Crucell 2008 Combating Infectious Diseases

28 Our Business
Research & Development
Our Business 29
Research & Development
Resistance of influenza (H1N1) against oseltamivir is almost universal
1 98% United States
2 13-82% South America
(6 countries)
3 97% European Union
4 45% Russian Federation
5 93% Japan
6 91% Philippines
7 10o% South Africa
8 94% Australia
9 31% Southern
hemisphere
(16 countries)
Source: WHO, January 2009.
1
2
3
7
9
4
6
5
8
Crucell’s
monoclonal
antibodies against
influenza strongly
outperform
oseltamivir in
pre-clinical trials.
Rabies causes over 50,000 deaths each year in endemic countries
Africa 24,000
India 20,000
China 2,500 and up
Other Asia 8,900
Source: FX Meslin, WHO
NECTM, KNobel and
Tang et al EID, 2005;
Zhang et al InFoRab
2005, APCRI data.
In Asia and Africa,
where an estimated
40,000 to 70,000
people die from
rabies each year,
there is a significant
unmet medical
need for a safe,
effective and
affordable
treatment.
Antibodies
Antibodies are proteins made naturally by cells
of the body’s immune system. They function as
one of the body’s principal defense mechanisms
against pathogens, which are disease causing agents
such as parasites, viruses or bacteria. Antibodies
recognize and bind to invading pathogens, ultimately
eliminating them, thus playing a crucial role in
protecting humans against disease.
Influenza antibodies H1N1 and H5N1
There is a growing fear within the medical
community concerning the potential reoccurrence
of a pandemic influenza outbreak, similar to the
1918 ‘Spanish flu’ pandemic. A pandemic can start
when a new influenza virus subtype emerges that
meets three conditions: it infects humans causing
serious illness; it spreads easily; and there is
sustained human-to-human transmission of
the virus.
Crucell has discovered the first human monoclonal
antibodies for the prevention and treatment of the
‘bird flu’ strain H5N1, as well as H1N1, which is similar
to the strain responsible for the devastating
pandemic in 1918. The antibodies provide immediate
protection and neutralize a broad range of H5N1
and H1N1 strains in pre-clinical models. In December
2008, Crucell presented data showing that the
mAb CR6261 was 100% successful in preventing
infection with H5N1. When given after H5N1
infection, Crucell’s mAb demonstrated the ability to
prevent death and cure disease in all cases. The mAb
also performed significantly better than the antiinfluenza
drug oseltamivir for the prevention and
treatment of H1N1 infection, illustrating the
potential use for seasonal applications as well.
This is especially important as the resistance of
influenza strains for oseltamivir is rapidly increasing.
Rabies Antibody Combination
Globally, around 10 million people a year are treated
after exposure to rabies virus. Nevertheless, between
40,000 and 70,000 people die of rabies each year,
mainly in Africa, China and India. This highlights
the significant unmet medical need for a safe,
effective and affordable rabies treatment. The
approach currently used to prevent symptomatic
disease and death in people exposed to rabies virus
combines immunoglobulins (antibodies prepared
from human or equine blood) with the vaccine.
Concerns about the safety and availability of bloodderived
rabies antibodies have prompted the search
for alternatives.
Using MAbstract ® and PER.C6 ® technology,
Crucell scientists in collaboration with the
Thomas Jefferson University in Philadelphia and
the US Centers for Disease Control and Prevention
in Atlanta have discovered a combination of human
monoclonal antibodies (mAbs) for the postexposure
treatment of rabies. Clinical testing of this
mAb combination made good progress during 2008,
leading to the presentation in October of very
promising efficacy and safety data from a Phase II
trial in the USA. In order to test the mAb
combination in different populations and settings,
additional Phase II trials were started in May 2008
(among children in the Philippines) and February
2009 (among adults in India).
Since January 2008, the route towards global
availability of this next-generation, life-saving rabies
biological is being facilitated by Crucell’s strategic
partnership with sanofi pasteur, a world leader
in rabies immunization. The US Food and Drug
Administration (FDA) has granted Crucell’s mAb
combination Fast Track status, which paves the
way for priority handling of the regulatory dossier.
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