• Phase III POLLUX study of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone in patients with re­lapsed or refractory multiple myeloma met the pri­mary end­point at a pre-planned interim analysis
• Independent Data Monitoring Committee rec­om­mends unblinding the data
• Data will be discussed with health author­i­ties to prepare for regu­la­tory filings

{{image}}Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq Copenhagen: GEN) announced today that the Phase III POLLUX study (MMY3003) of dara­tu­mu­mab in combi­na­tion with lena­lido­mide and dexa­meth­a­sone versus lena­lido­mide and dexa­meth­a­sone in patients with re­lapsed or refractory multiple myeloma met the pri­mary end­point of im­prov­ing pro­gres­sion free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR) = 0.37 (95% CI 0.27-0.52), p < 0.0001). Patients who received treat­ment with dara­tumu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone had a 63% reduction in risk of their disease progressing, com­pared to those who did not receive dara­tumu­mab. The median PFS for patients treated with dara­tu­mu­mab in combi­na­tion with lena­lido­mide and dexa­meth­a­sone has not been reached, com­pared to an esti­mated median PFS of 18.4 months for patients who received lena­lido­mide and dexa­meth­a­sone alone.

Overall, the safety profile of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone was man­age­able and con­sis­tent with the known safety profile of the lena­lido­mide and dexa­meth­a­sone combi­na­tion, with the ongoing Phase II study, GEN503, which eval­u­ated safety and efficacy of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone as well as dara­tu­mu­mab mono­therapy.

Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was rec­om­mended that the data be unblinded. Patients originally assigned to the lena­lido­mide plus dexa­meth­a­sone alone treat­ment group will be offered the option of receiving dara­tu­mu­mab mono­therapy fol­low­ing con­firmed disease pro­gres­sion. All patients will con­tinue to be monitored for safety and over­all survival. Further analysis of the safety and efficacy data is underway and will be shared with the health author­i­ties. Janssen Biotech, Inc., which licensed dara­tu­mu­mab from Genmab in 2012, will engage in a dialogue with health author­i­ties about the poten­tial for a regu­la­tory sub­mission for this indi­ca­tion. The trial results are also aimed to be presented at the 21st Congress of the European Hematology Associa­tion (EHA) as well as submitted for publication in a peer-reviewed journal.

“The POLLUX study is the second key Phase III study of dara­tu­mu­mab to meet the pri­mary end­point at a pre-planned interim analysis and dem­onstrates a favorable benefit-risk ratio. We have now seen that dara­tu­mu­mab can poten­tially be used to effectively treat re­lapsed or refractory multiple myeloma in combi­na­tion with either lena­lido­mide or bor­tez­o­mib, two standard of care multiple myeloma treat­ments,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the study

The Phase III POLLUX study enrolled 569 patients who had re­lapsed or refractory multiple myeloma. Patients were ran­domized to receive either dara­tu­mu­mab com­bined with lena­lido­mide (an immuno­modu­la­tory drug) and dexa­meth­a­sone (a corticosteroid), or lena­lido­mide and dexa­meth­a­sone alone. 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 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lym­phoma.² 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 2015.³ 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. 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)⁷, 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

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 February 2016.
2. National Cancer Institute. "A Snapshot of Myeloma." Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed February 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 September 2015.
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 September 2015.
5. American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed February 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 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: 311-321.
10. Khagi, Y and Mark, TM. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther. 2014; 7: 1095–1100

Source: Genmab.