Genmab Announces Submission of Supplemental New Drug Application
for Daratumumab in Front Line Multiple Myeloma in Japan
Company Announcement
- Supplemental new drug application submitted in Japan
for daratumumab in combination with bortezomib, melphalan and
prednisone for the treatment of patients with newly diagnosed
multiple myeloma ineligible for autologous stem cell
transplant
- Submission based on data from Phase III ALCYONE
study
- Genmab to receive USD 2 million milestone payment from
Janssen
Copenhagen, Denmark; December 14, 2018 –
Genmab A/S (Nasdaq Copenhagen: GEN) announced today that
Janssen Pharmaceutical K.K. has submitted a supplemental new drug
application (sNDA) to the Ministry of Health, Labor and Welfare
(MHLW) in Japan, for the use of daratumumab (DARZALEX®) 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 (ASCT).
The application will receive a priority review. The
submission of the application triggers a milestone payment of USD 2
million to Genmab from Janssen. In February 2018, the MHLW granted
Orphan Drug Designation to DARZALEX for patients with newly
diagnosed multiple myeloma. In August 2012, Genmab granted Janssen
an exclusive worldwide license to develop, manufacture and
commercialize daratumumab.
“We are extremely pleased that daratumumab in front line
multiple myeloma has now been submitted in Japan. Should this
submission be approved, it would bring an exciting new therapeutic
option to Japanese multiple myeloma patients in need,” said Jan van
de Winkel, Ph.D., Chief Executive Officer of Genmab.
The submission was based on data from the Phase III ALCYONE
study that showed a reduction of the risk of disease progression or
death by 50 percent in newly diagnosed ASCT ineligible multiple
myeloma patients when daratumumab is combined with bortezomib,
melphalan and prednisone. This data was presented as a
Late-Breaking Abstract at the 2017 American Society of Hematology
(ASH) Annual Meeting and published in The New England Journal of
Medicine in December, 2017.
About the ALCYONE studyThis Phase III study
(NCT02195479) is a randomized, open-label, multicenter study and
includes 706 newly diagnosed patients with multiple myeloma who are
ineligible for ASCT. Patients were randomized to receive 9 cycles
of either VMP [bortezomib (a proteasome inhibitor), melphalan (an
alkylating chemotherapeutic agent) and prednisone (a
corticosteroid)] combined with daratumumab, or VMP alone. In the
daratumumab treatment arm, patients received 16 mg/kg of
daratumumab once weekly for six weeks (cycle 1; 1 cycle = 42 days),
once every three weeks from cycles 2 to 9, once every 4 weeks from
cycle 9 until disease progression. The primary endpoint of
the study is progression free survival (PFS).
About multiple myelomaMultiple 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 Japan, after
leukemia and lymphoma.2 Approximately 8,200 new patients were
projected to be diagnosed with multiple myeloma and approximately
4,200 people were projected to die from the disease in Japan in
2017.2 Globally, it was estimated that 124,225 people would be
diagnosed and 87,084 would die from the disease in 2015.3
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.4 Patients who relapse after treatment with standard
therapies, including proteasome inhibitors or immunomodulatory
agents, have poor prognoses and few treatment options.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 (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.Contact:
Rachel Curtis Gravesen, Senior Vice President, Investor Relations
& CommunicationsT: +45 33 44 77 20; E: rcg@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.
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 Cancer Information Service. “Projected Cancer
Statistics 2017.” Available at
http://ganjoho.jp/en/public/statistics/short_pred.html. Accessed
February 2018..3 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. 4 American Cancer Society. "How is
Multiple Myeloma Diagnosed?"
http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis.
Accessed June 2016.5 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. 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.
Company Announcement no. 36CVR no. 2102 3884LEI Code
529900MTJPDPE4MHJ122
Genmab A/SKalvebod Brygge 431560 Copenhagen VDenmark
- 181214_36_CA_Japan VMP Submission