• DARZALEX (dara­tu­mu­mab) approved by U.S. FDA in com­bi­na­tion with bor­tez­o­mib, thalido­mide (an immuno­modu­la­tory agent) and dexa­meth­a­sone as treat­ment for patients newly diag­nosed with multiple myeloma who are eli­gible for au­tol­o­gous stem cell trans­plant
• Approval based on Phase III CASSIOPEIA study

Copenhagen, Denmark (Company Announcement) – Genmab A/S (Nasdaq: GMAB) announced today that the U.S. Food and Drug Admin­istra­tion (U.S. FDA) has approved the use of DARZALEX® (dara­tu­mu­mab) in com­bi­na­tion with bor­tez­o­mib, thalido­mide and dexa­meth­a­sone (VTd) as treat­ment for patients newly diag­nosed with multiple myeloma who are eli­gible 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. (Janssen) in March 2019. The U.S. FDA sub­se­quently granted priority review to the sBLA, with a Prescription Drug User Fee Act (PDUFA) target date of Sep­tem­ber 26, 2019. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive world­wide license to develop, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab.

The approval was based on data from part one of the Phase III CASSIOPEIA study of dara­tu­mu­mab in com­bi­na­tion with VTd as treat­ment for patients newly diag­nosed with multiple myeloma who are can­di­dates for ASCT. The study is sponsored by the French Intergroupe Francophone du Myelome (IFM) in col­lab­o­ration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen.

“Today’s approval is an im­por­tant step for­ward for patients with multiple myeloma. There are now three dif­fer­en­t treat­ment com­bi­na­tions that in­clude DARZALEX for patients newly diag­nosed with multiple myeloma, whether they are eli­gible for ASCT or not. We are grateful for the efforts of the IMF, HOVON and Janssen that led to the strong data from the CASSIOPEIA trial, which formed the basis of this new approval,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the CASSIOPEIA (MMY3006) study

This Phase III study is a ran­dom­ized, open-label, multi­center study, run by the French Intergroupe Francophone du Myelome (IFM) in col­lab­o­ration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen, in­clud­ing 1,085 newly diag­nosed patients with pre­vi­ously untreated symp­tomatic multiple myeloma who are eli­gible for high dose chemo­ther­apy and stem cell trans­plant. In the first part of the study, patients were ran­dom­ized to receive induction and con­sol­i­da­tion treat­ment with dara­tu­mu­mab com­bined with bor­tez­o­mib, thalido­mide (an immuno­modu­la­tory agent) and dexa­meth­a­sone (a corticosteroid) or bor­tez­o­mib, thalido­mide and dexa­meth­a­sone alone. The pri­mary end­point is the proportion of patients that achieve a stringent Complete Response (sCR). In the second part of the study (currently ongoing), patients that achieved a response will undergo a second ran­dom­i­za­tion to either receive main­te­nance treat­ment of dara­tu­mu­mab 16 mg/kg every 8 weeks for up to 2 years versus no further treat­ment (observation). The pri­mary end­point of this part 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 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 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 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 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).^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.