HCV
Advocate easl 2007 News Review
EASL 2007 Index
Update -
Hepatitis C
·
Vertex to meet Hepatitis C patients needs?
Hepatitis B
·
Entecavir shows low incidence of
resistance in hep B patients
Download PDF version of this News Review:
Sustained
Response to Anti-Hepatitis C Virus Drugs Results in Cure in Virtually All
Cases: Presented at EASL
By Jill Stein
BARCELONA, SPAIN -- April 16,
2007 -- More than 99% of patients infected with hepatitis C virus (HCV) who
achieve a sustained virological response (SVR) have an outcome that may be
considered a cure, according to data presented here at the 42nd Annual Meeting
of the European Association for the Study of the Liver (EASL).
Lead investigator Mark G.
Swain, MD, professor of medicine, University of Calgary, Calgary, Canada, said
that only 8 of 997 patients who achieved an SVR later developed re-infection.
Dr. Swain and colleagues
reviewed the long-term outcomes from nine studies and identified patients who
had achieved a SVR after treatment with alpha peginterferon alfa-2a (40 KD)
(Pegasys(R)) as monotherapy or in combination with ribavirin (Copegus(R)).
"I tell my patients who
have had a sustained virological response that they can go home and get on with
their lives," Dr. Swain said in a presentation on April 12th. "I tell
them that there is less than a 0.5% chance that the disease will ever
return."
The study included three
trials in which patients were treated with monotherapy and six trials in which
the combination treatment was used. The combination therapy is now considered
the treatment standard, and as many as 66% of HCV patients who take their
antiviral medication as prescribed -- usually for 48 weeks -- are able to
achieve the SVR.
A SVR was defined as an
undetectable viral load in the blood six months following cessation of
treatment.
Dr. Swain noted that
statistical analyses on this study were not performed. "We were looking
for an absolute number," he said. "There was no comparator
group."
Of patients who achieved a SVR,
163 patients who had HCV monoinfection were treated with peginterferon alfa-2a
alone; 741 patients with HCV monoinfection were treated with peginterferon
alfa-2a plus ribavirin in combination; 93 patients co-infected with HIV and HCV
were treated with either monotherapy or combination therapy.
"We found that a
sustained virological response is a sustained virological response whether it
occurs in an immunosuppressed patient due to disease such as HIV or in a
patient who has undergone transplantation and requires immunosuppressive
drugs," Dr. Swain said. "There was no falloff in response."
Because of the study's
methodology, it will be impossible to determine if patients indeed relapsed or
were re-infected, he added.
The study was supported by
Roche.
[Presentation title: Durable
Sustained Virological Response After Treatment With Peginterferon a-2a
(PEGYSUS) or in Combination With Ribavarin (COPEGUS): 5-Year Follow-Up and the
Criteria of a Cure. Abstract Number 1]
Vertex
to meet Hepatitis C patients needs?
By Dr Matt Wilkinson
17/04/2007 - Vertex
Pharmaceuticals has released early results on its first-in-class hepatitis C drug
that show it has the potential to shorten treatment times for those suffering
from the hard-to-treat genotype-1.
The results of a Phase II
trial of Vertex' protease inhibitor, telaprevir (VX-950), showed the drug, in
combination with Roche's pegylated interferon Pegasys (peginterferon alfa-2a;
peg-IFN) and ribavirin (RBV) enabled some patients to clear the virus in 12
weeks.
According to the World Health
Organisation (WHO), the hepatitis C virus (HCV) is a major cause of acute
hepatitis and chronic liver diseases such as cirrhosis and liver cancer. It is
estimated that there are over 170m chronic sufferers worldwide, fuelling the
HCV treatment market to over $2.3bn (€1.7bn) in 2004.
The latest results from the
trial, dubbed PROVE 1, were released at the Annual Meeting of the European
Association for the Study of the Liver (EASL) last week and offer new hope to
sufferers of genotype-1 HCV - the most
difficult to treat and the most prevalent strain in the US, western Europe and
Japan.
While treatments for hepatitis
B have met with considerable success, sufferers of HCV have not been so
fortunate given the limited effectiveness of the two drugs available to them,
peg-IFN and RBV.
HCV has evolved over thousands
of years to produce six genotypes and many subgroups, with genotypes 1 and 4
being not as responsive to interferon treatments that can take a year. This is
twice as long as typical treatment times for genotypes 2 and 3.
Genotypes 1, 2 and 3 are most commonly
found in Europe and the US, whereas genotypes 4 and 5 are most prevalent in
Africa.
The company has previously
stated its intentions to develop the drug as both a monotherapy and in
combination with peg-IFN and RBV as in the current study which showed that the
treatment was generally well tolerated and had a high rate of rapid viral
response (RVR) and a low rate of on-treatment viral breakthrough.
Many of the current treatment
regimens fail and lead to relapse. The treatments are often not well tolerated
with patients suffering from severe side effects.
Vertex has also initiated a
Phase IIb trial (PROVE 3) to study the effects of the drug on genotype-1 HCV
patients who have not achieved a sustained viral response (SVR) with previous
interferon-based treatments.
If PROVE 3 is successful the
treatment could offer hope to those patients that are unresponsive to peg-INF
and RBV as there is currently a lack of alternative treatments with very few
sufferers achieving a sustained viral load reduction upon retreatment.
One major problem in stemming
HCV transmission is that the virus can go undetected for up to 20 years after
the initial infection.
The US National Foundation for
Infectious Diseases believes that complications from HCV are now the leading
reason for liver transplants and account for nearly 2000 liver transplants a
year. Any drug that can help cure the disease would reduce this number
significantly.
Competition
After a long dearth of
potential drugs in companies' pipelines there is now a lot of activity in the
area after recent technical advances in cell culture systems and replication
assays have led to mechanistic discoveries of HCV infection allowing the
discovery of various new potential antiviral targets.
There are two HCV protease inhibitors
that are competing with telaprevir to be the first on the market, namely
Schering-Plough's SCH503034, which is also in Phase II, and Roche / Intermune's
ITMN-191, which is in early clinical trials. Schering-Plough has stated they
believe that SCH503034 has the potential to be a multibillion dollar drug.
There are also three
polymerase inhibitors currently in Phase II trials: Idenix/Novartis'
valopicitabine (NM283), ViroPharma's HCV-796 and Roche's R1626.
Roche/Idenix are also
investigating valtorcitabine (val-LdC) - a first strand viral DNA synthesis
inhibitor in Phase II HCV trials after initial success as an HBV treatment.
Entecavir shows low incidence of resistance
in hep B patients
Bristol-Myers Squibb Company
announced new results of the Baraclude (entecavir) resistance monitoring
programme, which found a continued low incidence of resistance in studies of
nucleoside-naive chronic hepatitis B patients through four years of treatment
(n=663). In the three nucleoside- naive studies analyzed, two patients, or less
than one per cent, experienced virologic breakthrough due to Baraclude
resistance through the third year, and no additional patients developed
resistance in the fourth year. In lamivudine- refractory patients, virologic
breakthrough due to Baraclude resistance occurred in 15 per cent (n=8/53) of
patients during year four.
The study results were presented at the
42nd Annual Meeting of the European Association for the Study of Liver Diseases
(EASL) in Barcelona, Spain.
Drug resistance occurs when a virus
mutates to avoid the effects of the medication. This can make treatment of
hepatitis B challenging, because it can decrease the efficacy of the current
medication and may compromise future treatment options. To date, studies have
shown that multiple mutations are required to develop Baraclude resistance.
"The low incidence of resistance
seen in nucleoside-naive patients through four years of treatment reflects
Baraclude's high barrier to resistance in this patient population," said
Richard Colonno, Ph.D., vice president for virology drug discovery at
Bristol-Myers Squibb.
More than 700 patients across six
studies initiated therapy on Baraclude (entecavir) and were monitored for
treatment response and resistance.
The year four analysis evaluated
those patients who received treatment with Baraclude during the fourth year
(n=120 for patients in nucleoside-naive studies and n=53 for patients in
lamivudine-refractory studies). In this comprehensive analysis, all patients
enrolled in Bristol-Myers Squibb clinical trials ETV-014, -015, -022, -027,
-026 and -901 who experienced a virologic breakthrough (greater than or equal
to one log increase in HBV DNA from nadir as measured by a common assay -
polymerase chain reaction or PCR), or whose virus had not yet reached
undetectable levels - a measurement of the levels of hepatitis B virus in the
blood (HBV DNA levels >300 copies/mL by PCR assay) at weeks 48, 96, 144, 192
or end of dosing were sequenced to determine if any changes occurred in the
genetic code of the virus that would result in resistance or loss of
effectiveness of Baraclude.
Viral load reduction in chronic hepatitis
B patients treated with Baraclude in nucleoside-naive and lamivudine-refractory
studies was also evaluated.