[Ip-health] Hopeless in herpes: Novartis suppress the data

[James Love]

Interesting story from Pharmawatch about the suppression of data from
clinical trials regarding two drugs for the treatment of herpes --
famciclovir and valaciclovir.

*  the pharmaceutical companies are loathe to actually conduct
anything that resembles a real-world head-to-head clinical trial with
their "franchise" unless they are sure of the likely result beforehand.

* But there has been a head to head trial. In 1997. That=92s nearly a
decade ago. So why hasn=92t it been published?

* That ten year old trial data, just published in the journal
Sexually Transmitted Diseases (Vol 33, page 529) showed that
famciclovir was inferior to valaciclovir in suppressing the herpes
virus and preventing viral shedding (and thus preventing
transmission). The researchers said these differences might not have
much clinical significance, but they not unreasonably concluded that
given a choice, and all other things being equal, it would make sense
to use valaciclovir. Not the kind of message Novartis would like to
hear. Especially for a billion dollar blockbuster. And that,
presumably, is why they have sat on this data for the last six years
(The Famvir patent runs out in a couple of years).

* More incredibly, even after all this time the researchers did not
actually get access to the original data. They were given cherry-
picked figures from a Novartis "in house review". They weren't
allowed to see the raw data that would allow them to make a more
meaningful comparison of the two drugs:

* So to sum up. We have data showing that a billion dollar drug is
inferior compared to another drug. This data doesn't get to see the
light of day for almost a decade, and even then, the researchers
aren't allowed to see the true figures. If that's not a scandal I
don't know what it.

http://pharmawatch.blogspot.com/2006_08_01_pharmawatch_archive.html

Tuesday, August 29, 2006
Hopeless in herpes: Novartis suppress the data

Famciclovir and valaciclovir are the two most popular antiviral drugs
for treating herpes. They are big money-spinning blockbusters =96
valaciclovir makes $1.5 billion a year in the US alone. Not much to
choose between them really, if you look at the clinical trial data.
Well, actually there isn=92t any data. As per usual, the pharmaceutical
companies are loathe to actually conduct anything that resembles a
real-world head-to-head clinical trial with their =93franchise=94 unless
they are sure of the likely result beforehand. Believe it or not
there have never been any studies published directly comparing the
two drugs in the treatment of genital herpes. That=92s right. All the
studies have compared them with creaky old acyclovir

But there has been a head to head trial. In 1997. That=92s nearly a
decade ago. So why hasn=92t it been published?

Well here is where it gets murky. Back in the last century,
valaciclovir was marketed by Glaxo (as Valtrex). Famciclovir was
marketed by Smithkline Beecham (as Famvir). When the two companies
merged in 2000, regulators insisted that the new GSK would have to
divest itself of one of the antivirals to avoid a herpes treatment
monopoly situation. So they offloaded Famvir to Novartis, along with
all the clinical trial data. And that=92s where the data has remained
until this month.

That ten year old trial data, just published in the journal Sexually
Transmitted Diseases (Vol 33, page 529) showed that famciclovir was
inferior to valaciclovir in suppressing the herpes virus and
preventing viral shedding (and thus preventing transmission). The
researchers said these differences might not have much clinical
significance, but they not unreasonably concluded that given a
choice, and all other things being equal, it would make sense to use
valaciclovir. Not the kind of message Novartis would like to hear.
Especially for a billion dollar blockbuster. And that, presumably, is
why they have sat on this data for the last six years (The Famvir
patent runs out in a couple of years).

More incredibly, even after all this time the researchers did not
actually get access to the original data. They were given cherry-
picked figues from a Novartis "in house review". They weren't allowed
to see the raw data that would allow them to make a more meaningful
comparison of the two drugs:

     Although we received data tables and listings for this study, we
were not able to obtain data tapes to verify the analyses and to
conduct what we consider the most clinically relevant analyses for
these types of data, such as the monthly frequency of recurrent
episodes or the frequency of days with lesions during the observation
period.


Does this sound familiar? I=92m sure it does to Aubrey Blumsohn.

So to sum up. We have data showing that a billion dollar drug is
inferior compared to another drug. This data doesn't get to see the
light of day for almost a decade, and even then, the researchers
aren't allowed to see the true figures. If that's not a scandal I
don't know what it. Presumably Novartis will plead "administrative
difficuties" caused by the company merger and transfer of Famvir data
to them from SKB. But I can bet if that trial had shown Famvir was
better than Valtrex the data would have been out there at the 2001
conferences "late breaking trial sessions", if not earlier.

So what we have here is a racket. A cover up. But instead of outrage,
these are the mild comments of Professor Ken Fife, of the department
of Infectious Diseases at the Indiana University School of Medicine.
Writing in the same STD journal he very generously gives Novartis the
benefit of the doubt:

     Novartis provided the authors with the study report and the data
listings, but not the primary data itself. Was the delay in the
release and publication of the study data a result of the corporate
shuffling and movement of responsibility for the study data created
by the sale of famciclovir? Alternatively, was it an effort to
suppress potentially unfavorable data? Should the full dataset have
been provided so that the authors could confirm the analysis and
perform additional analyses? Is Novartis to be criticized for
delaying and limiting the release of the study report? Alternatively,
should Novartis be praised for permitting potentially unfavorable
results to be published? The answers to these questions may depend on
one's view of the pharmaceutical industry.



Professor Fife's view of the pharmaceutical industry might be
coloured by the fact that he has received funding from both Novartis
and GSK.

posted by Michael Lascelles at 4:02 PM 2 comments

---------------------------------
James Love, CPTech / www.cptech.org / mailto:james.love@cptech.org /
tel. +1.202.332.2670 / mobile +1.202.361.3040

"If everyone thinks the same: No one thinks."  Bill Walton