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GSK gearing up to file pandemic flu vaccine
 
 
  www.pharmatimes.com
26/07/2006
 
GlaxoSmithKline says it is only months away from filing for approval of a vaccine against the H5N1 strain of avian influenza, currently thought to be the most likely to cause a flu pandemic in humans, after promising results in clinical trials.
 
An interim analysis of a 400-patient trial conducted in Belgium suggests that GSK's formulation - which includes just 3.8mcg of H5N1 antigen and includes a novel, proprietary adjuvant to boost its activity - stimulated a protective immune response in over 80% of subjects.
 
Trial participants were vaccinated twice during the course of the trial and four different levels of antigen dose were tested, with 3.8mcg being the lowest dose assessed.
 
The use of the adjuvant means that scarce supplies of the H5N1 antigen can be stretched further, and GSK's chief executive Jean-Pierre Garnier told the Today programme on the BBC's Radio 4 this morning that it could be in a position to produce 'hundreds of millions' of doses by the end of the year, and could also cost as little as 4 a dose, roughly equivalent to the price of seasonal flu vaccines.
 
'Home-grown' H5N1 vaccine nears trials in UK
 
11/07/2006
 
UK biotechnology company PowderMed has asked for approval to start clinical trials of a 'rapid response' vaccine for the H5N1 strain of avian influenza.
 
Although other vaccines against H5N1 are further forward in development, PowderMed believes that its candidate, which is based on viral DNA, could have an advantage in terms of speed of production over vaccines made in either eggs or cell culture-based systems.
 
The plasmid DNA for PowderMed's vaccine is produced using a bacterial fermentation process that could carve the production time down from nine months with egg-based systems to a matter of weeks, which could make for rapid production of vaccine in response to a rapidly-emerging pandemic strain.
 
If the strain of virus causing an influenza pandemic mutated, it would be relatively simple to isolate the new strain, get hold of its key DNA sequences and produce new vaccine. Moreover, the use of DNA means that limited supplies of vaccine antigen can be stretched further: PowderMed estimates that 1 kg of H5N1 DNA could be manufactured in just three months and provide enough antigen to vaccinate the UK population of 60 million people twice over.
 
PowderMed aims to carry out the trial at a clinical research centre in London, which is already involved in recruiting patients for flu vaccine trials. It hopes the findings will back up results from a US study of a seasonal flu vaccine, reported in the journal Vaccine, which showed that the vaccine achieved 100% efficacy in stimulating antibodies against the virus.
 
Information on the trial published on the www.clinicaltrials.gov website indicates that it will enroll a target group of 75 adult volunteers and is scheduled to get underway this month, with completion in May 2007. It will look at four different doses of the vaccine, given as a prime-boost regimen on days 0 and 28.
 
The vaccine takes the form of microscopic gold particles, coated with DNA, that are shot through the skin and penetrate local immune cells in order to stimulate a response.
 
Crucell starts trial of bird flu vaccine
 
- 31/05/2006
 
Dutch biotechnology company Crucell has joined the ranks of companies seeking to develop vaccines against avian influenza, starting a trial of three versions of a candidate targetted against the H9N2 strain of bird flu.
 
While most of its larger vaccine rivals - including Sanofi-Aventis, GlaxoSmithKline and Novartis (via Chiron) - are concentrating on the H5N1 strain of bird flu as the most likely to cause a pandemic in humans, other strains, including H9 and H7 have also caused lethal outbreaks among birds in the past.
 
Crucell also intends to develop vaccine candidates against the H5N1 strain, and said this preliminary testing on H9N2 would help plan that programme.
 
The trial will be performed in collaboration with a team based in Leicester, UK, and will involve 560 healthy adults who will receive either a non-adjuvanted whole virion vaccine, an alum-adjuvanted whole virion vaccine and a virosomal subunit vaccine, all based on the H9N2 virus. The whole virion vaccine will be administered by both intramuscular and intradermal routes, with the latter of particular interest as it may allow a lower dose of antigen to be used, and so allow supplies to stretch farther in the event of a pandemic.
 
Crucell said it expects to have the results of its testing by the end of the year, noting that trials of this type can be used in support of a "pandemic core dossier", which forms the basis for rapid approval by the regulatory authority of a vaccine against an actual pandemic threat once it emerges.
 
Two cheers for bird flu vaccine
 
- 30/03/2006
 
A vaccine against the H5N1 strain of bird flu, developed by Sanofi Pasteur, was effective in a clinical trial but only at the highest dose tested, sharply reducing the number of people who could be protected using existing stockpiles.
 
The 451-patient study included a range of doses of the vaccine candidate - from 7.5mcg to 90mcg - but only the highest dose were antibodies produced in quantities sufficient to protect against bird flu.
 
"The need for a vaccine with a total dose of 180mcg would pose a considerable barrier to rapid production of a supply that would be adequate to meet the world's requirements should a pandemic occur," they said. One solution could be to include the use of an immune response-boosting adjuvant such as alum in the vaccine formulation.
 
In December, Sanofi Pasteur said another trial suggested two 30mcg doses of the vaccine given with an alum was able to produce an immune response comparable to that achieved with current vaccines used to protect against seasonal flu.
 
The researchers also noted they had set the threshold for an effective immune response quite high in the current study, and it was possible a lower antibody response could still be effective.
 
The USA has spent more than $150 million laying down supplies of the bulk antigen used in Sanofi Pasteur's H5N1 vaccine, and has set itself a target of having enough to vaccinate 20 million people. But the current data suggest stocks will only be enough to dose 4 million people, according to Anthony Fauci, the director of the US National Institute of Allergy and Infectious Diseases.
 
Avian flu has infected 186 people in eight countries and killed 105, according to the latest World Health Organisation figures.
 
A number of other companies are working on the development of pandemic flu vaccines, in most cases based on the H5N1 strain, including GlaxoSmithKline, Chiron, Akzo Nobel, MedImmune and Baxter International.
 
GSK vaccine starts trials
 
GSK said today it had started clinical trials of two H5N1 vaccines in humans and was on track to have a candidate in production by the end of the year.
 
A German trial is testing a vaccine that includes alum, while a second study in Belgium is looking at a vaccines incorporating a novel adjuvant. Preliminary results from the trials are expected in the third quarter.
 
Meanwhile, GSK reported that its inhaleable flu drug Relenza (zanamivir) has been approved in the USA for the prevention of influenza in adults and children aged five years and older. The drug was already registered for treating flu, and the approval puts it on level terms with Roche's oral flu drug Tamiflu (oseltamivir). Fears of a pandemic drove sales of Tamiflu to 1.6 billion Swiss francs ($1.2bn) last year, around half of which came from government orders.
 
Encouraging data with Sanofi's H5N1 vaccine
 
- 12/05/2006
 
A candidate vaccine against the H5N1 strain of avian influenza, developed by French drugmaker Sanofi-Aventis, has been found to be safe and effective in a Phase I trial published yesterday in The Lancet.
 
The vaccine, developed by Sanofi Pasteur, is based on a modified strain of the virus. Two doses of the candidate produced protective antibodies in the trial, which involved 300 healthy volunteers.
 
The authors of the study said the regimen of two 30mcg doses was safe - with only a few cases of adverse reactions - and achieved an antibody response "consistent with European regulatory requirements for licensure of seasonal influenza vaccine."
 
However, they cautioned that the actual level of antibodies that would provide protection against H5N1 is currently unknown.
 
The study involved several formulations of the vaccine, half of which were adjuvanted with alum, with the 30mcg version using an adjuvant performing the best with a 67% seroconversion rate. But there were encouraging responses with lower doses of the vaccine, which could mean that currently limited stocks of the antigen could be stretched further in the event of an H5N1 flu pandemic.
 
A study of a similar, unadjuvanted candidate H5N1 vaccine produced by Sanofi Pasteur in the USA that was published in the New England Journal of Medicine in March required two 90mcg doses to generate a significant immune response in about 50% of trial participants, leading to fears that antigen stocks laid in by the US government would only provide a quarter of the number of doses initially envisaged.
 
Lancet editor Richard Horton said the results were particularly encouraging and mean that it should be possible of developing an effective vaccine over the next 12 to 18 months.
 
A number of other companies are working on the development of pandemic flu vaccines, in most cases based on the H5N1 strain, including GlaxoSmithKline, Chiron, Akzo Nobel, MedImmune and Baxter International.
 
All told, 31 vaccines against bird flu are currently being tested in clinical trials, with 22 targetting the H5N1 strain which has infected 186 people in eight countries and killed 105, according to the latest World Health Organisation figures. Eight vaccines will have undergone Phase II trials by the end of 2006
 
 
 
 
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