• DARZALEX (dara­tu­mu­mab) approved by U.S. FDA 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
• First approval for DARZALEX in a frontline indi­ca­tion

Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq Copenhagen: GEN) announced today that the U.S. Food and Drug Admin­istra­tion (U.S. FDA) has approved the use of DARZALEX® (dara­tu­mu­mab) in combi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone (VMP) for the treat­ment of patients with newly diag­nosed multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant (ASCT). The supple­mental Biologics License Appli­cation (sBLA) for this indi­ca­tion was submitted by Genmab’s licensing part­ner, Janssen Biotech, Inc., in November 2017. The U.S. FDA sub­se­quently granted priority review to the sBLA, with a Prescription Drug User Fee Act (PDUFA) target date of May 21, 2018. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive world­wide license to develop, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab.

“With this label expansion, DARZALEX be­comes the first anti­body thera­peutic to be approved for patients with newly diag­nosed multiple myeloma,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “This is an im­por­tant step for­ward as it provides an addi­tional treat­ment option to patients who are newly diag­nosed with multiple myeloma.”

The approval was based on data from the Phase III ALCYONE study that showed a reduction of the risk of disease pro­gres­sion or death by 50 per­cent (Hazard Ratio [HR] = 0.50; 95 per­cent CI [0.38-0.65], p<0.0001) in patients with newly diag­nosed multiple myeloma in­eli­gible for ASCT when dara­tu­mu­mab is com­bined with VMP. The safety of DARZALEX combi­na­tion ther­apy was con­sis­tent with the known safety profiles of DARZALEX mono­therapy and of ther­apy with bor­tez­o­mib, mel­phalan and pred­nisone, re­spec­tive­ly. This data was presented as a Late-Breaking Abstract at the 2017 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The New England Journal of Medicine in December, 2017.

About the ALCYONE study

This Phase III study (NCT02195479) is a ran­domized, open-label, multi­center study that in­cluded 706 newly diag­nosed patients with multiple myeloma who are in­eli­gible for ASCT. Patients were ran­domized to receive 9 cycles of either VMP [bortezomib (a pro­te­a­some inhibitor), mel­phalan (an alkylating chemotherapeutic agent) and pred­ni­sone (a cortico­steroid)] com­bined with dara­tu­mu­mab, or VMP alone. In the dara­tu­mu­mab treat­ment arm, patients received 16 mg/kg of dara­tu­mu­mab once weekly for six weeks (cycle 1; 1 cycle = 42 days), once every three weeks from cycles 2 to 9, and once every 4 weeks from cycle 9 until disease pro­gression. The pri­mary end­point of the study is pro­gres­sion free survival (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 30,770 new patients are ex­pec­ted to be diag­nosed with multiple myeloma and approx­i­mately 12,770 people are ex­pec­ted to die from the disease in the U.S. in 2018.³ Globally, it was esti­mated that 124,225 people would be diag­nosed and 87,084 would die from the disease in 2015.⁴ 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) 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 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 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. In Japan, DARZALEX is approved in combi­na­tion with lena­lido­mide and dexa­meth­a­sone, or bor­tez­o­mib and dexa­meth­a­sone, for treat­ment of adults with re­lapsed or refractory multiple myeloma. DARZALEX is the first human CD38 mono­clonal anti­body to reach the mar­ket. 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 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, myelo­dys­plastic syn­dromes, B and T-ALL and selected solid tumors. 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, other blood cancers, and solid tumors. 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, and the HexaBody® plat­form which creates effector function en­hanced anti­bodies. 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.

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®; 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. American Cancer Society. "What are the key statistics about multiple myeloma?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed March 2018
4. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide: Number of New Cancers in 2015. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=0&window=1&submit=%C2%A0Execute. Accessed June 2016.
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, June 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761036s005lbl.pdf Last accessed June 2017
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.