• U.S. FDA grants Priority Review to dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, or bor­tez­o­mib and dexa­meth­a­sone for re­lapsed multiple myeloma — February 17, 2017 PDUFA date
• U.S. FDA grants Standard Review to dara­tu­mu­mab in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone for re­lapsed or refractory multiple myeloma — June 17, 2017 PDUFA date

{{image}}Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq Copenhagen: GEN) announced today that the U.S. Food and Drug Admin­istra­tion (FDA) has granted Priority Review to the supple­mental Biologics License Application (sBLA) for the use of dara­tu­mu­mab (DARZALEX®) 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. The sBLA was submitted by Genmab's licensing partner, Janssen Biotech, Inc. in August 2016. Priority Review is an FDA desig­na­tion for drugs that treat a serious con­di­tion and may provide a sig­nif­i­cant im­prove­ment in safety or efficacy. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target date of February 17, 2017 to take a de­ci­sion on dara­tu­mu­mab in this indi­ca­tion. In addi­tion, the FDA has granted a Standard Review period for the use of dara­tu­mu­mab in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone for the treat­ment of patients with re­lapsed or refractory multiple myeloma who have received at least two prior ther­a­pies, with a pro­te­a­some inhibitor and an immuno­modu­la­tory agent. The PDUFA date for the com­bi­na­tion of dara­tu­mu­mab with poma­lido­mide/dexamethasone is June 17, 2017.

The FDA granted a Break­through Therapy Desig­na­tion for dara­tu­mu­mab 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 July 2016.

"People suffering from multiple myeloma always ultimately relapse after receiving treat­ment with the thera­pies avail­able today. The appli­ca­tion for dara­tu­mu­mab in com­bi­na­tion with current back­bone ther­a­pies for patients who have already received at least one type of treat­ment is a key step to­wards trying to bring new treat­ment options to patients with multiple myeloma," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The sBLA sub­mission in­cluded data from two Phase III studies: the CASTOR study of dara­tu­mu­mab in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone versus bor­tez­o­mib and dexa­meth­a­sone alone in patients with re­lapsed or refractory multiple myeloma, and the POLLUX study of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­metha­sone versus lena­lido­mide and dexa­metha­sone alone in patients with re­lapsed or refractory multiple myeloma. The sub­mission also in­cluded data from the Phase I study of dara­tu­mu­mab in com­bi­na­tion with poma­lido­mide and dexa­metha­sone in re­lapsed or refractory multiple myeloma.

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 30,330 new patients are ex­pec­ted to be diag­nosed with multiple myeloma and approx­i­mately 12,650 people are ex­pec­ted to die from the disease in the U.S. in 2016.³ 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 Patients who relapse after treat­ment with standard ther­a­pies, in­­clud­ing pro­te­a­some inhibitors or immuno­modu­la­tory agents, have poor prognoses and few treat­ment options.⁶

About DARZALEX® (dara­tu­mu­mab)

DARZALEX® (dara­tu­mu­mab) injection for in­tra­venous in­fusion is indicated in the United States for the treat­ment of patients with multiple myeloma who have received at least three prior lines of ther­apy, in­­clud­ing a pro­tea­some inhibitor (PI) and an immuno­modu­la­tory agent, or who are double-refractory to a PI and an immuno­modu­la­tory agent.⁷ DARZALEX is the first mono­clonal anti­body (mAb) to receive U.S. Food and Drug Admin­istra­tion (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use 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. 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. It is believed to induce rapid tumor cell death through pro­grammed cell death, or apop­tosis,^7,8 and multiple immune-mediated mecha­nisms, in­­clud­ing complement-dependent cyto­tox­icity,^7,8 anti­body-dependent cellular phago­cytosis^9,10 and anti­body-dependent cellular cyto­tox­icity.^7,8 In addi­tion, dara­tu­mu­mab ther­apy results in a reduction of immune-suppressive myeloid derived sup­pressor cells (MDSCs) and subsets of regu­la­tory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by in­­creases in CD4+ and CD8+ T cell numbers in both the periph­eral blood and bone marrow.^7,11

Daratumumab is being devel­oped by Janssen Biotech, Inc. under an exclusive world­wide license to develop, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab from Genmab. Five Phase III clin­i­cal studies with dara­tu­mu­mab in re­lapsed and front­line settings are cur­rently ongoing, and addi­tional studies are ongoing or planned to assess its poten­tial in other malignant and pre-malignant diseases on which CD38 is ex­pressed, such as smol­der­ing myeloma, non-Hodgkin's lym­phoma and a solid tumor.

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, Arzerra® (ofatumumab) for the treat­ment of certain chronic lym­pho­cytic leukemia indi­ca­tions and DARZALEX® (dara­tu­mu­mab) for the treat­ment of heavily pre­treated or double refractory multiple myeloma. Dara­tu­mu­mab is in clin­i­cal devel­op­ment for addi­tional multiple myeloma indi­ca­tions and for non-Hodgkin's lym­phoma. 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 in rela­tion­ to actual results, unless required by law.

Genmab A/S and its sub­sid­i­aries own the fol­low­ing trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in com­bi­na­tion with the Y-shaped Genmab logo™; the DuoBody logo®; the HexaBody logo™; HuMax®; HuMax-CD20®; DuoBody®; HexaBody® and UniBody®. Arzerra® is a trademark of Novartis AG or its affiliates. DARZALEX® is a trademark of Janssen Biotech, Inc.

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 June 2016.
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. Kumar, SK et al. Risk of progression and survival in multiple myeloma relapsing after last therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012; 26:149-57.
7. DARZALEX US Prescribing Information, November 2015.
8. 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.
9. 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.
10. Khagi, Y and Mark, TM. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther. 2014; 7: 1095—1100.
11. 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.

Source: Genmab.