Topline data from the ran­dom­ized Phase II GRIFFIN study in trans­plant eli­gible, newly diag­nosed patients with multiple myeloma treated with dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide, bor­tez­o­mib, and dexa­meth­a­sone met the study’s pri­mary end­point with a higher per­cent­age of stringent com­plete response in the dara­tu­mu­mab arm as com­pared with patients who received lena­lido­mide, bor­tez­o­mib, and dexa­meth­a­sone alone

Copenhagen, Denmark (Company Announcement) – Genmab A/S (Nasdaq Copenhagen: GEN) announced today that topline data from the Phase II GRIFFIN (MMY2004) study of newly diag­nosed patients with multiple myeloma eli­gible for high-dose chemo­ther­apy and au­tol­o­gous stem cell trans­plan­ta­tion (ASCT), who were treated with dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide, bor­tez­o­mib, and dexa­meth­a­sone (VRd), met its pri­mary end­point, demonstrating a higher per­cent­age of stringent com­plete responses (sCR) than patients who received VRd alone. Specifically, the topline data showed that 42.4% of patients treated with dara­tu­mu­mab in com­bi­na­tion with VRd achieved a sCR, com­pared to 32.0% of patients who received VRd alone, with an odds ratio of 1.57 (95% CI: 0.87 - 2.82, p=0.1359, exceeding the statistical sig­nif­i­cance at the pre-set 2-sided alpha level of 0.2). Secondary end­points, in­clud­ing the results of the minimal residual disease (MRD) analysis, sup­ported the pri­mary end­point favoring dara­tu­mu­mab in com­bi­na­tion with VRd.

Overall, the safety profile of dara­tu­mu­mab in com­bi­na­tion with VRd was con­sis­tent with the safety profile for each ther­apy separately, which has been reported from pre­vi­ous studies with the VRd regi­men as well as pre­vi­ous studies with dara­tu­mu­mab.

Further analysis of the safety and efficacy data is ongoing, and Janssen Biotech, Inc., which licensed dara­tu­mu­mab from Genmab in 2012, plans to submit addi­tional data for presentation at an upcoming medical conference.

“The data from the Phase II GRIFFIN trial underlines the poten­tial of dara­tu­mu­mab when used in com­bi­na­tion with VRd and sup­ports Janssen’s de­ci­sion to start the PERSEUS and CEPHEUS Phase III studies of dara­tu­mu­mab in com­bi­na­tion with VRd for certain frontline multiple myeloma indi­ca­tions,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “This data also builds on the efficacy and safety data for dara­tu­mu­mab as a frontline treat­ment for trans­plant-eligible multiple myeloma patients as seen in the CASSIOPEIA Phase III study in which newly diag­nosed patients with multiple myeloma who were can­di­dates for ASCT were treated with dara­tu­mu­mab com­bined with an immune-modulatory drug and a pro­te­a­some inhibitor.”

About the GRIFFIN (MMY2004) study

This Phase II trial (NCT02874742) is a ran­dom­ized, open label, parallel assignment study that in­cluded 223 patients with newly diag­nosed multiple myeloma who were eli­gible for high-dose chemo­ther­apy and au­tol­o­gous stem cell treat­ment. Patients were ran­dom­ized to receive either dara­tu­mu­mab plus lena­lido­mide, bor­tez­o­mib and dexa­meth­a­sone, or lena­lido­mide, bor­tez­o­mib and dexa­meth­a­sone alone. The pri­mary end­point of the study is the number of patients who achieve sCR by the end of the con­sol­i­da­tion treat­ment.

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 United States. 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, B-cell and T-cell ALL. 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 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 and the HexElect® plat­form, which combines two co-dependently acting HexaBody molecules to introduce selectivity while maximizing thera­peutic potency. 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.

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 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®; 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.Accessed March 2019
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, June 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s020lbl.pdf Last accessed June 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.