Europe - GIT Verlag

Hospital Post Europe 04/08
For diseases of the respiratory
tract, inhaled delivery of drugs
carries major advantages over
other methods of administration.
For asthma and COPD,
e.g., a faster onset of action,
lower doses, and an improved
efficacy-to-safety ration have
been demonstrated. Until today,
in certain diseases available
inhalers have not been
found to be efficient. In Gramnegative
pneumonia, e.g., all
efforts to establish inhaled
therapy have failed.
However, a ground-breaking development
project of Bayer HealthCare und Nektar
Therapeutics in Gram-negative pneumonia
now suggests that co-operation between
pharmaceutical and device manufacturers
may lead to solutions which carry significant
benefits to patients as well as caregivers.
For this drug-device combination
– dedicated to antibiosis of pneumonia in
intubated and mechanically-ventilated patients
– preliminary Phase II results were
presented mid-May at the recent Congress
of the American Thoracic Society in Toronto.
They may well stimulate the market.
Nosocomial infections of the lung are
a major cause for disease and fatalities in
hospitals around the globe. Gram-negative
bacteria account for a substantial proportion,
if not the majority of pneumonias in
intensive care units, with a mortality risk as
high as 50 % in mechanically-ventilated patients,
underlined Prof. Donald Low, Head
of the Department of Microbiology at the
University Health Network and Mount Sinai
Hospital, Toronto. “[Mechanically-ventilated]
patients in critical care units are at
particularly high risk of developing pneumonia.
Most of them are already seriously
ill because of severe underlying diseases,”
added Prof. Michael Niederman, Chairman,
Department of Medicine, Winthrop
University Hospital, New York, and one of
the lead investigators of the Phase II study.
“Fast, Efficient, Avoiding
Resistance”
Fast and efficient treatment is considered
essential by experts – a challenge not adequately
met by intravenous therapies
which cannot always reach effective concentrations
in infected lungs at tolerable
doses. The new study data, according to
Prof. Niederman, “shows that the [new]
device successfully delivers the antibiotic
amikacin directly to the site of infection,
without reaching high systemic concentra-
PoLItIcs • MAnAGEMEnt 3
Dedicated Drug-Device Combinations: Huge Potential
Antibiosis of Gram-Negative Pneumonia in Intubated and Mechanically-Ventilated Patients
“Pharmaceuticals and technology
companies are invited to
co-operate” – editor-in-chief of
Hospital Post Europe
Continued from page 1
excellent reputation in the Arabian countries
– a fact we should profit from,” Winter
emphasizes. Besides medical and pharmaceutical
companies and research and technology
centres, well known university and
clinical departments contribute to the famous
reputation and worldwide-accepted
standing of Germany’s healthcare section.
His Excellency Ali Ahmed Bin Shakar,
Undersecretary of the UAE Minister of
Health, was convinced by the innovative
expertise and the quality of healthcare in
NRW as he recently accepted the invitation
of the federal state government to visit the
Heart and Diabetes Centre NRW in Bad
Oeynhausen, Germany. His main concern
was with the treatment of diabetes mellitus
and cardiovascular diseases – namely
cardiac surgery. As a university hospital of
the Ruhr-University of Bochum, the Heart
and Diabetes Centre NRW enjoys reputa-
Panel of presenters in Toronto: this dedicated drug-device combination
enables better outcomes and reduced cost of the therapy as a
whole. Foto: M. Reiter
tion as a national and international reference
centre for the consolidated treatment
of metabolic and cardiovascular diseases.
Known from the first implantation of the
LionHeart as an artificial heart, and the first
transplantation of a beating heart without
use of a heart and lung machine, the Clinic
for Thoracic and Cardiovascular surgery
is amongst the world leading institutions
in this field. The use of ventricular assist
devices (VAD) as a bridge to transplant is
not only clinical routine but also focus of
cardiovascular research. The development
of a fully implantable miniaturized artificial
heart which is supported by a grant of
“Med in NRW” is the actual indicative of a
highly innovative clinical research program
to overcome the lack of donor organs.
Recently, the diabetes centre initiated a
clinical study using stem cells in the treatment
of critical limb ischemia induced ul-
tions”. – In addition, exhaled air is filtered,
inhibiting distribution of the antibiotic into
the environment. Together with reduced
concomitant intravenous antibiotic therapy,
this may well help to reduce the risk
of resistance – which threatens to become
paramount, in particular regarding Pseudomonas
aeruginosa.
Innovative Drug-Device
Combination
Amikacin Inhale is a unique drug-device
combination, under development by antibiotics
specialist Bayer HealthCare in cooperation
with medical technology company
Nektar Therapeutics. It brings together a
special liquid formulation of the aminoglycoside
antibiotic amikacin – which binds
to bacterial ribosomal subunits to inhibit
cell replication – with Nektar Therapeutics’
Liquid Pulmonary Technology (LPT),
designed to deliver amikacin deep into
the infected lungs. The device consists of
a reservoir for the liquid antibiotic, a specially
designed and optimized electronic
mesh nebulizer, a control unit, and a set
of attachments that enable two modes of
use. It can be integrated into mechanical
ventilation systems and can also be used
as a handheld ‘off-vent’ device for patients
no longer requiring breathing assistance.
This allows for a unique full course of drug
Cooperation Across Continents
cers in patients with diabetes mellitus. The
very promising results led to the establishment
of this treatment for patients with no
option of clinical or surgical intervention.
This program is added to the highly innovative
treatment regiments of patients with
diabetic foot syndrome.
Not only as a healthcare unit is the Heart
and Diabetes Centre NRW known worldwide.
Current research projects from the
diabetes centre as well as from the cardiac
research laboratories focus on cardiovascular
diseases. The metabolic circumstances
leading to cardiac failure are of major
concern. The impact of diabetes mellitus
to the development of cardiomyopathy
(“diabetic cardiomyopathy”) is not fully
understood. Multidisciplinary research
efforts are undertaken to enlighten the
interrelation of Diabetes mellitus and cardiac
disease. The role of advanced glyca-
therapy in critically ill patients with Gramnegative
pneumonia. In order to ensure
that the delivery of amikacin occurs at the
most appropriate time, which is during inhalation,
the nebulization is triggered by
the patient’s individual breathing rhythm.
Preliminary Phase II Results
In the current study for the adjunctive treatment
of Gram-negative pneumonia in intubated
and mechanically-ventilated patients,
the combination achieved over 1,000 times
greater lung exposure to the antibiotic amikacin
as compared to intravenous route of
administration. Both the once- and twicedaily
regimens were associated with reductions
in overall antibiotic use compared to
placebo. ”This shows,” said Philip Blake,
President and CEO, Bayer Inc. Canada,
“that targeting antibiotic therapy to the site
of infection might offer superior bacterial
eradication and increased efficacy, which
in turn may result in a higher likelihood of
the patient’s survival.” Greater efficacy also
suggests positive effects on the cost of the
therapy – conventional injection therapies
Amikacin Inhale
Amikacin Inhale is a developmental name for a drug-device combination
product currently under development as an adjunctive treatment of Gramnegative
pneumonia in intubated and mechanically-ventilated patients. It
is being developed by Bayer Healthcare in cooperation with nektar therapeutics
and combines nektar therapeutics’ LPt (Liquid Pulmonary technology)
pulmonary drug delivery system with the antibiotic amikacin that has
been formulated for highly efficient aerosolised delivery to the lungs.
tion end products and protein glycation in
the progression of arteriosclerosis as well
as structural impacts on heart function are
evaluated both in clinical studies and the
research laboratory of the diabetes centre.
In an interdisciplinary approach scientists
and medicines are working together to understand
basic mechanisms and to develop
new therapeutic options.
H.E. Bin Shakar was impressed by the
interaction of the clinics for cardiology,
cardiovascular surgery and the diabetes
centre. In the UAE every fifth inhabitant is
affected by diabetes mellitus, which brings
about a strong need for a concerted treatment
of patients, both from the metabolic
as well as from the cardiac point of care.
Therefore, H.E. Dr. Ali Ahmed Bin Shakar
proposed the establishment of a similar
configured centre in the UAE. Both parties
agreed to implement a close collaboration
of ventilated patients currently cost up to
CAN-$150.000, said Prof. Low.
Phase III studies will follow. They aim is
to assess whether the addition of Amikacin
Inhale to the current standard of care recommended
by the American Thoracic Society
is more effective than aerosolized placebo
for the treatment of Gram-negative
pneumonia in intubated and mechanicallyventilated
patients.
“We Need more Collaboration
of the Kind”
Better outcome, and reduced cost – these
highly promising expected benefits were addressed
by the experts at the media round
table. “The design and development of such
dedicated drug-device combinations carries
an enormous potential for many areas,” underlined
Prof. Niederman at the ATS congress.
“Only few companies have endeavoured such
a collaboration. Amikacin Inhale is a pioneer
project; we physicians see a huge demand for
more of such collaborative solutions.”
Michael Reiter
very soon. The contractual documents
are currently prepared and H.E. Shakar is
awaited for Medica in November for the final
signature. Arab Health in January 2009
in Dubai will be an optimum time point to
advance the collaboration by evaluating
further steps.
Contact:
Bernd Stratmann, PhD
Research Director
Heart and Diabetes Centre North
Rhine Westphalia
Bad Oeynhausen, Germany
Tel.: + 49 5731/973768
bstratmann@hdz-nrw.de
www.hdz-nrw.de