PowderMed Manufactures a Vaccine Against H5N1 (Avian Influenza) for Clinical Development

OXFORD, England--(BUSINESS WIRE)--Aug. 1, 2005--PowderMed, the immunotherapeutics company focused on the development and manufacture of DNA-based vaccines for viral diseases and cancer, has announced that it has progressed its H5N1 Avian Influenza Vaccine programme into the final stages of preclinical development. PowderMed has produced an H5N1 vaccine by cloning the H5 gene from the current circulating avian flu strain ("the gene cassette") into the company's proprietary DNA vaccine backbone and the vaccine is now ready for development. Manufacturing and toxicology studies are now in progress, and it is anticipated that this vaccine will enter clinical trials by the middle of 2006.

 

Commenting on the programme, Dr Clive Dix, CEO of PowderMed said:

"We are very excited by the potential for our flu vaccine technology to address the major healthcare challenge that influenza presents, in particular in the event of an avian flu or other pandemic outbreak. Our technology has significant advantages over current flu vaccine technology particularly in terms of the speed of response in the event of a pandemic. As soon as a new influenza strain becomes known, our "plug and play" system would enable us to rapidly insert the relevant DNA gene cassette into our standard DNA backbone. A PowderMed manufacturing facility will be capable of delivering the vaccine requirements of an entire country within 3 months. This is not possible for other technologies."

Just 1.2kg of vaccine DNA would be sufficient to vaccinate the entire population of the US twice - an initial dose and a booster dose. PowderMed has carried out a detailed feasibility study with contract manufacturing partners, which concludes that it could establish a manufacturing capability with a surge capacity of 150 million influenza vaccine doses in a three-month period. Dr Dix points out that this is critical since, "No other vaccine technology offers this speed of response. In the event of a pandemic, most deaths and illness will occur in the first six months of an outbreak. We believe that our technology offers the best potential to save lives and minimise the economic impact of a flu pandemic."

The Avian flu vaccine uses the same standard DNA vaccine backbone as PowderMed's annual flu vaccine, which has already successfully completed a Phase I clinical trial (www.powdermed.com/media.htm) and will enter Phase IIb trials in 2006.

Today 4:00:00 AM -

... they view as an inevitable influenza pandemic say the world lacks the medical weapons to fight... World Not Set To Deal With Flu Strategy for Pandemic Needed, Experts Say By David Brown Washington... dangerous strain of influenza to appear in decades -- the H5N1 "bird flu" in Asia -- is showing up ...

Public health officials preparing to battle what they view as an inevitable influenza pandemic say the world lacks the medical weapons to fight the disease effectively, and will not have them anytime soon.

Public health specialists and manufacturers are working frantically to develop vaccines, drugs, strategies for quarantining and treating the ill, and plans for international cooperation, but these efforts will take years. Meanwhile, the most dangerous strain of influenza to appear in decades -- the H5N1 "bird flu" in Asia -- is showing up in new populations of birds, and occasionally people, almost by the month, global health officials say.

If the virus were to start spreading in the next year, the world would have only a relative handful of doses of an experimental vaccine to defend against a disease that, history shows, could potentially kill millions. If the vaccine proved effective and every flu vaccine factory in the world started making it, the first doses would not be ready for four months. By then, the pathogen would probably be on every continent.

Theoretically, antiviral drugs could slow an outbreak and buy time. The problem is only one licensed drug, oseltamivir, appears to work against bird flu. At the moment, there is not enough stockpiled for widespread use. Nor is there a plan to deploy the small amount that exists in ways that would have the best chance of slowing the disease.

The public, conditioned to believe in the power of modern medicine, has heard little of how poorly prepared the world is to confront a flu pandemic, which is an epidemic that strikes several continents simultaneously and infects a substantial portion of the population.

Since the current wave of avian flu began sweeping through poultry in Southeast Asia more than 18 months ago, international and U.S. health authorities have been warning of the danger and trying to mobilize. Research on vaccines has accelerated, efforts to build up drug supplies are underway, and discussions take place regularly on developing a coordinated global response.

The U.S. Department of Health and Human Services will spend $419 million in pandemic planning this year. The National Institutes of Health's influenza research budget has quintupled in the past five years.

"The secretary or the chief of staff -- we have a discussion about flu almost every day," said Bruce Gellin, head of HHS's National Vaccine Program Office. This week, a committee is scheduled to deliver to HHS Secretary Mike Leavitt an updated plan for confronting a pandemic.

Despite these efforts, the world's lack of readiness to meet the threat is huge, experts say.

[...]

The most outspoken is Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. In writing and in speeches, Osterholm reminds his audience that after public calamities, the United States usually convenes blue-ribbon commissions to pass judgment. There will be one after a flu pandemic, he believes.

"Right now, the conclusions of that commission would be harsh and sad," he said.

The influenza pandemic of 1918-1919 killed more people than
the Great War, known today as World War I (WWI), at
somewhere between 20 and 40 million people. It has been
cited as the most devastating epidemic in recorded world
history. More people died of influenza in a single year than
in four-years of the Black Death Bubonic Plague from 1347 to
1351. Known as "Spanish Flu" or "La Grippe" the influenza of
1918-1919 was a global disaster.

[...]

The flu was most deadly for people ages 20 to 40. This
pattern of morbidity was unusual for influenza which is
usually a killer of the elderly and young children. It
infected 28% of all Americans (Tice). An estimated 675,000
Americans died of influenza during the pandemic, ten times
as many as in the world war. Of the U.S. soldiers who died
in Europe, half of them fell to the influenza virus and not
to the enemy (Deseret News). An estimated 43,000 servicemen
mobilized for WWI died of influenza (Crosby).

The effect of the influenza epidemic was so severe that the
average life span in the US was depressed by 10 years. The
influenza virus had a profound virulence, with a mortality
rate at 2.5% compared to the previous influenza epidemics,
which were less than 0.1%. The death rate for 15 to
34-year-olds of influenza and pneumonia were 20 times higher
in 1918 than in previous years (Taubenberger). People were
struck with illness on the street and died rapid deaths. One
anectode shared of 1918 was of four women playing bridge
together late into the night. Overnight, three of the women
died from influenza (Hoagg). Others told stories of people
on their way to work suddenly developing the flu and dying
within hours (Henig). One physician writes that patients
with seemingly ordinary influenza would rapidly "develop the
most viscous type of pneumonia that has ever been seen" and
later when cyanosis appeared in the patients, "it is simply
a struggle for air until they suffocate," (Grist, 1979).
Another physician recalls that the influenza patients "died
struggling to clear their airways of a blood-tinged froth
that sometimes gushed from their nose and mouth," (Starr,
1976). The physicians of the time were helpless against this
powerful agent of influenza. In 1918 children would skip
rope to the rhyme (Crawford):

I had a little bird,

Its name was Enza.
I opened the window,
And in-flu-enza.

DAVID BROWN IS
SOUNDING THE BIRD FLU ALARM in the
Washington Post.

Public health officials preparing to battle what they
view as an inevitable influenza pandemic say the world lacks
the medical weapons to fight the disease effectively, and
will not have them anytime soon.

Public health specialists and manufacturers are working
frantically to develop vaccines, drugs, strategies for
quarantining and treating the ill, and plans for
international cooperation, but these efforts will take
years. Meanwhile, the most dangerous strain of influenza to
appear in decades -- the H5N1 "bird flu" in Asia --
is showing up in new populations of birds, and occasionally
people, almost by the month, global health officials say.

If the virus were to start spreading in the next year,
the world would have only a relative handful of doses of an
experimental vaccine to defend against a disease that,
history shows, could potentially kill millions.

Read the whole thing. And then worry a bit.

UPDATE: Reader Jim McMurry emails:

The worries about bird flu are past the realm of "could
be a threat" and have entered the phase of the ticking time
bomb and we cannot see the time marker, nor know when it
will go off in the USA. I am betting on October 2006, but it
could come sooner.

Well, we don't know. A major flu pandemic is pretty much
inevitable sooner or later. On the other hand, many of the
casualties from the 1918 flu were people who were weakened by
TB, meaning that perhaps lethality won't be as bad this time.
But I certainly think that we need to be working hard on
antiviral drugs, and protocols for the rapid production of new
vaccines, not only to be ready for bird flu but to be ready for
all kinds of potential natural and unnatural outbreaks.

Yesterday 3:03:41 PM -

Public health officials preparing to battle what they view
as an inevitable influenza pandemic say the world lacks the
medical weapons to fight the disease effectively, and will
not have them anytime soon.

Public health specialists and manufacturers are working
frantically to develop vaccines, drugs, strategies for
quarantining and treating the ill, and plans for
international cooperation, but these efforts will take
years. Meanwhile, the most dangerous strain of influenza to
appear in decades—the H5N1 “bird
flu” in Asia—is showing up in new populations of birds, and
occasionally people, almost by the month, global health
officials say.

If the virus were to start spreading in the next year,
the world would have only a relative handful of doses of an
experimental vaccine to defend against a disease that,
history shows, could potentially kill millions. If the
vaccine proved effective and every flu vaccine factory in
the world started making it, the first doses would not be
ready for four months. By then, the pathogen would probably
be on every continent.

Theoretically, antiviral drugs could slow an outbreak and
buy time. The problem is only one licensed drug,
oseltamivir, appears to work against bird flu. At the
moment, there is not enough stockpiled for widespread use.
Nor is there a plan to deploy the small amount that exists
in ways that would have the best chance of slowing the
disease.

This isn’t going away, it can’t be negotiated, so we better
start preparing. Just as a curious side note, the the late night
crazies at Art Bell’s
Coast to Coast have been
fretting about
this for years.

There is an ember of hope that avian flu might be stopped
soon, while it remains only a spark and not a raging
conflagration.

Will the nations with the most to lose economically gamble on
the altruistic (read: economic self-preservation) move to put
out the small fires in Indonesia, Viet Nam and Thailand by
sending their supplies of antivirals and vaccines there to
possibly contain the spread? A recent
Washington Post article points out that...

"... unless antiviral drugs squelch a pandemic at the
outset, their ultimate usefulness will be small. ... In
theory, even a modest amount of vaccine might be useful.
Fighting disease outbreaks is like fighting fires. You do
not have to hose down the whole world to put the fire out,
but you do have to hose down the perimeter to keep it from
spreading. It might be possible to contain an H5N1
outbreak at its source if the surrounding population were
immediately vaccinated.

Would the United States, Europe and Japan be willing to
donate their precious vaccine supply to mount this long-shot
defense? This is perhaps the biggest unanswered question in
pandemic flu planning -- and one likely to be answered only
at the moment of truth.

Officially, it is a possibility.

If it was done in consultation with the World Health
Organization -- and with other governments that would make
contributions, as well -- we would be more likely to
consider it," said Gellin at HHS. But observers both in and
out of the government said, not for quotation, that they
doubt the U.S. government would ever send a significant
amount of its vaccine stockpile overseas.
 

Even if this scenario played out and we gave up our
stockpiles to put out small fires overseas, there remains the
wildcard of spread over vast distance by bird migration (or
infected airline passengers) starting too many small fires to
handle; and the barrier of secrecy and disinformation across the
vast Chinese borders where a significant brush fire may already
be spreading.

We (global mankind, science and public health) have not
adequately anticipated and prepared for such a scenario, even
though
we could have seen it coming for a decade or more. If we
could turn back time 15 years and know with certainty the
pathogens we would face in the future, would there have been any
better cooperation between continents? Would we have wasted so
much talent, wealth and technology (ostensibly) to protect our
people and way of life from acts of terrorism if we'd accepted
that it was emerging infectious disease that posed by far the
greater threat to our economy and to our very survival?

It seems we may be very near the moment of truth. Is it too
late to turn our swords into vaccines?

World Not Set To Deal With Flu
Strategy for Pandemic Needed, Experts Say

By David Brown
Washington Post Staff Writer
Sunday, July 31, 2005; A01

Public health officials preparing to battle what they
view as an inevitable influenza pandemic say the world lacks
the medical weapons to fight the disease effectively, and
will not have them anytime soon.

Public health specialists and manufacturers are working
frantically to develop vaccines, drugs, strategies for
quarantining and treating the ill, and plans for
international cooperation, but these efforts will take
years. Meanwhile, the most dangerous strain of influenza to
appear in decades — the H5N1 “bird flu” in Asia — is
showing up in new populations of birds, and occasionally
people, almost by the month, global health officials say.

If the virus were to start spreading in the next year,
the world would have only a relative handful of doses of an
experimental vaccine to defend against a disease that,
history shows, could potentially kill millions. If the
vaccine proved effective and every flu vaccine factory in
the world started making it, the first doses would not be
ready for four months. By then, the pathogen would probably
be on every continent.

Theoretically, antiviral drugs could slow an outbreak and
buy time. The problem is only one licensed drug,
oseltamivir, appears to work against bird flu. At the
moment, there is not enough stockpiled for widespread use.
Nor is there a plan to deploy the small amount that exists
in ways that would have the best chance of slowing the
disease.

The public, conditioned to believe in the power of modern
medicine, has heard little of how poorly prepared the world
is to confront a flu pandemic, which is an epidemic that
strikes several continents simultaneously and infects a
substantial portion of the population.

Since the current wave of avian flu began sweeping
through poultry in Southeast Asia more than 18 months ago,
international and U.S. health authorities have been warning
of the danger and trying to mobilize. Research on vaccines
has accelerated, efforts to build up drug supplies are
underway, and discussions take place regularly on developing
a coordinated global response.

The U.S. Department of Health and Human Services will
spend $419 million in pandemic planning this year. The
National Institutes of Health’s influenza research budget
has quintupled in the past five years.

“The secretary or the chief of staff — we have a
discussion about flu almost every day,” said Bruce Gellin,
head of HHS’s National Vaccine Program Office. This week, a
committee is scheduled to deliver to HHS Secretary Mike
Leavitt an updated plan for confronting a pandemic.

Despite these efforts, the world’s lack of readiness to
meet the threat is huge, experts say.

“The only reason nobody’s concerned the emperor has no
clothes is that he hasn’t shown up yet,” Harvey V. Fineberg,
president of the National Academy of Sciences’ Institute of
Medicine, said recently of the world’s efforts to prepare
for pandemic flu. “When he appears, people will see he’s
naked.”

Other scientists are sounding the alarm as well.

The most outspoken is Michael T. Osterholm, director of
the Center for Infectious Disease Research and Policy at the
University of Minnesota. In writing and in speeches,
Osterholm reminds his audience that after public calamities,
the United States usually convenes blue-ribbon commissions
to pass judgment. There will be one after a flu pandemic, he
believes.

“Right now, the conclusions of that commission would be
harsh and sad,” he said.

In hopes of slowing a pandemic’s spread, public health
specialists have been debating proposals for unprecedented
countermeasures. These could include vaccinating only
children, who are statistically most likely to spread the
contagion; mandatory closing of schools or office buildings;
and imposing “snow day” quarantines on infected families —
prohibiting them from leaving their homes.

Other measures would go well beyond the conventional
boundaries of public health: restricting international
travel, shutting down transit systems or nationalizing
supplies of critical medical equipment, such as surgical
masks.

But Osterholm argues that such measures would fall far
short. He predicts that a pandemic would cause widespread
shutdowns of factories, transportation and other essential
industries. To prepare, he says, authorities should identify
and stockpile a list of perhaps 100 crucial products and
resources that are essential to keep society functioning
until the pandemic recedes and the survivors go back to
work.

At last, front page Sunday treatment of this story. Of
course, if you’ve been reading Just a Bump in the Beltway for a while this is not news to
you.

Charles Roten put up a list of resources
if you
want further information back in June. And, of course, there
is The Flu Wiki, which has
now become the gathering place in English for all things flu. If
you read nothing else, study
CanadaSue’s imagined scenario for her hometown, Kingston,
Ontario.

The Post article, while lengthy, doesn’t spend any time on 1.
why this is important; 2. the potential sequalae of such a
pandemic; 3. the miserable failure of the government to do any
planning. Mike Osterholm is hardly the only scientist who has
been screaming bloody murder about H5N1 for some time.
That said, I heard NIAID’s Tony Fauci on
Diane
Rehm’s NPR show last week, and half of what he said was
talking out of his ass (or covering it.) If I know that, and I’m
no scientist, what else are we missing? It will show up on The
Flu Wiki, for sure.

Saturday, July 30, 2005 12:49:21 AM -