• The Lancet published data from the Phase II study of dara­tu­mu­mab as a mono­therapy to treat heavily pre­treated and refractory multiple myeloma
• Updated data was presented at the American Society of Hematology Annual Meeting in December

Copenhagen (Press Release) – Genmab A/S (Nasdaq Copenhagen: GEN) announced today The Lancet has published data from the Phase II study (Sirius MMY2002) of dara­tu­mu­mab in patients with re­lapsed and refractory multiple myeloma. Patients that received 16 mg/kg of dara­tu­mu­mab had a median of five prior lines of ther­apy and 95.3% were refractory to both pro­te­a­some inhibitors (PIs) and immuno­modu­la­tory drugs, which are current standard of care treat­ments for multiple myeloma. The data showed a 29.2% over­all re­sponse rate (31 of 106), in­­clud­ing three stringent com­plete responses, ten very good partial responses, and 18 partial responses in patients treated with 16 mg/kg of dara­tu­mu­mab. The median time to response was one month among patients who responded to treat­ment. Median duration of response was 7.4 months, and median pro­gres­sion free survival was 3.7 months. The 12-month over­all survival rate was 64.8% and at a sub­se­quent cutoff, median over­all survival was 17.5 months. Dara­tu­mu­mab was well tolerated, with fatigue (40%) and anemia (33%) of any grade as the most common adverse events (AEs). No drug-related AEs led to treat­ment dis­con­tinu­a­tion.

“Data from the dara­tu­mu­mab Sirius study illustrates the sig­nif­i­cant poten­tial of dara­tu­mu­mab in patients with multiple myeloma who have undergone multiple rounds of prior treat­ment. Data from the study, now pub­lished in The Lancet, was the basis for the approval of dara­tu­mu­mab in heavily pre-treated or double refractory multiple myeloma by the U.S. FDA,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

In November 2015, the U.S. Food and Drug Admin­istra­tion (FDA) approved DARZALEX™ (dara­tu­mu­mab) injection for in­tra­venous in­fusion 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.1 A mar­ket­ing appli­ca­tion with data from the Sirius study and data from four other studies was submitted to the European Medicines Agency (EMA) by Janssen in September 2015 and was sub­se­quently granted accelerated assess­ment.

About the Study (Sirius MMY2002)

This two-part study enrolled 124 patients who have received at least three prior lines of ther­apy, in­­clud­ing both a pro­te­a­some inhibitor and an immuno­modu­la­tory agent, or who are double refractory to a pro­te­a­some inhibitor and an immuno­modu­la­tory agent. Examples of pro­te­a­some inhibitors are bor­tez­o­mib or car­filz­o­mib and examples of immuno­modu­la­tory agents are poma­lido­mide or lena­lido­mide. Part 1 defined an optimal dara­tu­mu­mab regi­men going for­ward, while part 2 was an expansion, based on the optimal regi­men de­ter­mined in Part 1. The pri­mary objective of the study was to define the optimal dose and dosing schedule, to de­ter­mine the efficacy of two treat­ment regi­mens of dara­tu­mu­mab as measured by over­all response rate (ORR), and to further char­ac­ter­ize the safety of dara­tu­mu­mab as a single agent.

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 26,850 new patients will be diag­nosed with multiple myeloma and approx­i­mately 11,240 people will die from the disease in the U.S. in 2015.³ Globally, it is esti­mated that 124,225 people will be diag­nosed and 87,084 will 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 PIs 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.10 DARZALEX is the first mono­clonal anti­body (mAb) to receive U.S. Food and Drug Admin­istra­tion (FDA) approval to treat multiple myeloma. 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,^7,10 and multiple immune-mediated mech­a­nisms, in­­clud­ing complement-dependent cyto­tox­icity,^7,10 anti­body-dependent cellular phago­cytosis^8,11 and anti­body-dependent cellular cyto­tox­icity.^7,10 In addi­tion, dara­tu­mu­mab ther­apy results in a reduction of immune-suppressive myeloid derived sup­pressor cells (MDSCs) and a subset of regu­la­tory T cells (Tregs) both of which express CD38. These reductions in MDSCs and Tregs were paralleled by in­­creases in CD4+ and CD8+ T cell numbers in both the periph­eral blood and bone marrow.¹⁰

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 and non-Hodgkin’s lym­phoma.

About Genmab

Genmab is a publicly traded, inter­na­tional bio­technology com­pany specializing in the creation and devel­op­sment 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 Media Release 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 Media Release 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 August 2015.
2. National Cancer Institute. "A Snapshot of Myeloma." Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed August 2015.
3. American Cancer Society. "What are the key statistics about multiple myeloma?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed August 2015.
4. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide. 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 August 2015.
5. American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed August 2015.
6. Kumar, SK et al. Leukemia. 2012 Jan;26:149-57.
7. De Weers et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. February 1, 2011 vol. 186: 1840-1848.
8. Khagi and Mark. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther. 2014; 7: 1095–1100.
9. Jing Yang and Qing Yi. Therapeutic monoclonal antibodies for multiple myeloma: an update and future perspectives. Am J Blood Res. 2011; 1: 22–33.
10. DARZALEX Prescribing Information, November 2015
11. Overdijk et al. Phagocytosis Is A Mechanism of Action for daratumumab. Available at https://ash.confex.com/ash/2012/webprogram/Paper51257.html. Accessed September 2015.

Source: Genmab.