Hepatitis C Protease Inhibitors
In this premature announcement to the public Vertex and Lilly tell us about a
protease inhibitor they are developing for HCV. Fortuneatly the article
describes what many researchers have known for 2 years, that developing a PI
for HCV is difficult. A number of researchers have felt we might not be able
to develop a PI for HCV. But several companies in addition to Vertex are in
development for such a PI. Perhaps one of these developers is further ahead
than Vertex and may enter clinical trials before Vertex. Little data has been
reported about any of these PIs. I'd like to see more data before hails are
reported in the financial press & the NY Times. Other potential HCV targets
appear to have more potential at this time and they are further along in
development. Several polymerase inhibitors are entering clinical studies. And
helicase inhibitors are being researched. As well, Heptazyme is an anti-HCV
drug in clinical trials now and will be explored in combination with
interferon. Several other new drugs are being researched including antisense.
As we know drug development is tricky. Often drugs fall by the wayside due to
toxicity or not working for one reason or another. Nonetheless, other
potential treatment or drugs are much further ahead in development than the
Vertex PI. Still, lets hope for the best.
"Hepatitis C Drug Said to Be Created"
NY Times, Jan 7
By ANDREW POLLACK
Vertex Pharmaceuticals (news/quote) and Eli Lilly are expected to announce
today that they have developed a drug candidate that can attack the hepatitis
C virus in the same way that several drugs attack H.I.V., the virus that
The companies say that their compound, which they hope to begin testing in
patients in 2003, blocks an enzyme known as a protease, which the hepatitis C
virus needs to replicate itself. Protease inhibitors for H.I.V. have had a
significant effect in treating AIDS, and many companies have tried to develop
one for hepatitis C.
But this has been difficult. "So far no one has succeeded," said Michael Lai,
a professor of
molecular microbiology and immunology at the University of Southern
California. But Dr. Lai
said he was not convinced that Vertex and Lilly had succeeded either, adding
that they had not published any data and had not begun human tests.
Joshua Boger, chief executive of Vertex, a biotechnology company in
Cambridge, Mass., said
the drug, which can be taken orally, seemed to work and was nontoxic in
laboratory and some
animal tests. But he said further animal tests were needed before human
testing could begin.
Dr. Boger said that he thought Vertex and Lilly were the first to announce a
hepatitis C protease inhibitor and that Vertex was receiving a $5 million
milestone payment from Lilly for the achievement.
But Charles M. Rice, executive and scientific director of the center for the
study of hepatitis C at Rockefeller University in New York, said he had
heard that other companies might also be close. Still other companies, he
said, were developing other ways to attack the virus.
"We're getting pretty excited about some of these new compounds that are
entering into clinical trials," he said. "It's kind of like when the first
protease and reverse transcriptase inhibitors were hitting the clinic for
Biotechnology companies like Vertex typically announce every nugget of
progress to attract
investors. Indeed, the company's announcement coincides with the start today
of the J. P.
Morgan H&Q health care conference in San Francisco. Larger drug companies do
discuss compounds until they reach later-stage clinical trials. A spokesman
(news/quote), for instance, said his company also had a protease inhibitor
candidate that was not in clinical trials.
About four million Americans have been infected with hepatitis C, which is
infected blood or needles. The virus can lead to cirrhosis or liver cancer.
The main treatment now is the combination of alpha interferon and ribavirin,
scientists think works by stimulating the immune system to attack the virus.
But the drugs work
in only about half of the cases, so the search has been on for drugs that
attack the virus directly.
Vertex specializes in structure- based drug design. Instead of trying
thousands of compounds to see which one can bind to the intended target, it
first determines the three-dimensional shape of the target and then tries to
design a drug to mesh with it like a glove on a hand.
It has taken Vertex five years since determining the structure of the
hepatitis C protease in 1996 to design a molecule that can bind to it.
The problem is the unusual shape of the protease. Most targets have various
nooks and crannies
to which the drug can cling. The H.I.V. protease, for instance, had a deep
hole in it. But the
surface of the hepatitis C protease is practically flat, with only the
"Instead of stuffing a bomb in a cave, which is what the H.I.V. protease
inhibitor does, it's like
climbing a sheer rock face," said Dr. Boger of Vertex, which developed Age
nerase, one of the
H.I.V. protease inhibitors on the market. "In my nearly 25 years in the
industry, this is the most
difficult drug design problem that I've ever encountered."