in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone as treat­ment for adult patients with newly diag­nosed multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant
• Approval follows pos­i­tive opinion by European Com­mit­tee for Medicinal Products for Human Use (CHMP) in Octo­ber
• Approval based on data from Phase III MAIA study

Copenhagen, Denmark (Company Announcement) – Genmab A/S (Nasdaq: GMAB) announced today that the European Com­mis­sion (EC) has granted mar­ket­ing authori­za­tion for DARZALEX® (dara­tu­mu­mab) in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (Rd) as treat­ment for adult patients with newly diag­nosed multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant (ASCT). The EC approval follows a pos­i­tive opinion issued for DARZALEX by the CHMP of the European Medicines Agency (EMA) in Octo­ber 2019. In August 2012, Genmab granted Janssen Biotech, Inc. (Janssen) an ex­clu­sive world­wide license to de­vel­op, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab.

“We are pleased that with this approval, patients in the European Union newly diag­nosed with multiple myeloma who are not can­di­dates for trans­plant will now have two poten­tial options for treat­ment with DARZALEX con­taining regi­mens. We look for­ward to seeing the com­bi­na­tion ther­apy of DARZALEX with lena­lido­mide and dexa­meth­a­sone launched in Europe,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The approval was based on data from the Phase III MAIA (MMY3008) study of dara­tu­mu­mab in com­bi­na­tion with Rd as treat­ment for patients with newly diag­nosed multiple myeloma, who are not can­di­dates for high dose chemo­ther­apy and ASCT. Data from this study was published in The New England Journal of Medicine and was presented as a Late-Breaking Abstract at the 2018 American Society of Hematology (ASH) Annual Meeting in De­cem­ber 2018.

About the MAIA (MMY3008) study

The Phase III study (NCT02252172) is a ran­dom­ized, open-label, multi­center study that in­cludes 737 newly diag­nosed patients with multiple myeloma who are not can­di­dates for high dose chemo­ther­apy and ASCT. Patients were ran­dom­ized to re­ceive either treat­ment with dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide (an immuno­modu­la­tory drug) and dexa­meth­a­sone (a corticosteroid) or treat­ment with lena­lido­mide and dexa­meth­a­sone alone. In the dara­tu­mu­mab treat­ment arm, patients re­ceived 16 milligrams per kilo­gram (mg/kg) weekly for the first 8 weeks (Cycles 1 and 2), every other week for 16 weeks (Cycles 3 to 6) and then every 4 weeks (Cycle 7 and beyond) until pro­gres­sion of dis­ease or unacceptable toxicity. Lena­lido­mide is admin­istered at 25 mg orally on days 1 through 21 of each 28-day cycle, and dexa­meth­a­sone is admin­istered at 40 mg once a week for both treat­ment arms. Participants in both treat­ment arms will con­tinue Rd until dis­ease pro­gres­sion or unacceptable toxicity. The pri­mary end­point of the study is pro­gres­sion free sur­vival.

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 Approximately 16,830 new patients were ex­pec­ted to be diag­nosed with multiple myeloma and approx­i­mately 10,480 people were ex­pec­ted to die from the dis­ease in the Western Europe in 2018.² Globally, it was esti­mated that 160,000 people were diag­nosed and 106,000 died from the dis­ease in 2018.³ 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.⁴

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.⁵ 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 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 ther­apy⁶. 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, or bor­tez­o­mib and dexa­meth­a­sone for the treat­ment of re­lapsed or re­frac­tory multiple myeloma; 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).^5,6,7,8,9,10

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. Globocan 2018. Western Europe Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/926-western-europe-fact-sheets.pdf Accessed March 2018
3. Globocan 2018. World Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed De­cem­ber 2018.
4. American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 2016
5. DARZALEX Prescribing in­for­ma­tion, Sep­tem­ber 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s024lbl.pdf Last accessed Sep­tem­ber 2019
6. DARZALEX Summary of Product Characteristics, avail­able at https://www.ema.europa.eu/en/medicines/human/EPAR/darzalex Last accessed Octo­ber 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.