Bayer Schering Pharma Collaborates With AC Immune in The Field of Alzheimer´s Disease

Florbetaben will be used for the very first time in Alzheimer´s patients being treated with a vaccination therapy.

Bayer Schering Pharma AG, Germany, will provide its development candidate florbetaben, a so called PET (positron emission tomography) tracer, to the Swiss-based biopharmaceutical company AC Immune SA, to support a clinical trial in the field of Alzheimer´s disease (AD). This study is conducted to develop a therapy option for the treatment of AD. Bayer´s novel PET tracer florbetaben will be applied for imaging of beta-Amyloid deposition in the brain of patients undergoing the phase I clinical testing of AC Immune´s Alzheimer´s vaccine ACI-24. In this collaboration, florbetaben will be tested for the very first time in the development of a potential therapeutic for Alzheimer’s patients.

“Bayer Schering Pharma has already demonstrated the potential of florbetaben to image beta-Amyloid deposition in the brain in its own phase II study,” said Dr. Thomas Balzer, Head of Global Clinical Development Therapeutic Area Diagnostic Imaging at Bayer Schering Pharma. “The cooperation with AC Immune enables the collection of valuable clinical data for florbetaben in patients treated with AC Immune’s novel therapeutic vaccine.”

”This collaboration with Bayer Schering Pharma adds further value to our Alzheimer´s vaccine ACI-24,” said Prof. Andrea Pfeifer, CEO of AC Immune. “The adoption of a diagnostic imaging substance visualizing the deposition of beta-Amyloid that is targeted by our vaccine can be an important parameter for dose selection, and will provide useful complementary data. There is a key trend in the industry to co-develop therapy guiding diagnostics alongside drugs for patients. We look forward to working with Bayer´s experts in this ground-breaking collaboration.”

Currently, there is no diagnostic test on the market that can detect beta-Amyloid deposition in the brain – a pathological hallmark of Alzheimer´s disease – in patient´s lifetime. Today, the clinical diagnosis of AD is based on cognitive tests, Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT) scans to exclude other dementia diseases. Unfortunately, clinical diagnosis is often made too late and does not always correlate with post-mortem diagnosis. A good diagnostic assay should also help to better evaluate the effect of new treatments in clinical trials as well as correlate better with existing pathological and memory markers. A new diagnostic tool to detect beta-Amyloid in the brain in vivo might also be beneficial in detecting the disease earlier, before the symptoms are too advanced so treatment could be started earlier.

About Florbetaben (18 F)
Florbetaben is an inlicensed 18F-labeled PET tracer that specifically binds to deposition of beta-Amyloid. These depositions (plaques) consist of proteins that accumulate in the brain and are a pathological hallmark of Alzheimer’s disease. As the aggregation of the beta-Amyloid protein in the brain is also a key target for new therapeutic treatments under development, florbetaben might also be able to support the development of these new treatment approaches. A phase II study showed that patients with clinical diagnosis of Alzheimer´s disease could be differentiated from age-matched healthy volunteers on the basis of florbetaben uptake pattern in the brain. The results of this study were presented at the International Conference on Alzheimer’s diseases (ICAD) in Vienna, Austria in July 2009.
Find more information at www.viva.vita.bayerhealthcare.com

About ACI-24
ACI-24 is an active vaccine stimulating the patient's immune system to produce beta-sheet conformation-specific antibodies that prevent plaque deposition or enhance its clearance. During preclinical development, the ACI-24 has shown high efficacy in vivo by memory restoration and plaque reduction. The vaccine is also characterized by a very high specificity due to generating a conformation-specific antibody response. The favourable safety profile of ACI-24 is underlined through the absence of local inflammation in relevant models as well as its T-cell independent mechanism shown in preclinical development.

About the ACI-24 clinical trial
It is a phase I, randomized, double blind, placebo controlled clinical study with the primary objective of evaluating the safety and tolerability of ACI-24 and a secondary objective of evaluating efficacy (immune response and clinical assessment) in mild to moderate AD patients. Phase I is designed to allow for the identification of the best dose of vaccine to be used further in phase II. Three groups of patients, each receiving a different dose of ACI-24, will be observed.

About Alzheimer’s Disease
Alzheimer’s disease is a devastating neuro-degenerative disease and the most common cause of dementia. Most cases of Alzheimer’s disease affect people over the age of 60. It is a progressive disease that can lead to premature death. In 2006, estimates suggested that more than 26 million people worldwide were suffering from Alzheimer’s disease. By 2050, this number could reach more than 100 million. At present there is no cure for Alzheimer’s disease, but treatments for symptoms, combined with the right services and support, can make life better for the millions of people living with Alzheimer’s.

Immunization prevents 2.5 million child deaths every year

Vaccination against vaccine-preventable diseases is essential to reaching the Millennium Development Goal 4 on reducing under-five mortality by two thirds by 2015, according to World Health Organisation. Immunization is also a key strategy to ensure global health security and for responding to the threat of emerging infections such as pandemic influenza.

For the first time in documented history, the number of children dying every year has fallen below ten million — partly the result of improved access to immunization, integrated delivery of essential health interventions, as well as clean water and sanitation.

Immunization prevents an estimated 2.5 million child deaths every year in all age groups from diphtheria, tetanus, pertussis (whooping cough), and measles. It is one of the most successful and cost-effective public health interventions.

More children than ever are being reached with immunization. In 2008, an estimated 106 million children under the age of one were vaccinated with three doses of diphtheria―tetanus―pertussis (DTP3) vaccine. These children are protected against infectious diseases that can have serious consequences like illness, disability or death.

Despite the progress, an estimated 24 million children under the age of one did not receive the DTP3 vaccine doses in 2008. About three quarters of these children live in ten countries: Chad, China, Democratic Republic of the Congo, Ethiopia, India, Indonesia, Iraq, Nigeria, Pakistan and Uganda.

An estimated 1.3 million infants and young children die every year from pneumococcal disease and rotavirus diarrhoea. A large number of these deaths can be prevented through vaccination.

A large number of vaccine products are currently in the pipeline and are expected to become available by 2012. More than 80 candidate vaccines are in the late stages of clinical testing. About 30 of these candidate vaccines aim to protect against major diseases for which no licensed vaccines exist, such as dengue and malaria.

The Meningitis Vaccine Project is working on a new meningococcal vaccine. Meningitis A epidemics severely affect certain sub―Saharan countries. A first―generation malaria vaccine has also demonstrated some level of efficacy in young children and may be available by 2015.

Vaccination has led to the elimination of measles in the WHO Region of the Americas. Global measles mortality has decreased by 74% from 750 000 deaths in 2000 to 197 000 deaths in 2007, thanks to intensified vaccination campaigns.

Polio has been eradicated in three of WHO’s six regions and is today endemic in only four countries ― Afghanistan, India, Nigeria and Pakistan ― down from 125 countries in 1988. Annual deaths from neonatal tetanus have fallen to an estimated 128 000, down from 790 000 deaths in 1988.

Immunization not only protects children from vaccine―preventable diseases. It also serves as a means to deliver other life―saving measures, such as vitamin A supplements to prevent malnutrition, insecticide―treated nets for protection against malaria and deworming medicine for intestinal worms.

How Should Influenza in Patients With Asthma Be Treated

Patients with asthma who have suspected or confirmed influenza should be strongly considered for antiviral medications because of their increased risk of developing a complication of influenza, said researchers from American Academy of Allergy Asthma&Immunology. Data from randomized controlled trials for antiviral medications for patients with asthma are limited; 1 trial demonstrated a decreased risk of asthma exacerbation (defined by changes in peak flow) in the oseltamivir group compared with placebo but did not meet its primary endpoint of demonstrating a difference in time to freedom from illness. Patients with asthma who present with concerning signs and symptoms of lower respiratory tract infection and suspected influenza should be treated with antiviral medication even if more than 48 hours have elapsed since symptoms started. In addition, patients with asthma should be treated for asthma exacerbation per their personalized written asthma action plan. Complications of influenza infection such as bacterial pneumonia should be considered. Evaluation of fatal pediatric 2009 H1N1 influenza cases found Staphylococcus aureus to be the most common bacteria isolated (including some cases of methicillin-resistant S aureus).

Antiviral medication choice depends on the influenza strain type and resistance patterns. Strain type can be obtained directly from test results (if the RT-PCR technique is used) or can be estimated by community surveillance reports. Seasonal influenza A H1N1-type (not 2009 H1N1) is resistant to oseltamivir, whereas type A H3N2-type is not. The influenza type B strain that circulated in the 2008 to 2009 season was susceptible to oseltamivir. Two of the type A strains that circulated most in the 2008 to 2009 season are expected to circulate in the 2009 to 2010 season and are included in the 2009 to 2010 seasonal influenza vaccine. Current recommendations are based on 2008 to 2009 season circulation and resistance data and will be updated when additional data become available. Oseltamivir is recommended for influenza B, influenza A H3N2-like, and 2009 H1N1. Zanamivir or a combination of rimantadine and oseltamivir is recommended for influenza A seasonal H1N1-like because of oseltamivir resistance. If the chosen testing method does not distinguish between influenza A strains, a
combination of oseltamivir and rimantadine is recommended for patients with asthma. If novel H1N1 influenza is the dominant circulating strain and antiviral resistance does not emerge, oseltami- vir may become the recommended antiviral for strains that cannot be confirmed. Zanamivir is active against all currently circulating influenza strains but should be used cautiously in patients with asthma because of case reports of severe bronchospasm.
Oseltamivir is the preferred antiviral medication for pregnant patients and children <7.> Patients with asthma who are not vaccinated against influenza at the time of diagnosis should be offered vaccination with TIV (for seasonal or 2009 H1N1) along with antiviral treatment.
Those with fever should not be vaccinated until the fever resolves.


Conclusions and key points for patients with asthma:

• Vaccinate with seasonal and 2009 H1N1 TIV unless there is a strong contraindication such as current febrile illness or Guillain-Barre´ syndrome within 6 weeks of previous influenza vaccination.
  

• Patients with asthma concerned about influenza vaccine allergy (including a convincing clinical history of egg allergy) should be evaluated by an allergist/immunologist.
  

• Consider whether testing for influenza will change treatment recommendations; when testing, strongly consider the RT-PCR testing method.
  

• Treat asthma patients with antiviral medications based on circulating strains and resistance patterns.