Hepatitis C Drugs:

Hepatitis C is a viral disease that leads
to swelling (inflammation) of the liver.
About 170 million people worldwide are
chronically infected with hepatitis C,
including some 3.2 million Americans
who have the serious liver disease that
can lead to cirrhosis, liver cancer,
need for transplant or death if

The disease is spread primarily
through sharing of needles, such as
for illegal drugs and tattoos, or from
blood transfusions prior to standard
blood screening for the virus.

Currently, the best treatment for
hepatitis C is Pegylated Interferon +
Ribavirin. This cures about 75% of
patients with hepatitis C. The problem
is with Pegylated Interferon that it is
given by injection and there are many
side effects like dry eyes, depression,
nausea and thinning hair. Ribavirin is
taken orally.

Inhibitex  and Pharmasset both  now
have created a drug, INX-189 and PSI-
7977 respectively,   that so far looks
like it can take the place of interferon.
Both drugs are in clinical trials.

In December 2011 Bristol-Myers
Squibb Co. said  it will collaborate with
a unit of Johnson & Johnson to study a
potential combination therapy for
chronic hepatitis C.

The companies will study a regimen
that combines Johnson & Johnson's
drug TMC435 with Bristol-Myers
Squibb's daclatasvir (BMS-790052).
The clinical trial of the drug cocktail will
begin in the first half of 2012. It will
include a combination of the two drugs,
the drugs plus pegylated interferon
and ribavirin, and the drugs plus

Pegylated interferon and ribavirin have
been staples of hepatitis C treatment
for decades. Several drugmakers are
studying potential treatments that
could work without interferon, which is
given by IV and is associated with
particularly severe side effects. That
could allow patients to treat their
hepatitis C infections using only pills.
Some studies are testing experimental
drugs alone and without ribavirin.

In November 2011 Gilead Sciences
bought Pharmasset for $11 billion in
cash, vaulting Gilead into the lead to
develop the next generation of all-oral
hepatitis C therapies.

Pharmasset is developing oral drugs
for hepatitis C, or HCV, which is now  
treated by injections. Gilead made its
largest purchase ever after setbacks
with GS 6620, the company’s own
hepatitis C drug under development
which does not show much promise.

What Pharmasset has is potentially the
first all-oral hepatitis C treatment. The
company plans to apply for US
approval of its experimental drug, PSI-
7977, in the second half of 2013.  

Companies including Inhibitex Inc.  and
Achillion Pharmaceuticals Inc. are also
racing to develop medicines for the

Roche Holding AG, based in Basel,
Switzerland, agreed in October 2011 to
buy Anadys Pharmaceuticals Inc.,
another maker of experimental
medicines for hepatitis C.

Hepatitis C is a viral infection that can
lead to swelling of the liver. As many
as 170 million people globally carry the
virus, which is transmitted through
exposure to infected blood, and more
than 350,000 die from related illnesses
each year, according to  World Health

The hepatitis C market is currently
about $3 billion worldwide.

Earlier in 2011, Merck & Co. and
Vertex Pharmaceuticals Inc.  won
approval for the first new therapies for
hepatitis C in almost a decade.

In May 2011 FDA approved Incivek
(telaprevir) by Vertex Pharma.

Also in May 2011 FDA approved
Victrelis (boceprevir)  by Merck.

Vertex Pharmaceuticals Inc's  new
hepatitis C drug stormed out of the
gate, and as of July 2011 posting sales
of nearly $75 million in its first five
weeks on the market.

Incivek  is likely to become part of the
standard of care for hepatitis C and
widely expected to become a
multibillion-dollar seller.

More than 3,000 patients had started
therapy in the US with Incivek by mid-
July 2011 with a broad mix of
previously untreated patients and
those who failed to be cured by older

There had been speculation that
thousands of patients had been
delaying treatment in anticipation of
the new medicine and the early sales
figures appear to bear that out.

Vertex showed back in May 2011, in a
study of more than 1,000 patients, that
about three-fourths of people getting
their first round of treatment were
considered cured after getting Incivek
in combination with the standard meds.

Incivek prescriptions have been
outpacing Victrelis at a rate of better
than 3-to-1 in the early going, in 2011,
according to data compiled by Wolters
Kluwer's inThought unit.

Physicians are opting for the drug
that's easier to use and that's Incivek.

In trials, the Merck's Victrelis 48-week
treatment group, 66 percent of
patients achieved SVR (sustained
virologic response), and in the Victrelis
response-guided therapy group, 59
percent of patients achieved SVR,
compared to 21 percent of patients in
the control group.

SVR is defined as undetectable virus
levels in 24 weeks after the end of

The new drugs in combination with
older standard treatments have
demonstrated far higher cure rates
than the older medicines alone, as well
as the possibility of significantly shorter
treatment durations for many patients.

Vitamin D added to the standard
treatment protocol resulted in a
clearage of Hep C viruses at a rate of
A 96% success rate with plain old
vitamin D.
Less than 3 cents per day of vitamin D
to achieve this?
Here is an excerpt from  the research
at Rebecca Sieff Hospital in Safed and
Hillel Yaffeh Medical Center, Israel:

"A month after the start of treatment,
the virus had disappeared from the
blood in 44 percent of the group
receiving vitamin D supplements, as
opposed to just 18 percent among the
control group.
After three months, the success rate
for the group getting the supplement
rose to 96 percent, compared to 48
percent in the control group."

As of October 2011 Pharmasset's PSI-
7977, which belongs to a class of
compounds called nucleotide
analogues, will now be studied for 12
weeks as a single drug treatment,
while the other arm will test the drug in
combination with ribavirin.

In addition, a previously announced
arm of the trial has been modified to
an interferon-free 12-week regimen,
the company said in a statement.

Hepatitis C affects about 300 million
people worldwide, causing 8,000-
10,000 deaths each year due to
chronic liver disease caused by the

"The rapid and consistent antiviral
effects and high barrier to resistance
demonstrated with PSI-7977 to date
provided the rationale for additional
exploratory regimens in this setting,"
the company said.

In November 2011 Inhibitex of Georgia
said the dose of the drug, labeled INX-
189, was well tolerated, with no serious
side effects, when given to patients
with a certain form of chronic hepatitis
who have not been treated.

In Phase 2, the drug was administered
for seven days.

The Inhibitex drug INX-189 belongs to
the same "nucleoside" class of potent
oral hepatitis C drugs as Pharmasset's
heralded PSI-7977.

Inhibitex reported a 4.25 log drop in
Hep C viral load after 7 days of
treatment with a 200 mg dose of INX-
189 in treatment-naive patients. No
serious adverse events were reported.

That result is comparable to the viral
load decline demonstrated by
Pharmasset's PSI-7977 in an earlier

Nucleoside or "nucs" have become the
stars of the Hep C drug field because
of their potential as a backbone of
future all-oral combination Hep C
therapy. Pharmasset's nuc PSI-7977
has garnered the most attention, but
companies like Inhibitex and Idenix
Pharmaceuticals are also developing
their own Hep C nucs.

Analysts have called INX-189 a
promising treatment for Hepatitis C, a
disease that is expected to become a
larger public health problem as baby
boomers get older. Hepatitis C is the
primary cause of liver transplants in
the U.S.

In November 2011 the Pharmasset
investors were very nervous.
Pharmasset is currently starting its
Phase 3 trial of its hepatitis C drug PSI-
7977, which is very similar to Inhibitex'
INX-189. Both drugs are orally taken
and both take the place of interferon.
Pharmasset has a current market cap
of $5.2 billion. Upon successful
completion of its Phase 2 trials of INX-
189, it's likely that INHX will also have a
market cap in the billions. Currently,
it's only at $670 million.

As of July 2011 the following  HCV
drugs were some of the ones in

Company/ Molecule/ Mechanism/ Stage
1. Merck Victrelis (boceprevir) NS3/4A
protease inhibitor Approved
2. Vertex/J&J Incivek (telaprevir = VX-
750) NS3/4A protease inhibitor
3. Boehringer Ingelheim BI 201335
NS3/4A protease inhibitor Phase 3
4. Boehringer Ingelheim BI 207127
NS5B RNA-dep. polymerase inhibitor
5. Medivir/J&J TMC435 NS3/4A
protease inhibitor Phase 3
6. Anadys Setrobuvir Nonnucleoside
inhibitor of NS5B RNA-dep.
polymerase Ph.2b
7. Biolex Locteron Controlled-release
formulation of IFN-a2b Ph.2b
8. Pharmasset/Roche RG7128
Prodrug/cytidine nucleoside
mericitabine… PSI-6130 Ph.2b
9. Pharmasset PSI-7977 Pyrimidine
nucleotide polymerase inhibitor Ph.2b
10. Pharmasset PSI-938 Guanine
nucleotide polymerase inhibitor Phase
11. BMS PEG-IFN-A Type III IFN with
greater tissue selectivity than IFN-B Ph.
12. BMS BMS-790052 NS5A
replication complex inhibitor Phase 2
13. BMS BMS-650032 NS3/4A
protease inhibitor Phase 2
14. Abbott/Enanta ABT-450/r Protease
inhibitor + low-dose ritonavir Phase 2
15. Peregrine Pharmaceuticals
Bavituximab Targets
phosphatidylserine exposed on
surface of infected cells Phase 2

Johnson & Johnson has to decide how
to resolve the potential conflict in
selling both Medivir AB's and a
competitor's hepatitis C drugs if the
Swedish company's pill is approved,
Medivir's chief executive officer said.

Medivir is developing its TMC435
tablet with New Brunswick, New Jersey-
based J&J's Tibotec Pharmaceuticals
Ltd. unit. The Huddinge, Sweden-
based biotechnology company said  
the experimental treatment will get a
faster review from the U.S. Food and
Drug Administration. The medicine
may go on sale in late 2013.

ZymoGenetics also has a phase 2
hepatitis C drug. If pegylated-
interferon lambda can produce similar
results to Roche's Pegasys and
Merck's PegIntron with fewer side
effects, $735 million (paid by Bristol-
Myers for ZymoGenetics) is going to
look like a steal.

Achillion Pharmaceuticals has initiated
patient dosing in a Phase II clinical trial
of ACH-1625 for the treatment of
hepatitis C virus  infection. ACH-1625
is a potent small molecule inhibitor of
HCV protease, an enzyme necessary
for viral replication. The drug
candidate was discovered and is being
advanced by Achillion.

Idenix Pharmaceuticals  has good
news about  its HCV drug IDX-184.  
Patients on the 100 mg dose of ‘184
showed antiviral activity after 14 days
of treatment. The company is testing
several different doses of the drug for
safety and efficacy.

In October 2011 Anadys announced
agreement to be acquired by Roche.

Setrobuvir belongs to the "non-nuc"
class of direct-acting antiviral Hep C
drugs that has somewhat fallen out of
favor compared to the "nuc" class of
drugs exemplified by Pharmasset's PSI-

Setrobuvir, which to date has shown
potent antiviral activity and good
safety, is a polymerase inhibitor that
belongs to the chemical class of
compounds known as non-
nucleosides, which means that the
compound requires no activation within
the body prior to exerting its inhibitory
effect, and does not resemble
chemicals naturally found within the
human body. In other viral diseases
where non-nucleosides are used in
therapy, these attributes of non-
nucleosides have resulted in good
safety parameters and minimal
interference with the action of other
drugs. Anadys retains all rights to
setrobuvir, which was fully discovered
at the Company.

Setrobuvir's potency looks good
although the drug appears to work
more slowly than other drugs, which
could cause problems with higher rates
of viral breakthrough (or lower cure
rates) as patients are treated for
longer periods of time.

Anadys Pharmaceuticals  has been
attracting attention with the results of
its phase II study of the HCV drug
ANA598. The company says that 72%
of patients taking the 400 mg dose
twice daily plus the standard of care
showed undetectable levels of the
virus at eight weeks, compared to 38%
of people taking a placebo.

InterMune announced midstage data
on its HCV treatment danoprevir, also
known as ITMN-191. The drug is
partnered with Roche. The company
called the results "among the very best
reported by any DAA compound to
date," and expects that danoprevir will
“play a meaningful role in the
treatment of HCV patients.”

Biolex Therapeutics' lead product is
Locteron, a controlled release
formulation of interferon alpha for the
treatment of chronic hepatitis C.
OctoPlus licensed Locteron exclusively
to Biolex in October 2008. Locteron is
being manufactured for Biolex by
OctoPlus and is currently in Phase IIb
clinical studies.