Roche's investigational therapy
for chronic hepatitis C virus (HCV) infection, R1626, has shown a
significant end-of-treatment response rate when given in combination with
PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin). R1626 also
shows a high barrier to the development of resistance.
After four weeks of treatment with this triple combination, followed by
44 weeks of PEGASYS and COPEGUS, levels of HCV were undetectable in 84
percent of patients infected with genotype 1 virus. This was higher than
patients treated with PEGASYS and COPEGUS alone for the entire 48-week
treatment period (65 percent). These new data were presented in a
late-breaker oral session at the 43rd Annual Meeting of the European
Association for the Study of the Liver (EASL), being held in Milan, Italy.
R1626 was discovered and developed at Roche and belongs to a class of
antivirals called polymerase inhibitors, which are being investigated with
the current standard of care for hepatitis C combination therapy with
pegylated interferon and ribavirin.
"These results demonstrate that R1626 holds significant promise to
potentially increase the number of hepatitis C patients who can be
successfully treated," said Dr. David Nelson, Director of Hepatology and
Liver Transplantation at the University of Florida, Gainesville, Florida.
"Since most patients responded very early in treatment with R1626, we
expect sustained virological response (SVR) rates that improve
significantly on those achieved with the current standard of care. I look
forward to SVR data from this Phase IIa study, and to results of the
ongoing Phase IIb study."
Patients in this Phase IIa study will be followed for an additional 24
weeks with no treatment to determine the SVR rate, which indicates
successful treatment.
More About the Phase IIa Study and End-of-Treatment Results
The Phase IIa study is a multicenter trial that enrolled 104 patients
with genotype 1 HCV, who had not previously received treatment. Its primary
endpoint was to evaluate the four-week efficacy and safety of combining
R1626 with PEGASYS alone or with PEGASYS plus COPEGUS, in comparison to a
current HCV standard of care (SOC), pegylated interferon plus ribavirin.
Patients were randomized into the following treatment groups:
-- Group A: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly for
four weeks
-- Group B: R1626 3,000 mg twice a day plus PEGASYS 180 mcg weekly for
four weeks
-- Group C: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly plus
COPEGUS 1,000/1,200 mg daily for four weeks
-- Group D (standard of care group): PEGASYS 180 mcg weekly plus COPEGUS
1,000/1,200 mg daily for four weeks
Following the four weeks of treatment in this study, all patients
received PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for an
additional 44 weeks to complete the 48-week trial.
The study found:
-- Data collected at four weeks showed that patients receiving the triple
combination (Group C) had a mean decrease in viral load of 5.2 log10
from baseline, indicating a robust and rapid virological response.
-- At week 48, HCV was undetectable in 84 percent of patients (26 of 31)
who received the triple combination of R1626 1,500 mg BID + PEGASYS +
COPEGUS compared with 65 percent of patients (13 of 20) treated with
the SOC.
-- A higher incidence of grade four neutropenia was reported in the R1626
treatment arms during the four-week treatment period; however, after
stopping treatment with R1626, absolute neutrophil counts returned to
the level typically seen with patients receiving the SOC alone.
R1626 - A High Barrier to the Development of Resistance
In a separate oral presentation at EASL, it was reported that R1626
continues to present a high barrier to the development of viral resistance.
This is a serious concern emerging in the development of small molecule
treatments for hepatitis C. Resistance to R1626 has not been yet been
identified, after either two weeks of R1626 monotherapy, or after four
weeks in patients treated with R1626 in combination therapy.
Rapid Development of R1626 - A Large Phase IIb Study is Now Fully
Enrolled
A large Phase IIb study with R1626 was initiated in November 2007 to
define the optimal dose of R1626, in combination with PEGASYS and COPEGUS.
This Phase IIb trial, called POLI 1, is now fully enrolled with
approximately 500 patients, all with genotype 1 hepatitis C.
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and a
leading cause of cirrhosis, liver cancer and the need for liver
transplants. According to the Centers for Disease Control and Prevention
(CDC), an estimated 4.1 million Americans (1.6 percent) have been infected
with hepatitis C; 3.2 million are chronically infected. The number of new
infections per year has declined from an average of 240,000 in the 1980s to
about 26,000 in 2004. CDC estimates the number of hepatitis C-related
deaths could increase to 38,000 annually by the year 2010, surpassing
annual HIV/AIDS deaths.
About PEGASYS
PEGASYS, in combination with COPEGUS (ribavirin), are indicated for the
treatment of adults with chronic hepatitis C who have compensated liver
disease and have not previously been treated with interferon alpha.
Efficacy has been demonstrated in patients with compensated liver disease
and histological evidence of cirrhosis (Child-Pugh class A) and patients
with HIV disease that are clinically stable (e.g., antiretroviral therapy
not required or receiving stable antiretroviral therapy). In addition,
PEGASYS in combination with COPEGUS is the first and only FDA-approved
regimen for the treatment of chronic hepatitis C in patients coinfected
with hepatitis C and HIV. PEGASYS is the only pegylated interferon
indicated for the treatment of adult patients with chronic hepatitis B
(HBeAg positive and HBeAg negative chronic hepatitis B who have compensated
liver disease and evidence of viral replication and liver inflammation).
PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a
week. COPEGUS is available as a 200mg tablet, and is administered orally
two times a day as a split dose. Roche has backed PEGASYS with the most
extensive clinical research program ever undertaken in hepatitis C, with
major studies initiated to advance treatment for hepatitis C patients with
unmet needs, including patients co-infected with HIV and HCV, African
Americans, patients with cirrhosis, and patients who have failed to respond
to previous therapy.
IMPORTANT SAFETY INFORMATION
PEGASYS, alone or in combination with COPEGUS, is indicated for the
treatment of adults with chronic hepatitis C virus infection who have
compensated liver disease and have not been previously treated with
interferon alpha. Patients in whom efficacy was demonstrated included
patients with compensated liver disease and histological evidence of
cirrhosis (Child-Pugh class A).
Alpha interferons, including PEGASYS(R) (Peginterferon alfa-2a), may
cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune,
ischemic, and infectious disorders. Patients should be monitored closely
with periodic clinical and laboratory evaluations. Therapy should be
withdrawn in patients with persistently severe or worsening signs or
symptoms of these conditions. In many, but not all cases, these disorders
resolve after stopping PEGASYS therapy (see CONTRAINDICATIONS, WARNINGS,
PRECAUTIONS and ADVERSE REACTIONS in complete product information).
Use with Ribavirin. Ribavirin, including COPEGUS(R), may cause birth
defects and/or death of the fetus. Extreme care must be taken to avoid
pregnancy in female patients and in female partners of male patients.
Ribavirin causes hemolytic anemia. The anemia associated with ribavirin
therapy may result in a worsening of cardiac disease. Ribavirin is
genotoxic and mutagenic and should be considered a potential carcinogen
(see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in
complete product information).
PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS
or any of its components, autoimmune hepatitis, and hepatic decompensation
(Child-Pugh score greater than 6; class B and C) in cirrhotic CHC
monoinfected patients before or during treatment. PEGASYS is also
contraindicated in hepatic decompensation with Child-Pugh score greater
than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or
during treatment. PEGASYS is also contraindicated in neonates and infants
because it contains benzyl alcohol. Benzyl alcohol is associated with an
increased incidence of neurological and other complications in neonates and
infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is
additionally contraindicated in patients with a hypersensitivity to COPEGUS
or any of its components, in women who are pregnant, men whose female
partners are pregnant, and patients with hemoglobinopathies (eg,
thalassemia major, sickle-cell anemia).
COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE
PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF
THERAPY. Women of childbearing potential and men must use two forms of
effective contraception during treatment and during the 6 months after
treatment has concluded. Routine monthly pregnancy tests must be performed
during this time. If pregnancy should occur during treatment or during 6
months post-therapy, the patient must be advised of the significant
teratogenic risk of COPEGUS therapy to the fetus.
Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of
hepatic decompensation and death when treated with alpha interferons,
including PEGASYS. During treatment, patients' clinical status and hepatic
function should be closely monitored, and PEGASYS treatment should be
immediately discontinued if decompensation (Child-Pugh score greater than
or equal to 6) is observed. Ischemic and hemorrhagic cerebrovascular events
have been observed in patients treated with interferon alfa-based
therapies, including PEGASYS. Events occurred in patients with few or no
reported risk factors for stroke, including patients less than 45 years of
age. Because these are spontaneous reports, estimates of frequency cannot
be made and causal relationship between interferon alfa-based therapies and
these events is difficult to establish.
The most common adverse events reported for PEGASYS and COPEGUS
combination therapy observed in clinical trials were fatigue/asthenia
(65%), headache (43%), pyrexia (41%), myalgia (40%),
irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%),
neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%),
injection site reaction (23%), arthralgia (22%), depression (20%), pruritus
(19%) and dermatitis (16%).
Serious adverse events in hepatitis C trials included neuropsychiatric
disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide,
psychotic disorder and hallucinations), serious and severe bacterial
infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic
anemia), cardiovascular disorders (hypertension, supraventricular
arrhythmias and myocardial infarction), hypersensitivity (including
anaphylaxis), endocrine disorders (including thyroid disorders and diabetes
mellitus), autoimmune disorders (including idiopathic thrombocytopenic
purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid
arthritis and interstitial nephritis), pulmonary disorders (dyspnea,
pneumonia, bronchiolitis obliterans, interstitial pneumonitis and
sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis),
pancreatitis, and ophthalmologic disorders (decrease or loss of vision,
retinopathy including macular edema and retinal thrombosis/hemorrhages,
optic neuritis and papilledema). Adverse reactions reported during
post-approval use of PEGASYS therapy, with and without ribavirin, include
hearing impairment, hearing loss, serious skin reactions, including
erythema multiforme major, and infections (bacterial, viral and fungal).
for chronic hepatitis C virus (HCV) infection, R1626, has shown a
significant end-of-treatment response rate when given in combination with
PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin). R1626 also
shows a high barrier to the development of resistance.
After four weeks of treatment with this triple combination, followed by
44 weeks of PEGASYS and COPEGUS, levels of HCV were undetectable in 84
percent of patients infected with genotype 1 virus. This was higher than
patients treated with PEGASYS and COPEGUS alone for the entire 48-week
treatment period (65 percent). These new data were presented in a
late-breaker oral session at the 43rd Annual Meeting of the European
Association for the Study of the Liver (EASL), being held in Milan, Italy.
R1626 was discovered and developed at Roche and belongs to a class of
antivirals called polymerase inhibitors, which are being investigated with
the current standard of care for hepatitis C combination therapy with
pegylated interferon and ribavirin.
"These results demonstrate that R1626 holds significant promise to
potentially increase the number of hepatitis C patients who can be
successfully treated," said Dr. David Nelson, Director of Hepatology and
Liver Transplantation at the University of Florida, Gainesville, Florida.
"Since most patients responded very early in treatment with R1626, we
expect sustained virological response (SVR) rates that improve
significantly on those achieved with the current standard of care. I look
forward to SVR data from this Phase IIa study, and to results of the
ongoing Phase IIb study."
Patients in this Phase IIa study will be followed for an additional 24
weeks with no treatment to determine the SVR rate, which indicates
successful treatment.
More About the Phase IIa Study and End-of-Treatment Results
The Phase IIa study is a multicenter trial that enrolled 104 patients
with genotype 1 HCV, who had not previously received treatment. Its primary
endpoint was to evaluate the four-week efficacy and safety of combining
R1626 with PEGASYS alone or with PEGASYS plus COPEGUS, in comparison to a
current HCV standard of care (SOC), pegylated interferon plus ribavirin.
Patients were randomized into the following treatment groups:
-- Group A: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly for
four weeks
-- Group B: R1626 3,000 mg twice a day plus PEGASYS 180 mcg weekly for
four weeks
-- Group C: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly plus
COPEGUS 1,000/1,200 mg daily for four weeks
-- Group D (standard of care group): PEGASYS 180 mcg weekly plus COPEGUS
1,000/1,200 mg daily for four weeks
Following the four weeks of treatment in this study, all patients
received PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for an
additional 44 weeks to complete the 48-week trial.
The study found:
-- Data collected at four weeks showed that patients receiving the triple
combination (Group C) had a mean decrease in viral load of 5.2 log10
from baseline, indicating a robust and rapid virological response.
-- At week 48, HCV was undetectable in 84 percent of patients (26 of 31)
who received the triple combination of R1626 1,500 mg BID + PEGASYS +
COPEGUS compared with 65 percent of patients (13 of 20) treated with
the SOC.
-- A higher incidence of grade four neutropenia was reported in the R1626
treatment arms during the four-week treatment period; however, after
stopping treatment with R1626, absolute neutrophil counts returned to
the level typically seen with patients receiving the SOC alone.
R1626 - A High Barrier to the Development of Resistance
In a separate oral presentation at EASL, it was reported that R1626
continues to present a high barrier to the development of viral resistance.
This is a serious concern emerging in the development of small molecule
treatments for hepatitis C. Resistance to R1626 has not been yet been
identified, after either two weeks of R1626 monotherapy, or after four
weeks in patients treated with R1626 in combination therapy.
Rapid Development of R1626 - A Large Phase IIb Study is Now Fully
Enrolled
A large Phase IIb study with R1626 was initiated in November 2007 to
define the optimal dose of R1626, in combination with PEGASYS and COPEGUS.
This Phase IIb trial, called POLI 1, is now fully enrolled with
approximately 500 patients, all with genotype 1 hepatitis C.
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and a
leading cause of cirrhosis, liver cancer and the need for liver
transplants. According to the Centers for Disease Control and Prevention
(CDC), an estimated 4.1 million Americans (1.6 percent) have been infected
with hepatitis C; 3.2 million are chronically infected. The number of new
infections per year has declined from an average of 240,000 in the 1980s to
about 26,000 in 2004. CDC estimates the number of hepatitis C-related
deaths could increase to 38,000 annually by the year 2010, surpassing
annual HIV/AIDS deaths.
About PEGASYS
PEGASYS, in combination with COPEGUS (ribavirin), are indicated for the
treatment of adults with chronic hepatitis C who have compensated liver
disease and have not previously been treated with interferon alpha.
Efficacy has been demonstrated in patients with compensated liver disease
and histological evidence of cirrhosis (Child-Pugh class A) and patients
with HIV disease that are clinically stable (e.g., antiretroviral therapy
not required or receiving stable antiretroviral therapy). In addition,
PEGASYS in combination with COPEGUS is the first and only FDA-approved
regimen for the treatment of chronic hepatitis C in patients coinfected
with hepatitis C and HIV. PEGASYS is the only pegylated interferon
indicated for the treatment of adult patients with chronic hepatitis B
(HBeAg positive and HBeAg negative chronic hepatitis B who have compensated
liver disease and evidence of viral replication and liver inflammation).
PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a
week. COPEGUS is available as a 200mg tablet, and is administered orally
two times a day as a split dose. Roche has backed PEGASYS with the most
extensive clinical research program ever undertaken in hepatitis C, with
major studies initiated to advance treatment for hepatitis C patients with
unmet needs, including patients co-infected with HIV and HCV, African
Americans, patients with cirrhosis, and patients who have failed to respond
to previous therapy.
IMPORTANT SAFETY INFORMATION
PEGASYS, alone or in combination with COPEGUS, is indicated for the
treatment of adults with chronic hepatitis C virus infection who have
compensated liver disease and have not been previously treated with
interferon alpha. Patients in whom efficacy was demonstrated included
patients with compensated liver disease and histological evidence of
cirrhosis (Child-Pugh class A).
Alpha interferons, including PEGASYS(R) (Peginterferon alfa-2a), may
cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune,
ischemic, and infectious disorders. Patients should be monitored closely
with periodic clinical and laboratory evaluations. Therapy should be
withdrawn in patients with persistently severe or worsening signs or
symptoms of these conditions. In many, but not all cases, these disorders
resolve after stopping PEGASYS therapy (see CONTRAINDICATIONS, WARNINGS,
PRECAUTIONS and ADVERSE REACTIONS in complete product information).
Use with Ribavirin. Ribavirin, including COPEGUS(R), may cause birth
defects and/or death of the fetus. Extreme care must be taken to avoid
pregnancy in female patients and in female partners of male patients.
Ribavirin causes hemolytic anemia. The anemia associated with ribavirin
therapy may result in a worsening of cardiac disease. Ribavirin is
genotoxic and mutagenic and should be considered a potential carcinogen
(see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in
complete product information).
PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS
or any of its components, autoimmune hepatitis, and hepatic decompensation
(Child-Pugh score greater than 6; class B and C) in cirrhotic CHC
monoinfected patients before or during treatment. PEGASYS is also
contraindicated in hepatic decompensation with Child-Pugh score greater
than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or
during treatment. PEGASYS is also contraindicated in neonates and infants
because it contains benzyl alcohol. Benzyl alcohol is associated with an
increased incidence of neurological and other complications in neonates and
infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is
additionally contraindicated in patients with a hypersensitivity to COPEGUS
or any of its components, in women who are pregnant, men whose female
partners are pregnant, and patients with hemoglobinopathies (eg,
thalassemia major, sickle-cell anemia).
COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE
PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF
THERAPY. Women of childbearing potential and men must use two forms of
effective contraception during treatment and during the 6 months after
treatment has concluded. Routine monthly pregnancy tests must be performed
during this time. If pregnancy should occur during treatment or during 6
months post-therapy, the patient must be advised of the significant
teratogenic risk of COPEGUS therapy to the fetus.
Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of
hepatic decompensation and death when treated with alpha interferons,
including PEGASYS. During treatment, patients' clinical status and hepatic
function should be closely monitored, and PEGASYS treatment should be
immediately discontinued if decompensation (Child-Pugh score greater than
or equal to 6) is observed. Ischemic and hemorrhagic cerebrovascular events
have been observed in patients treated with interferon alfa-based
therapies, including PEGASYS. Events occurred in patients with few or no
reported risk factors for stroke, including patients less than 45 years of
age. Because these are spontaneous reports, estimates of frequency cannot
be made and causal relationship between interferon alfa-based therapies and
these events is difficult to establish.
The most common adverse events reported for PEGASYS and COPEGUS
combination therapy observed in clinical trials were fatigue/asthenia
(65%), headache (43%), pyrexia (41%), myalgia (40%),
irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%),
neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%),
injection site reaction (23%), arthralgia (22%), depression (20%), pruritus
(19%) and dermatitis (16%).
Serious adverse events in hepatitis C trials included neuropsychiatric
disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide,
psychotic disorder and hallucinations), serious and severe bacterial
infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic
anemia), cardiovascular disorders (hypertension, supraventricular
arrhythmias and myocardial infarction), hypersensitivity (including
anaphylaxis), endocrine disorders (including thyroid disorders and diabetes
mellitus), autoimmune disorders (including idiopathic thrombocytopenic
purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid
arthritis and interstitial nephritis), pulmonary disorders (dyspnea,
pneumonia, bronchiolitis obliterans, interstitial pneumonitis and
sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis),
pancreatitis, and ophthalmologic disorders (decrease or loss of vision,
retinopathy including macular edema and retinal thrombosis/hemorrhages,
optic neuritis and papilledema). Adverse reactions reported during
post-approval use of PEGASYS therapy, with and without ribavirin, include
hearing impairment, hearing loss, serious skin reactions, including
erythema multiforme major, and infections (bacterial, viral and fungal).
Комментариев нет:
Отправить комментарий