• Phase III MAIA study of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone in front line multiple myeloma met the pri­mary end­point (PFS) at a pre-planned interim analysis demonstrating the superiority of DRd over Rd
• Independent Data Moni­tor­ing Committee rec­om­mends releasing the interim analysis results and to follow patients for survival and long-term safety
• Data will be discussed with health author­i­ties to prepare for regu­la­tory filings

Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq Copenhagen: GEN) announced today topline results from the Phase III MAIA study (MMY3008) of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (DRd) versus Rd alone as treat­ment for newly diag­nosed patients who are not can­di­dates for high dose chemo­ther­apy and au­tol­o­gous stem cell trans­plant (ASCT). The study met the pri­mary end­point of im­prov­ing pro­gres­sion free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR) = 0.55 (95% CI 0.43 – 0.72), p < 0.0001) resulting in a 45% reduction in the risk of pro­gres­sion or death in patients treated with DRd. The median PFS for patients treated with dara­tu­mu­mab in com­bi­na­tion with Rd has not been reached, com­pared to an esti­mated median PFS of 31.9 months for patients who received Rd alone.

Overall, the safety profile of dara­tu­mu­mab in com­bi­na­tion with Rd is con­sis­tent with both the known safety profiles of the Rd regi­men and dara­tu­mu­mab.

Based on the results at the pre-planned interim analysis conducted by an Independent Data Moni­tor­ing Committee (IDMC), it was rec­om­mended releasing the interim analysis results. Further analysis of the safety and efficacy data is ongoing and Janssen Biotech, Inc., which licensed dara­tu­mu­mab from Genmab in 2012, will discuss the poten­tial for a regu­la­tory sub­mission for this indi­ca­tion with health author­i­ties, and plans to submit the data to an upcoming medical conference and for publication in a peer-reviewed journal.

“We are highly en­cour­aged by this data as this is the fifth ran­dom­ized study showing a profound benefit when adding dara­tu­mu­mab to standard of care treat­ments in multiple myeloma, and the second showing efficacy for patients with newly diag­nosed multiple myeloma who are not eli­gible for ASCT. As such this data in­­creases our hope that dara­tu­mu­mab may one day help even more patients at the outset of treat­ment of this disease,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Today’s news does not impact Genmab’s 2018 financial guidance.

About the MAIA (MMY3008) study

The Phase III study (NCT02252172) is a ran­dom­ized, open-label, multi­center study that in­cludes 737 newly diag­nosed patients with multiple myeloma who are not can­di­dates for high dose chemo­ther­apy and ASCT. Patients were ran­dom­ized to receive either dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide (an immuno­modu­la­tory drug) and dexa­meth­a­sone (a corticosteroid) or lena­lido­mide and dexa­meth­a­sone alone. In the dara­tu­mu­mab treat­ment arm, patients received 16 milligrams per kilo­gram (mg/kg) weekly for first 8 weeks (Cycles 1 and 2), every other week for 16 weeks (Cycles 3 to 6) and then every 4 weeks (Cycle 7 and beyond) until pro­gres­sion of disease or unacceptable toxicity. Lena­lido­mide is admin­istered at 25 mg orally on days 1 through 21 of each 28-day cycle, and dexa­meth­a­sone was admin­istered at 40 mg once a week for both treat­ment arms. Participants in both treat­ment arms will con­tinue Rd until disease pro­gres­sion or unacceptable toxicity. The pri­mary end­point of the study is 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 30,770 new patients are ex­pec­ted to be diag­nosed with multiple myeloma and approx­i­mately 12,770 people are ex­pec­ted to die from the disease in the U.S. in 2018.³ 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

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.6 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 in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of adult patients with newly diag­nosed multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant; 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).^6,7,8,9,10

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, the HexaBody® plat­form, which creates effector function en­hanced anti­bodies and the HexElect™ plat­form, which combines two co-dependently acting HexaBody molecules to introduce selectivity while maximizing thera­peutic potency. 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®; DuoHexaBody™; HexElect™; 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. American Cancer Society. "What are the key statistics about multiple myeloma?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed March 2018
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. DARZALEX Prescribing information, May 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761036s013lbl.pdf Last accessed May 2018
7. 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.
8. 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.
9. 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.
10. 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.