Company Announcement
- Arzerra approved for use in EU as first-line treatment
for CLL in combination with chlorambucil or bendamustine for
patients ineligible for fludarabine-based therapy
- Approval based on Phase III data from study with
ofatumumab + chlorambucil & Phase II data from study with
ofatumumab and bendamustine
GlaxoSmithKline plc (LSE:GSK) and Genmab
A/S (Copenhagen:GEN) announced today that the
European Commission (EC) has granted marketing authorization for a
new indication for the use of Arzerra
(tm) (ofatumumab), a human monoclonal
antibody against CD20, in combination with chlorambucil or
bendamustine for the treatment of patients with chronic lymphocytic
leukemia (CLL) who have not received prior therapy and who are not
eligible for fludarabine-based therapy.1
"Today's decision by the European Commission for the first-line
use of Arzerra offers a new treatment option for appropriate CLL
patients and enables physicians flexibility in their choice of
adjunct chemotherapy - chlorambucil or bendamustine," said Dr.
Paolo Paoletti, President of Oncology, GSK.
"We are very pleased to receive this decision that Arzerra is
approved in the EU in the front-line setting in combination with
two different alkylating chemotherapies. This is another important
milestone and we look forward to a successful launch under this new
indication of the drug in Europe in the coming months. We hope to
receive additional approvals in frontline across the globe in the
future,"said Jan van de Winkel, Ph.D., Chief Executive Officer of
Genmab.
The EC authorization of the first-line indication for Arzerra
(ofatumumab) is based on results from two trials1:
- A randomized, Phase III open-label, parallel-arm, multicenter,
pivotal study (OMB110911, COMPLEMENT 1) evaluating the combination
of ofatumumab and chlorambucil (N=221) versus chlorambucil alone
(N=226) in CLL patients for whom fludarabine-based treatment is
considered inappropriate. In this study, treatment with ofatumumab
and chlorambucil demonstrated a statistically significant, 71 per
cent improvement in median progression-free survival (PFS) compared
to chlorambucil alone (22.4 months versus 13.1 months,
respectively) (HR=0.57 [95 per cent CI, 0.45, 0.72]
p<0.001).1
- A single-arm, multicenter, Phase II study (OMB115991)
evaluating ofatumumab in combination with bendamustine in 44
patients with previously untreated CLL for whom fludarabine-based
treatment was considered inappropriate. Results of this study
demonstrated that ofatumumab in combination with bendamustine
provided an overall response rate (ORR)of 95 per cent [95 per cent
CI, 85, 99] and a complete response rate (CR) of 43 per cent.1
Safety information for Arzerra (ofatumumab)
The overall safety profile of ofatumumab in CLL (previously
untreated and relapsed or refractory) is based on data from 511
patients in clinical trials. This includes 250 patients with
relapsed or refractory CLL who were treated with ofatumumab alone
and 261 patients with previously untreated CLL for whom
fludarabine-based therapy was considered inappropriate and who were
treated in combination with an alkylating agent.
The most common undesirable effects for ofatumumab include
adverse events associated with infusion reactions, cytopenias
(neutropenia, anemia, febrile neutropenia, thrombocytopenia,
leukopenia) and infections (lower respiratory tract infection,
including pneumonia, upper respiratory tract infection, sepsis,
including neutropenic sepsis and septic shock, herpes virus
infection, urinary tract infection).1
Contraindications:
Hypersensitivity to ofatumumab or to any of the excipients.1
Special warnings and precautions for use of ofatumumab
are summarized as follows:
Infusion reactions1
Ofatumumab has been associated with infusion reactions leading
to temporary interruption of treatment or withdrawal of treatment.
Infusion reactions may include anaphylactoid events, cardiac
events, chills/rigors, cough, cytokine release syndrome, diarrhea,
dyspnea, fatigue, flushing, hypertension, hypotension, nausea,
pain, pyrexia, rash, and urticaria. Infusion reactions occur
more frequently on the first day of infusion and tend to decrease
with subsequent infusions. Patients with a history of
decreased pulmonary function may be at a greater risk for pulmonary
complications from severe reactions.
Tumor lysis syndrome1
In patients with CLL, tumor lysis syndrome (TLS) may occur with
use of ofatumumab. Risk factors for TLS include a high tumor
burden, high concentrations of circulating cells
(>= 25,000/mm3), hypovolemia, renal insufficiency, elevated
pre-treatment uric acid levels and elevated lactate dehydrogenase
levels. Management of TLS includes correction of electrolyte
abnormalities, monitoring of renal function, maintenance of fluid
balance and supportive care.
Progressive multifocal leukoencephalopathy1
Progressive multifocal leukoencephalopathy (PML) and death has
been reported in CLL patients receiving cytotoxic pharmacotherapy,
including ofatumumab. If a diagnosis of PML is suspected
ofatumumab should be discontinued and referral to a neurologist
should be considered.
Immunizations1
The safety of, and ability to generate a primary or anamnestic
response to, immunization with live attenuated or inactivated
vaccines during treatment with ofatumumab has not been
studied.
Hepatitis B1
Hepatitis B virus (HBV) infection and reactivation, in some
cases resulting in fulminant hepatitis, hepatic failure and death,
has occurred in patients treated with drugs classified as
CD20-directed cytolytic antibodies, including ofatumumab. All
patients should be screened for HBV infection before initiation of
ofatumumab treatment, patients previously exposed to HBV should be
followed closely in consultation with an expert in this
disease. Patients with evidence of prior HBV infection should
be monitored for clinical and laboratory signs of hepatitis or HBV
reactivation.
Cardiovascular1
Patients with a history of cardiac disease should be monitored
closely. Ofatumumab should be discontinued in patients who
experience serious or life-threatening cardiac arrhythmias.
The effect of multiple doses of ofatumumab on the QTc interval
was evaluated in a pooled analysis of three open-label studies in
patients with CLL (N=85). Increases above 5 msec were observed
in the median/mean QT/QTc intervals in the pooled analysis.
No large changes in the mean QTc interval (i.e., >20
milliseconds) were detected.
Bowel obstruction1
Bowel obstruction has been reported in patients receiving
anti-CD20 monoclonal antibody therapy, including ofatumumab.
Patients who present with abdominal pain, especially early in the
course of ofatumumab therapy, should be evaluated and appropriate
treatment instituted.
Please consult the full Summary of Product Characteristics for
all the labeled safety information for Arzerra.
About CLL
CLL, the most commonly diagnosed adult leukemia in Western
countries,2,3 accounts for approximately one-third of all cases of
leukemia.4 In Europe, the incidence rate for all subtypes of
leukemia is 7.2 per 100,000 of which 34 per cent of cases are CLL,
translating to approximately 12,500 new CLL cases each year.5,6,7
Each year, CLL is responsible for approximately 6,000 deaths
across Europe.5,6,7 The average age of diagnosis is 72 years old,4
and approximately 90 per cent of patients with CLL are estimated to
be over the age of 55.8The majority of patients with CLL have at
least one significant comorbidity such as hypertension, diabetes,
cardiovascular disease, or chronic obstructive pulmonary disease
(COPD).9
About ofatumumab
Arzerra (ofatumumab) is a monoclonal antibody that is designed
to target the CD20 molecule found on the surface of CLL cells and
normal B lymphocytes.1
Ofatumumab is also authorized in the EU for the treatment of
patients with CLL refractory to fludarabine and alemtuzumab.
Ofatumumab is being developed under a co-development and
collaboration agreement between Genmab and GSK.
Arzerra is a trademark of the GSK group of companies.
GSK - one of the world's leading research-based
pharmaceutical and healthcare companies - is committed to improving
the quality of human life by enabling people to do more, feel
better and live longer. For further information please visit
www.gsk.com.
About Genmab A/S Genmab is a publicly traded,
international biotechnology company specializing in the creation
and development of differentiated human antibody therapeutics for
the treatment of cancer. Founded in 1999, the company
currently has one marketed antibody, Arzerra(r) (ofatumumab) for
the treatment of certain chronic lymphocytic leukemia indications,
a clinical pipeline with both late and early stage programs, and an
innovative pre-clinical 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(tm) platform which creates effector
function enhanced antibodies. Genmab's deep antibody expertise is
expected to provide a stream of future product candidates.
Partnering of selected innovative product candidates and
technologies is a key focus of Genmab's strategy and the company
has alliances with top tier pharmaceutical and biotechnology
companies. For more information visit www.genmab.com.
GSK
enquiries:
UK Media
enquiries: David
Mawdsley +44
(0) 20 8047
5502
(London)
Simon
Steel +44
(0) 20 8047
5502
(London)
David
Daley +44
(0) 20 8047
5502
(London)
Catherine
Hartley +44
(0) 20 8047
5502
(London)
Sarah
Spencer +44
(0) 20 8047
5502
(London)
US Media
enquiries:
Stephen
Rea
+1 215 751
4394
(Philadelphia)
Melinda
Stubbee
+1 919 483
2510
(North Carolina)
Mary
Anne
Rhyne
+1 919 483
0492
(North Carolina)
Sarah
Alspach
+1 202 715
1048
(Washington)
Jennifer
Armstrong
+1 215 751
5664
(Philadelphia)
Analyst/Investor
enquiries:
Ziba
Shamsi
+44 (0) 20 8047
5543
(London)
Kirsty Collins (SRI &
CG) +44 (0) 20 8047
5534
(London)
Tom
Curry
+ 1 215 751
5419 (Philadelphia)
Gary
Davies +44
(0) 20 8047
5503
(London)
James
Dodwell
+44 (0) 20 8047
2406
(London)
Jeff
McLaughlin
+1 215 751
7002 (Philadelphia)
Lucy
Singah
+44 (0) 20 8047
2248
(London)
Genmab enquiries:
Rachel Curtis
Gravesen
T: +45 33 44 77 20
M: +45 25 12 62 60
E: r.gravesen@genmab.com
Forward Looking Statement for Genmab 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); the DuoBody logo(tm); the
Hexabody logo(tm); HuMax(r); HuMax-CD20(r); DuoBody(r), HexaBodyTM
and UniBody(r).
Cautionary statement regarding forward-looking
statements GSK cautions investors that any forward-looking
statements or projections made by GSK, including those made in this
announcement, are subject to risks and uncertainties that may cause
actual results to differ materially from those projected. Such
factors include, but are not limited to, those described under Item
3.D 'Risk factors' in the company's Annual Report on Form 20-F for
2013.
Registered in England & Wales:
No. 3888792
Registered Office:
980 Great West Road
Brentford, Middlesex
TW8 9GS
References
- GlaxoSmithKline. ARZERRA Summary of Product Characteristics
2014.
- Wadhwa P, Morrison VA. Infectious complications of chronic
lymphocytic leukemia. Seminars in Oncology. 2006;33:240-249.
http://www.cllsupport.org.uk/infections.pdf. Accessed 27 May
2014.
- Leukemia & Lymphoma Society. Chronic Lymphocytic Leukemia.
http://www.lls.org/#/diseaseinformation/leukemia/chroniclymphocyticleukemia/.
Accessed 27 May 2014.
- American Cancer Society. What are the key statistics for
chronic lymphocytic leukemia?
http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-key-statistics.
Accessed 27 May 2014.
- Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers
C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.0,
Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11
[Internet]. Lyon, France: International Agency for Research on
Cancer; 2013. http://globocan.iarc.fr. Accessed 3 June 2014.
- United Nations. World Population Prospects, 2012 Revision.
Population Division of the Department of Economic and Social
Affairs, United Nations. http://esa.un.org/unpd/wpp/. Accessed
February 2014.
- Watson L, Wyld P, Catovsky D. Disease burden of chronic
lymphocytic leukaemia within the European Union. Eur J Haematol
2008;81:253-258.
- Eichhorst B, Hallek M, Dreyling M. Chronic lymphocytic
leukemia: ESMO clinical recommendations for diagnosis, treatment
and follow-up. Ann Oncol. 2011;22 Suppl 2, 50-54.
http://annonc.oxfordjournals.org/content/22/suppl_6/vi50.full.
Accessed 27 May 2014.
- Shanafelt, TD, et al. Quality of life in chronic lymphocytic
leukemia: an international survey of 1482 patients. British Journal
of Hematology. 2007;139, 255-264.
Company Announcement no. 33 CVR no. 2102 3884
Genmab A/S Bredgade 34E 1260 Copenhagen K Denmark
Genmab A S (PK) (USOTC:GNMSF)
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