Monday, November 1, 2010

2010/Telaprevir/Boceprevir SVR all Trials *geno 1,2,3


Telaprevir and Boceprevir

This is a summary of SVR results treating Hepatitis C using current available data from new and previous trials . Included is an older trial with telaprevir in genotype 2 and 3 patients*small study and new data on genotype 1 patients coming from the AASLD meeting this week. This triple therapy is used with telaprevir or boceprevir in combination with Pegylated interferon and Ribavirin.
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.*data and conclusions should be considered to be preliminary until published in a peer-reviewed journal
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Here is a quick and easy breakdown of the trials ..
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Telaprevir:
The two trials named "ADVANCE and ILLUMINATE" were for patients with genotype 1 who never treated before. "The Phase 3 ILLUMINATE trial was designed to confirm both the use of response-guided therapy and to evaluate whether there was any benefit to extending total treatment duration from 24 to 48 weeks." (Never Treated Before)
In the trial named "REALIZE" genotype 1 patients did treat before with *SOC but did not achieve a cure. (Failed Treatment)
The new trial will be called the "OPTIMIZE" and is for genotype 1 patients who have not previously treated. (Never Treated Before).

Boceprevir:
SPRINT-2 trial- genotype 1 - (Never Treated Before)
RESPOND-2 trial - genotype 1 - previously treated but did not respond to or relapsed after treatment. (Failed Treatment) or treatment failed you..
More Detailed Information On these Trials Below.

Telaprevir
Telaprevir is an investigational oral protease inhibitor (PI) for the treatment of hepatitis C virus (HCV) infection. HCV protease is a unique HCV enzyme that plays a key role in viral replication and may also help the virus evade host immune defenses. Telaprevir is the first hepatitis C drug currently in development that has demonstrated activity in patients who have failed prior therapy.
.BoceprevirCurrently approved treatments for chronic HCV infection are designed to boost the host's immune response to help eradicate the virus. In contrast, boceprevir is designed to directly attack the virus by inhibiting protease enzymes that are critical to HCV replication. Clinical studies suggest that it is a potent addition to standard therapies in patients with HCV
genotype-1, the most common and hardest form of HCV to treat.
.Updates From The AASLD @ CCO: From Podium to Practice: Updates in HCV Treatment
From Podium to Practice: Updates in HBV Treatment

*See links for complete trial data; number of participants, dose, length of treatment, special considerations, side effects, and treatment arms. .

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SVR= defined as undetectable virus levels 24 weeks after the end of treatment
SOC= standard of care
Control groups= did not receive boceprevir but only "Peg/riba plus placebo."
RGT = Response-guided therapy

What treatment is FDA approved and used currently to treat HCV ?...
Pegylated interferon/ribavirin is used as the current standard of care (SOC) therapy for hepatitis c treatment.
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.What is the success rate or SVR treating with "SOC"= standard of care ?
If you have genotype 1 or 4 you are generally given 12 months of treatment and have about a 50% chance of a cure. If you have genotypes 2 or 3 you are generally given six months of treatment and have a 70–80% chance of a cure.

Telaprevir
What about treating with telaprevir in combination with Pegylated interferon and Ribavirin in Genotype 2 and 3 patients who "Have Never Treated Before" ?
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From The : Association for the Study of the Liver (EASL 2010)
05/14/10
*Treating with telaprevir without pegylated interferon (small study)
.49 previously untreated participants with genotype 2 or 3 chronic hepatitis C were randomly assigned to receive telaprevir alone (750 mg every 8 hours),
telaprevir with pegylated interferon alfa-2a (Pegasys) plus 800 mg ribavirin,
or pegylated interferon/ribavirin with placebo for 2 weeks.
All participants then received pegylated interferon/ribavirin through week 24 (the standard duration of treatment for these genotypes).

Geno 2Genotype 2 telaprevir alone: SVR 56%;
Genotype 2 telaprevir/pegylated interferon/ribavirin: SVR 100%;
Genotype 2 pegylated interferon/ribavirin: SVR 89%.

Geno 3Genotype 3 telaprevir alone: SVR 50%;
Genotype 3 telaprevir and pegylated interferon/ribavirin: SVR 67%;
Genotype 3 pegylated interferon/ribavirin: SVR 44%..

Genotype 2 is more responsive than genotype 3 here and also in SOC= Standard of Care.

Boceprevir
.What about treating with boceprevir and pegylated interferon/ribavirin in genotype 2 and 3 in patients who "Have Never Treated Before "?

No Information.........

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What about treating with telaprevir in combination with pegylated interferon/ribavirin in genotype 1 patients who have "Never treated before"?

(ADVANCE and ILLUMINATE) : Together, these studies enrolled people with genotype 1 hepatitis C who "had not been treated" for their disease previously

A fact sheet on the Phase 3 telaprevir development program is available at http://www.vrtx.com/aasld2010.html

Results from ADVANCE & ILLUMINATE

Overall in ADVANCE, 75% of people treated with a telaprevir-based combination regimen for 12 weeks, followed by an additional 12 or 36 weeks of pegylated-interferon and ribavirin alone, achieved SVR, compared to 44% of people treated with 48 weeks of pegylated-interferon and ribavirin alone.

New data from this study showed that 62% of African Americans/Blacks achieved SVR with telaprevir compared to 25% of African Americans/Blacks who were treated with pegylated-interferon and ribavirin alone. Additionally, 62% of people with advanced liver fibrosis or cirrhosis (scarring of the liver) achieved SVR with telaprevir compared to 33% who were treated with pegylated-interferon and ribavirin alone.

Response-guided therapy was used in ADVANCE, whereby patients whose virus was undetectable at weeks 4 and 12 of treatment with telaprevir-based therapy were eligible to reduce their treatment time by half – from 48 weeks to 24 weeks.

ILLUMINATE was designed to confirm both the use of response-guided therapy and to evaluate whether there was any benefit in extending therapy from 24 weeks to 48 weeks in people who met these criteria. In ADVANCE and ILLUMINATE, 58% and 65% of people, respectively, met these criteria for 24-week total treatment. In ILLUMINATE there was no benefit in extending therapy to 48 weeks.
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In ILLUMINATE, 72% of people overall achieved SVR with telaprevir-based therapy. New data from this study showed that 60% of African Americans/Blacks and 63% of people with advanced liver fibrosis or cirrhosis achieved SVR with telaprevir-based therapy in the overall study analysis. Of African Americans/Blacks whose virus was undetectable at weeks 4 and 12, 88% of people achieved SVR in both the 24-week and 48-week randomized treatment arms. There was no control arm of pegylated-interferon and ribavirin alone in ILLUMINATE.

What about treating with telaprevir in combination with pegylated interferon/ribavirin in genotype 1 patients that "Have Treated before" and failed.
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Nov 2010 The REALIZE Trial was for people who "had been" treated before but did not achieve a viral cure

A fact sheet on the Phase 3 telaprevir development program is available at http://www.vrtx.com/aasld2010.html

Phase 3 REALIZE Trial

REALIZE was the second pivotal Phase 3 trial and was designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon-based therapy but did not achieve a cure. REALIZE is the only Phase 3 clinical trial to date of an investigational direct-acting antiviral to include all major subgroups of difficult-to-treat patients including null responders, who were defined as people who had a less than a 2 log10 reduction in viral load by week 12 of a prior course of therapy.
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October 2010
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Details of the trial looked at 662 hepatitis C patients whose bodies seemed to be resistant to all other treatments.

. The participants were divided in 3 groups
.The ones who responded to treatment but then relapsed during the follow-up period were put in the first group, patients who partially responded to treatment but whose virus never completely disappeared consisted the second group, while patients who never responded well to treatment at all were a part of the third group.
The total treatment period was extended to 48 weeks from the regular 24 weeks as these patients have a form of the hepatitis C virus that is more stubborn or harder to treat.;

Results of the trial
65 percent of patients treated with telaprevir plus the standard of care were cured, or sustained viral response compared to 17 percent of patients in the control group who were re-treated with just the standard of care, the trial claimed.

Dividing the results into the different groups, 86 percent of re-lapsers were cured after telaprevir treatment compared to 24 percent in the control arm.Among the second group, the cure rate for the telaprevir-treated patients was 57 percent compared to 15 percent for the control arm.

Finally, in the last group which consisted of the most difficult to treat patients, telaprevir achieved a 31 percent cure rate compared to 5 percent for the control arm.Results across all three patients types were statistically significant in favor of telaprevir over standard of care, officials report.
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What about treating with boceprevir in combination with pegylated interferon/ribavirin in genotype 1 patients who "Have Never" treated before ?

. (Never Treated Before)
Boceprevir SPRINT-2 trial
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Nov 2010 From CCO : SPRINT-2: Boceprevir Plus PegIFN/RBV for 24 Weeks Improves SVR Rates vs PegIFN/RBV in Treatment-Naive Patients With Genotype 1 HCV
*To See Data At CCO Free Registration Is Required
.Patients with genotype 1 hepatitis C virus have had meager treatment response rates compared with genotype 2 and 3 patients -- especially if they're African American. So to compare the safety and efficacy of the two strategies in this genotype, as well as outcomes for blacks with this subtype, the researchers enrolled 1,097 treatment-naive patients, 159 of whom were African American, in the SPRINT-2 trial. Patients were randomized to one of three groups: 48 weeks of interferon and ribavirin along with placebo, 48 weeks of the standard combination plus boceprevir, or 24 weeks of triple therapy.
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All three arms had a four-week lead-in phase with peginterferon and ribavirin alone. After that, the two drug groups received an additional 800 mg of boceprevir three times a day.The primary endpoint was sustained virologic response 24 weeks after therapy. The researchers found that both boceprevir groups had higher SVR rates at that point than the control group.
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In an intention-to-treat analysis among white patients, 67% of those in the short-course group achieved sustained viral response, as did 68% of the long-treatment-course group, compared with just 40% of controls (P less then 0.0001). Only 8% of those on full treatment and 9% of those on the short course relapsed, compared with 23% of those on placebo.
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Among black patients, 53% of those on the full treatment and 42% of those on the short course had sustained virologic response, compared with 23% of those on placebo (P=0.004 and P=0.044, respectively). With full treatment, 17% of blacks relapsed, along with 12% of those on the short course and 14% of those on placebo.
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The trial had a "stopping rule" mandating that patients discontinue treatment if they don't respond in the first 24 weeks. Among white patients, 27% of those on standard combination therapy discontinued compared with 8% of those on short therapy and 9% of those on the full course.
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For blacks, 46% of those on placebo discontinued treatment, compared with 17% of those on the short course and 15% of those on the full course of triple therapy.Treatment appeared to be associated with two side effects compared with placebo -- anemia and a distorted sense of taste, or disgeusia.
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Overall, patients on treatment had greater use of erythropoietin(rescue drugs) to treat anemia compared with controls (43% for short- and full-course, versus 24% of those on placebo). More boceprevir patients also had to reduce their treatment dose due to anemia (20% and 21% versus 13%).
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Other adverse events included nausea, headache, and fatigue, at similar rates across all three groups.
.This is a little easier to follow from HCV Advocate
Oct 2010


The SPRINT-2 study included 1,097 HCV genotype 1
treatment-naïve patients (never been treated). The treatment
protocol consisted of a 4 week lead-in phase of
PegIntron plus ribavirin (without boceprevir), followed
by the triple combination of boceprevir, PegIntron
and ribavirin. Duration and continuation of treatment
was guided by the type of on-treatment response to the
medications.*
.The SVR or sustained virological response rates (HCVRNA negative 24 weeks after the last dose of medicine is taken) by different treatment arms are listed below:
.a. If HCV RNA (viral load) negative at week 8 through week 24,
triple therapy was continued for a total treatment duration of 28 weeks;
sustained virological response (SVR) = 63%
a. If HCV RNA positive at week 8 but undetectable at week 24, boceprevir was stopped at week 28 and PegIntron/ribavirin combination therapy (without boceprevir) was continued for a total treatment duration of 48 weeks;SVR = 66%
a. The control arm was standard of care – PegIntron plus ribavirin—with a treatment duration of 48weeks;SVR = 38%
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African Americans/Blacks—Treatment Response
There were also 159 African American/Black patients in the study—
African Americans/Blacks comprised 15% of the patient population in this trial.
The SVR rates by different treatment arms are listed below:
.a. If HCV RNA negative at week 8 through week 24,triple therapy was continued for a total treatment duration of 28 weeks: SVR = 42%
a.If HCV RNA positive at week 8 but undetectable at week 24, boceprevir was stopped at week 28 andPegIntron/ribavirin combo therapy without boceprevir) was continued for a total treatment duration of 48weeks; SVR = 53%
a. The control arm was standard of care – PegIntron plus ribavirin—with a treatment duration of 48weeks; SVR = 23%
.*If any patients were HCV RNA positive at week 24 all treatment was stopped.
..What about treating with boceprevir in combination with pegylated interferon/ribavirin in genotype 1 patients who "Have Treated" before and failed ?

.Nov 2010 RESPOND-2 Trial

The final results of the RESPOND-2 trial demonstrated that combination therapy with Boceprevir yields higher sustained virologic response (SVR) rates for patients with hepatitis C virus (HCV) genotype 1 who did not respond to or relapsed after treatment with peginterferon and ribavirin.
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In treatment-failure patients in HCV RESPOND-2, boceprevir increased SVR rates to 59 percent for the RGT arm (95/162) and 66 percent for the 48-week treatment arm (107/161) compared to 21 percent for control (17/80).
.• Control arm received peginterferon alpha 2b and ribavirin for 48 weeks
• Second arm received 4 weeks of lead-in therapy of peginterferon alpha 2b and ribavirin followed by response-guided therapy of peginterferon alpha 2b and ribavirin combined with 800 mg of Boceprevir three times a day
• Third arm received 4 weeks of lead-in therapy of peginterferon alpha 2b and ribavirin followed by 44 weeks of peginterferon alpha 2b and ribavirin combined with 800 mg of Boceprevir
At 24 weeks after conclusion of treatment, the control arm achieved a SVR of 21 percent.
Adding Boceprevir to the treatment increased SVR to 59 percent for the second arm and 67 percent for the third arm.
It was noted that previous relapsers fared better than nonresponders in all arms. The therapy was well-tolerated, and the most common reason for discontinuing treatment was for patients who still had detectable HCV-RNA at week 12..

Again From HCV Advocate Fact Sheet
..HCV RESPOND 2
The RESPOND 2 study included 403 HCV genotype 1
“treatment-failure” patients. The study included a 4
week lead-in phase of PegIntron plus ribavirin
(without boceprevir), followed by the triple combination
of boceprevir, PegIntron and ribavirin1 and treatment
duration was based on type of on-treatment response.
.The SVR rates and duration of treatment periods for all
patients are listed below.
a. If HCV RNA negative at week 8 and at week 12 the total
treatment duration was 36 weeks; SVR = 59%
a. IF HCV RNA positive at week 8, but undetectable at
week 12, boceprevir was stopped at week 36 and the
combination of PegIntron/ribavirin was continued for a
total treatment duration of 48 weeks; SVR = 66%
a. Control arm was standard of care – combination of
PegIntron plus ribavirin—for a total treatment duration
of 48 weeks; SVR = 21%
*If any patients were HCV RNA positive at week 12 all
treatment was stopped.
.It is important to know that the treatment duration in the
boceprevir containing arms were 28, 36 or 48 weeks
depending on the type of on-treatment response.
Telaprevir

New *OPTIMIZE TRIAL/Telaprevir Genotype 1 For People "Who Have Not Treated Previously"

Patient screening for enrollment in OPTIMIZE study is expected to start in November 2010...




This information and more is avaliable at the following sites HCV Advocate ,CCO, Medpage, AASLD, Natap, HIV and Hepatitis, The Street.com. and TheMedGuru


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