• DARZALEX approved in Europe in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone in patients with newly diag­nosed multiple myeloma
• Approval follows pos­i­tive opinion by European Committee for Medicinal Products for Human Use (CHMP) in July
• Genmab to receive mile­stone pay­ment of USD 13 million from Janssen upon first sale of DARZALEX in the newly approved indi­ca­tion

Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq Copenhagen: GEN) announced today that the European Com­mis­sion (EC) has granted mar­ket­ing authori­za­tion for DARZALEX^® (dara­tu­mu­mab) in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone (VMP), for the treat­ment of 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 July 2018. In August 2012, Genmab granted Janssen Biotech, Inc. (Janssen) an exclusive world­wide license to develop, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab.

Genmab will receive a mile­stone pay­ment of USD 13 million from Janssen in connection with the first commercial sales of DARZALEX under the expanded label. The sales are ex­pec­ted to occur quickly after the approval. This mile­stone pay­ment was in­cluded in the financial guidance issued by Genmab originally on February 21, 2018 and then reiterated in sub­se­quent quarterly financial reports, most recently on August 8, 2018, and as such there is no change to the com­pany’s financial guidance fol­low­ing this approval.

“Approved in this indi­ca­tion in the U.S. since early May, DARZALEX in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone will now be­come an option for newly diag­nosed multiple myeloma patients in Europe,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “We are very pleased that many more patients in need will have the oppor­tu­ni­ty for treat­ment with this regi­men and we look for­ward to seeing this com­bi­na­tion launched in Europe.”

The pos­i­tive opinion of the CHMP was based on data from the Phase III ALCYONE (MMY3007) 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 Approximately 35,433 new patients were diag­nosed with multiple myeloma and approx­i­mately 22,060 people died from the disease in Western Europe in 2016.³ Globally, it was esti­mated that 138,509 people were diag­nosed and 98,437 died from the disease in 2016.³  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) 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 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 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).^5,6,7,8,9

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.  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 and other blood cancers.  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. Cowan AJ, Allen C, Barac A, et al. Global burden of multiple myeloma: a systematic analysis for the Global Burden of Disease Study 2016. JAMA Oncology. Published online May 16, 2018. doi:10.1001/jamaoncol.2018.2128
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, May 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761036s013lbl.pdf Last accessed May 2018
6. 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.
7. 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.
8. 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.
9. 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.