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Bayer together with Nektar Therapeutics present preliminary Phase II data for the adjunctive treatment of pneumonia in intubated and mechanically-ventilated patients
Toronto/Berlin, May 19, 2008 - Bayer HealthCare together with Nektar
Therapeutics (NASDAQ: NKTR), today presented positive preliminary Phase II data
on their unique drug-device combination Amikacin Inhale at the American
Thoracic Society (ATS) annual meeting. Amikacin Inhale, currently being
studied for the adjunctive treatment of Gram-negative pneumonia in intubated
and mechanically-ventilated patients, achieved over 1000 times greater lung
exposure to the antibiotic amikacin as compared to intravenous route of
administration. This shows that targeting antibiotic therapy to the site of
infection might offer superior bacterial eradication and increased efficacy,
which may result in a higher likelihood of the patient's survival. Currently,
Gram-negative pneumonia carries a mortality risk as high as 50 percent in
mechanically-ventilated patients.(1)
"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," said Professor Michael Niederman,
Chairman, Department of Medicine, Winthrop University Hospital, New York, and
one of the lead investigators of the study. "Because of the high morbidity and
mortality of Gram-negative pneumonia, fast and efficient treatment is
essential. Intravenous therapies cannot always reach effective concentrations
in infected lungs at tolerable doses. The new study data shows that the device
successfully delivers the antibiotic directly to the site of infection, without
reaching high systemic concentrations."
Amikacin Inhale is a unique drug-device combination, being developed by Bayer
HealthCare in cooperation with Nektar Therapeutics, combining a special liquid
formulation of the aminoglycoside antibiotic amikacin with Nektar Therapeutics'
proprietary Liquid Pulmonary Technology (LPTTM), designed to deliver amikacin
deep into the infected lungs. The device 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 therapy in critically ill patients with Gram-negative
pneumonia. 'Gram-negative pneumonia' refers to pneumonia caused by a
laboratory-defined group of pathogens, the Gram-negative bacteria. These
account for a substantial proportion, if not the majority of pneumonias in
intensive care units (ICUs).
"A challenge in treating Gram-negative pneumonia in ICUs is that they have
grown increasingly resistant to currently available antibiotics," said
Professor Donald Low, Head of the Department of Microbiology at the Toronto
Medical Laboratories and Mount Sinai Hospital, Toronto, Canada. "A new
treatment option such as Amikacin Inhale, which fights pneumonia directly at
the site of infection, may be able to help decrease resistance - especially if
concomitant intravenous antibiotic therapy can also be reduced."
Amikacin Inhale will enter Phase III trials later this year to further assess
its efficacy and safety in mechanically ventilated patients with Gram-negative
pneumonia. The enrolment for two pivotal Phase III studies will start in the
fourth quarter of 2008.
About Phase II Studies
High Amikacin Lung Deposition in MVP (2)
In the multi-center, randomized, double-blind, placebo-controlled Phase II
study mechanically ventilated patients (MVP) received 400 mg doses of amikacin
with Amikacin Inhale every 24 hours (n=24) or every 12 hours (n=21) for 7-14
days. Serial serum, tracheal aspirate and urine samples were collected on Day
3. Clinical parameters, such as Clinical Pulmonary Infection Score (CPIS), days
on ventilator and intravenous antibiotic use were monitored. In another study
healthy volunteers (n=14) inhaled a single dose of 400 mg of amikacin via the
proprietary delivery system using the hand held adaptor. This was done to
compare the lung doses between on-vent and hand-held adaptors using the same
proprietary nebulizer.
Mean peak tracheal aspirate of amikacin after Amikacin Inhale use every 12
hours was 16,212±3,675 ?g/mL as compared to 14±4.2 ?g/mL after intravenous
administration (15mg/kg per day)(3). After Amikacin Inhale use, peak serum
levels of amikacin were 3.2±0.5 ?g/mL versus 47±4.2 ?g/mL after intravenous
administration. On average, 43 percent of the dose was delivered to the lungs
using the hand-held system with a comparable low systemic exposure. The dose
delivered to the lungs with the proprietary nebulizer is comparable between the
on-vent and hand-held adaptors.
Penetration of Amikacin Inhale in Lower Respiratory Tract (4)
This study evaluated Amikacin Inhale penetration into the fluid lining of the
epithelial surface (ELF) of the lower respiratory tract of the
pneumonia-infected lung. Treatment was adjunctive to IV treatment. Mechanically
ventilated patients (n=28) with Gram-negative pneumonia received 400 mg doses
of aerosolized amikacin every 12 hours for 7-14 days. The delivery of
aerosolized Amikacin Inhale achieved high aminoglycoside amikacin
concentrations in the ELF of the lower respiratory tract, including in the
pneumonic area of the lung while maintaining safe serum concentrations. Median
ELF levels were 976.1 ?g/mL [135.7-16,127.6], always exceeding the amikacin MIC
(minimum inhibitory concentration) for microorganisms usually responsible for
Gram-negative pneumonia.
High in vivo Amikacin Lung Deposition Correlates with in vitro Findings (5)
This study describes the in-vitro and in-vivo characterization of a hand held
version of Amikacin Inhale, intended for use in extubated patients. In-vitro,
amikacin 400 mg was aerosolized continuously, and emitted mass captured on
absolute filters distal to the mouthpiece during simulated adult tidal
breathing. Emitted mass was 87 percent of the 400 mg amikacin nominal dose,
with a predicted lung dose of 45-50 percent. In-vivo, Amikacin Inhale (400 mg
amikacin) labeled with 99mTc was administered to healthy subjects using the
hand-held version. In these, mean amikacin lung dose determined via
scintigraphy was 172.2 mg, 43 percent of the nominal dose. These results show
that the hand-held drug-device combination delivered a large fraction of the
starting dose, confirming the high delivery efficiency predicted by in vitro
aerosol characterization. The study also confirmed that the in vitro model is
predictive of the in-vivo experience. Lung doses in the range of those observed
are expected to achieve bacteriological eradiation.
Copies of abstracts are available and can be viewed online at the ATS website:
www.abstracts2view.com/ats08/
About Bayer
The Bayer Group is a global enterprise with core competencies in the fields of
health care, nutrition and high-tech materials. Bayer HealthCare, a subsidiary
of Bayer AG, is one of the world's leading, innovative companies in the
healthcare and medical products industry and is based in Leverkusen, Germany.
The company combines the global activities of the Animal Health, Consumer Care,
Diabetes Care and Pharmaceuticals divisions. The pharmaceuticals business
operates under the name Bayer Schering Pharma AG. Bayer HealthCare's aim is to
discover and manufacture products that will improve human and animal health
worldwide. Find more information at www.bayerhealthcare.com.
About Bayer Schering Pharma
Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company.
Its research and business activities are focused on the following areas:
Diagnostic Imaging, General Medicine, Specialty Medicine and Women's
Healthcare. With innovative products, Bayer Schering Pharma aims for leading
positions in specialized markets worldwide. Using new ideas, Bayer Schering
Pharma aims to make a contribution to medical progress and strives to improve
the quality of life. Find more information at www.bayerscheringpharma.de.
About Nektar Therapeutics
Nektar Therapeutics is a biopharmaceutical company that develops and enables
differentiated therapeutics with its industry-leading PEGylation and pulmonary
drug development platforms. Nektar PEGylation and pulmonary technology,
expertise, manufacturing capabilities have enabled nine approved products for
partners, which include the world's leading pharmaceutical and biotechnology
companies. Nektar also develops its own products by applying its pulmonary and
PEGylation technology platforms to existing medicines with the objective to
enhance performance, such as improving efficacy, safety and compliance. Find
more information at www.nektar.com.
