• First part of regu­la­tory package submitted to the U.S. FDA for label expansion of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for patients with newly diag­nosed multiple myeloma who are not can­di­dates for high dose chemo­ther­apy and au­tol­o­gous stem cell trans­plant
• The U.S. FDA plan to review the sub­mission under their Real-Time Oncology Review Pilot Program
• Application based on data from Phase III MAIA (MMY3008) study

Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq Copenhagen: GEN) announced today that its licensing partner, Janssen Biotech, Inc. (Janssen), has submitted the first part of a regu­la­tory sub­mission to the U.S. Food and Drug Admin­istra­tion (U.S. FDA) for a label expansion to in­clude the use of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients with newly diag­nosed multiple myeloma who are not can­di­dates for high dose chemo­ther­apy and au­tol­o­gous stem cell trans­plant (ASCT).  The U.S. FDA plans to review this appli­ca­tion under their Real-Time Oncology Review (RTOR) pilot pro­gram. Inclusion in the RTOR pilot pro­gram does not guar­an­tee or in­­crease the probability of approval of this supple­mental Biologics License Appli­ca­tion (sBLA). In August 2012, Genmab granted Janssen an exclusive world­wide license to develop, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab.

“We are en­cour­aged that the sub­mission for dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone has begun, with a poten­tial for the regi­men to be approved earlier for US patients,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The sub­mission package is based on data from the Phase III MAIA (MMY3008) study of dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone as treat­ment for patients with newly diag­nosed multiple myeloma, who are not can­di­dates for high dose chemo­ther­apy and ASCT.

About the RTOR Pilot Program

The aim of the RTOR pilot pro­gram is to explore a more efficient review process for supple­mental New Drug Applications (sNDAs) and sBLAs to provide safe and effective treat­ments to patients as early as possible. More in­for­ma­tion is avail­able on the U.S. FDA website (link). 

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 was 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 treat­ment with lena­lido­mide and dexa­meth­a­sone until disease pro­gres­sion or unacceptable toxicity. The pri­mary end­point of the study is pro­gres­sion free survival.

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 the treat­ment of adults with re­lapsed or refractory multiple myeloma.  DARZALEX is the first human CD38 mono­clonal anti­body to reach the mar­ket in the United Stated, Europe and Japan.  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, 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.

Cautions Concerning Forward-Looking Statements

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.