Genmab Announces Submission of Supplemental Biologics License Application to FDA for Daratumumab in Relapsed Multiple Myeloma

Company Announcement

• sBLA submitted to U.S. FDA for daratumumab for treatment of patients with relapsed multiple myeloma
• Submission based on data from two Phase III studies, CASTOR and POLLUX
• Genmab to receive USD 15 million in milestone payments from Janssen

COPENHAGEN, Denmark, Aug. 17, 2016 (GLOBE NEWSWIRE) -- Genmab A/S (Nasdaq Copenhagen: GEN) announced today that its licensing partner, Janssen Biotech, Inc. has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for the use of daratumumab (DARZALEX(r)) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who received at least one prior therapy. In July 2016, daratumumab was granted a Breakthrough Therapy Designation (BTD) in this patient population.  The submission of the application triggers milestone payments totaling USD 15 million to Genmab from Janssen.  The milestone payments were included in Genmab's financial guidance for 2016 that was published on August 9, 2016.  In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

"We are thrilled that an application to expand the current label to include treatment of multiple myeloma patients who received at least one prior therapy has been submitted so soon after the initial FDA approval of daratumumab in November 2015.  The data from the Phase III CASTOR and POLLUX studies on which the submission is based was unprecedented, meriting a Breakthrough Therapy Designation from the FDA. We believe that if approved, daratumumab has the potential to make a substantial positive impact in the treatment of patients with multiple myeloma who have relapsed on their previous therapy," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

A request for Priority Review has been submitted by Janssen with this sBLA. The FDA will inform Janssen whether a Priority Review has been granted by calendar day 60 of their review starting today. If the FDA grants Priority Review, the review should be completed within 6 months from today.

The submission includes data from two Phase III studies: the CASTOR study of daratumumab in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma, and the POLLUX study of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma. The submission also included data from the Phase I study of daratumumab in combination with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma.  These data will also be used as the basis for a potential regulatory submission to the European Medicines Agency (EMA).

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 30,330 new patients are expected to be diagnosed with multiple myeloma and approximately 12,650 people are expected to die from the disease in the U.S. in 2016.³ 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 ^(r) (daratumumab)
DARZALEX^(r) (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.⁷DARZALEX 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,^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), 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.^7,11

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(r) (ofatumumab) for the treatment of certain chronic lymphocytic leukemia indications and DARZALEX(r) (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(r) platform for generation of bispecific antibodies, and the HexaBody(r) 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.
 

Contact:          
Rachel Curtis Gravesen, Senior Vice President, Investor Relations & Communications
T: +45 33 44 77 20; M: +45 25 12 62 60; E: r.gravesen@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^(r); the Y-shaped Genmab logo^(r); Genmab in combination with the Y-shaped Genmab logo(tm); the DuoBody logo^(r); the HexaBody logo(tm); HuMax^(r); HuMax-CD20^(r); DuoBody^(r); HexaBody^(r) and UniBody^(r). Arzerra^(r) is a trademark of Novartis AG or its affiliates. DARZALEX^(r) is a trademark of Janssen Biotech, Inc.

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 June 2016.
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 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 US 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: 311-21.
¹⁰ Khagi, Y and  Mark, TM. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther. 2014; 7: 1095-1100.
¹¹ 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.

Company Announcement no. 36
CVR no. 2102 3884

Genmab A/S
Bredgade 34E
1260 Copenhagen K
Denmark