Healthy Skepticism Library item: 13136

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Publication type: news

Damouni S, Czobor K.
Merck’s Gardasil vaccine encounters skepticism from some physicians regarding
Financial Times 2008 Feb 22
http://www.ft.com/cms/s/2/728046c4-e15b-11dc-a302-0000779fd2ac,dwp_uuid=e8477cc4-c820-11db-b0dc-000b5df10621.html

Full text:

Merck’s human papillomavirus (HPV) vaccine Gardasil is seeing physician
skepticism regarding its wide-scale use, as doubts of long-term safety and
efficacy linger, Pharmawire has found. Recent reports have linked deaths and
rare serious adverse events to the vaccine, doctors said.

Since Gardasil’s approval last year, there have been reports which have cited 11
deaths and adverse events which range from Guillan-Barre syndrome, Bells Palsy,
seizures and fainting. The vaccine has also been linked to blood clotting and
heart problems.

Also, out of 42 pregnant women who received the vaccine, 18 had complications
that ranged from fetal abnormalities to miscarriages.

However, Dr Rick Haupt, head of biological clinical research and head of the HPV
Vaccine program at Merck, explained that despite recent news on adverse events,
there is the chance for discrepancies in the reporting of these events.

”Anyone that has adverse events or outcome after vaccination can report it to
different databases that collect safety reports after vaccination,” said Haupt.
“These are reports that are usually temporally related to the vaccine and there
is no adjudication for casualty.”

Haupt also pointed out that deaths reported after vaccination have been based on
hearsay.

”Many of the deaths reported in our database, are associated with known causes
of deaths in this age group,” he said. “Things like there was a report of a
woman who had acute influenza, for example, who died of influenza, and happened
to have had the vaccine”.

Still, a pharmaceutical industry investor noted two recent deaths in Europe
linked to Gardasil appear to have been dismissed. He added that considering an
estimated 10 – 12 million girls and young women are being vaccinated for an
illness that is not considered an epidemic is a dangerous premise. He said there
are approximately 15,000 to 30,000 cases of cervical cancer in the US, and if
caught early it’s almost always curable. He asked, ”It’s not a great vaccine and
so all of a sudden you throw deaths in the mix, is the risk reward all that good?”

Haupt begged to differ regarding the term epidemic. ”I think HPV is an
epidemic,” he said. “It is the most common sexually transmitted infection
worldwide.”

The investor noted that Gardasil is Merck’s profit driver and the company is
counting on the franchise for its continued growth. Any setbacks would severely
hurt the company, he added. In 2007, Gardasil’s actual sales were USD 1.481bn,
and its estimated 2013 peak sales are valued at USD 3,451bn.

Dr Abby Lippman, professor of epidemiology at McGill University, noted HPV is
neither an emergency nor a crisis, and as a consequence advises against the
”mass vaccination” situation that has arisen.

She asked, ”Why can’t we take some time to realize its benefits and harms before
we immunize school girls? Before we have a public health crisis, policies should
be decided on harder data when we don’t have a crisis to deal with.”

An industry investment banker noted that there could be the possibility that
young girls and women could be screened more diligently for Gardasil. Yet, none
of the doctors had any specific comments towards screening or labeling changes
prior to vaccination.

Considering Gardasil only prevents four types of HPV (Types 6, 11, 16, 18), and
that trials were not lengthy, ”as far as risk benefit, you never know the long
term safety concerns are going to be especially if you think about dosing young
girls,” the investor said. Cervical cancer is a very curable cancer, he added.

Still, Kevin Ault, associate professor, department of gynecology and obstetrics
at Emory University School of Medicine, defended Gardasil in relation to its
side effects. There are two well documented cases of Guillain-Barre syndrome – a
neurological disease characterized by reversible paralysis – which in relation
to the size of the population that has been dosed has amounted to a ”rare event
in a huge population.”

He added that blood clots have drawn attention, but that the rate of blood clots
are the same as the rate of blood clots in birth control pills. ”It does not
appear to be causally related to the vaccine,” he said.

Still, physicians are cautious about the effectiveness of Gardasil.

Dr William Bonnez, associate professor of medicine at the infectious diseases
unit, University of Rochester Medical Center, said it is particularly important
for Merck to find out if the rate of cervical cancer decreases after the
administration of the vaccine. ”This is the final proof that is needed to affirm
that the vaccine is effective,” said Bonnez, who also holds intellectual
property rights on the HPV vaccine, and derives royalties from Gardasil, as well
as GlaxoSmithKline’s Cervarix. ”The vaccine protects against the precursor
lesions, we don’t have proof that it prevents the cancer from developing.”

Dr Abby Lippman added that there has been a huge amount of marketing, and that
Gardasil is not a vaccine against cancer, as it only targets the prevention of
HPV. ”We won’t know for 30 years if it makes a difference against cervical
cancer,” she said.

Still, Merck’s Haupt said that the company’s clinical trials were specifically
designed to demonstrate that Gardasil could prevent the highest grade precancers
before the development of cervical cancer, and has therefore demonstrated that
Gardasil prevented 99% of CIN (cervical intraepithelial neoplasia) grades
II/III. These are the highest grade precancers and go on to develop cancer, he
added.

Dr James Colgrove, assistant professor with the center for the history and
ethics of public health at Columbia University’s Mailman School of Public
Health, argued that there are still too many unanswered questions about safety
and efficacy. Colgrove said he considers the Phase III trial that Merck sought
for Gardasil’s approval, as ”a decent sized study,” but said that even with the
largest trials, it is necessary to get post-market information.

Haupt noted that Merck is conducting a long-term study in the Scandinavian
region with a group of women that the company has vaccinated in one of its
largest Phase III trials. Merck is also enrolling in a long-term follow-up study
that will assess the effectiveness of the vaccine over time and the safety of
that population. The company is also seeking new medical conditions, such as
pregnancies that occur in those women over a period of time.