• DARZALEX (dara­tu­mu­mab) receives European con­di­tional mar­ket­ing authori­za­tion for heavily pre-treated or double refractory multiple myeloma
• First CD38 mono­clonal anti­body approved in Europe

Copenhagen, Denmark; May 23, 2016 – Genmab A/S (Nasdaq Copenhagen: GEN) announced today that the European Com­mis­sion (EC) has granted a con­di­tional mar­ket­ing authori­za­tion for first-in-class CD38 anti­body DARZALEX® (dara­tu­mu­mab). The con­di­tional approval is for the use of DARZALEX® as mono­therapy for the treat­ment of adult patients with re­lapsed and refractory multiple myeloma, whose prior ther­apy in­cluded a pro­te­a­some inhibitor (PI) and an immuno­modu­la­tory agent and who have dem­onstrated disease pro­gres­sion on the last ther­apy. The EC approval follows a pos­i­tive opinion issued for DARZALEX by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in April 2016. Conditional mar­ket­ing authori­za­tions are granted by the EMA for med­i­cines where the benefit of im­medi­ate avail­a­bil­ity outweighs the risk of less com­pre­hen­sive data than nor­mally required. Continued approval for this indi­ca­tion may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in con­firmatory trials.

DARZALEX is the first human CD38 mono­clonal anti­body (mAb) approved in Europe. The European approval follows the November 2015 U.S. Food and Drug Admin­istra­tion (FDA) approval of DARZALEX 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. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive world­wide license to develop, manu­fac­ture and com­mer­cial­ize DARZALEX.

The mar­ket­ing authori­za­tion was based on data from the Phase II study (SIRIUS MMY2002, published in The Lancet in January 2016), the Phase I/II GEN501 mono­therapy study (published in The New England Journal of Medicine in August 2015) and data from three addi­tional sup­port­ive studies. These studies in­cluded heavily pre-treated patients with re­lapsed and refractory multiple myeloma who had exhausted other approved treat­ment options and whose disease was progressive at enrolment. Findings from a com­bined efficacy analysis of the GEN501 and MMY2002 (SIRIUS) trials dem­onstrated that after a mean follow-up of 14.8 months, the esti­mated median over­all survival (OS) for single-agent dara­tu­mu­mab (16 mg/kg) in these heavily pre-treated patients was 20 months (95 per­cent Confidence Interval, 15 months to not yet estimable). The over­all response rate (ORR) for the com­bined analysis was 31 per­cent, and 83 per­cent of patients achieved stable disease or better.¹

“At Genmab we are driven by a desire to im­prove the quality of life for cancer patients and their families. The approval of the mar­ket­ing appli­ca­tion for DARZALEX provides the oppor­tu­ni­ty to do just that for multiple myeloma patients living in the EU and rep­re­sents a landmark event for these patients and their families, as well as for Genmab and Janssen,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Daratumumab dem­onstrated a clin­i­cally man­ageable safety profile. The most commonly occurring adverse reac­tions (in 20 per­cent or more of patients in three pooled clin­i­cal studies) were in­fusion-related reac­tions (IRRs), fatigue, pyrexia, cough, nausea, back pain, upper res­pira­tory tract in­fec­tion, anemia, neu­tro­penia (abnormally low levels of neu­tro­phils, a type of white blood cell) and thrombo­cytopenia (abnormally low levels of platelets in the blood).²

In data from three pooled clin­i­cal studies in­­clud­ing a total of 156 patients, four per­cent of patients dis­con­tinued treat­ment due to adverse reac­tions, none of which were con­sidered drug-related. IRRs were reported in approx­i­mately half of all patients treated with DARZALEX, the majority of which (91 per­cent) occurred during the first in­fusion. Seven per­cent of patients had an IRR at more than one in­fusion. Common (≥5 per­cent) symp­toms of IRRs in­cluded nasal congestion, chills, cough, allergic rhinitis, throat irritation, dyspnea, and nausea, and these were mild to mod­er­ate in severity.² Severe IRRs (4 per­cent), in­­clud­ing bron­cho­spasm (1.3 per­cent), hyper­tension (1.3 per­cent), and hypoxia, or de­creased oxygen supply to the tissues (0.6 per­cent), were also reported.²

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.³ Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lym­phoma.⁴ Approximately 26,850 new patients were esti­mated to be diag­nosed with multiple myeloma and approx­i­mately 11,240 people would die from the disease in the U.S. in 2015.⁵ Globally, it was esti­mated that 124,225 people would be diag­nosed and 87,084 would die from the disease in 2015.⁶ 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.⁷ Patients who relapse after treat­ment with standard ther­a­pies, in­­clud­ing pro­te­a­some inhibitors or immuno­modu­latory agents, have poor prognoses and few treat­ment options.⁸

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.² 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,^2,9 and multiple immune-mediated mech­a­nisms, in­­clud­ing complement-dependent cyto­tox­icity,^2,9 anti­body-dependent cellular phago­cytosis^10,11 and anti­body-dependent cellular cyto­tox­icity.^2,9 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.²

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. Usmani S, Weiss B, Bahlis NJ, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2015;126(23):abstract 29.
2. DARZALEX US Prescribing Information, November 2015.
3. American Cancer Society. "Multiple Myeloma Overview." Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed February 2016.
4. National Cancer Institute. "A Snapshot of Myeloma." Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed February 2016.
5. American Cancer Society. "What are the key statistics about multiple myeloma?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed September 2015.
6. 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 September 2015.
7. American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed February 2016.
8. 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.
9. 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.
10. 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.
11. Khagi, Y and Mark, TM. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther. 2014; 7: 1095–1100.

Source: Genmab.