Agent Boosts Plateletsin ITP and Thrombocytopenia-Associated HCV
NEW YORK, Nov. 28 -- Eltrombopag (Promacta), an investigative thrombopoietin-receptor agonist, has boosted platelets in both immune thrombocytopenic purpura and hepatitis C-related cirrhosis, according to early trials.Higher daily doses elevated platelet counts to at least 50,000 per mm3 within two weeks in more than 80% of patients with relapsed or refractory chronic immune (or idiopathic) thrombocytopenic purpura, reported James B. Bussel, M.D., of Weill Cornell Medical College here, and colleagues.
Action Points
Caution interested patients that the early results for this investigative agent reported in these studies need to be confirmed in larger, longer-term phase III studies.
Inform interested patients that there is no FDA-approved treatment for thrombocytopenia in HCV-infected patients, although several options are available for treating chronic immune thrombocytopenic purpura.
A significant increase in platelets was also seen in 74% to 95% of eltrombopag-treated HCV patients with cirrhosis-related thrombocytopenia, a major reason why patients cannot endure antiviral treatments, reported John G. McHutchison, M.D., of Duke in Durham, N.C., and colleagues.
Results of both trials were reported in the Nov. 29 issue of the New England Journal of Medicine. Robert S. Schwartz, M.D., an NEJM editor, cautioned in an accompanying editorial, "The results reported for thrombopoietin-receptor agonists are too preliminary for any definitive statement about applications in clinical practice."
However, for hematologists thwarted by failure of every treatment for patients with ITP, he said, "a new, safe way of treating the disease would be a considerable advance."
Dr. Bussel's group conducted a multicenter phase I trial comparing oral eltrombopag and placebo. Patients were randomized to once-daily placebo or 30, 50, or 75 mg of eltrombopag for six weeks or until platelet counts reached 200,000 per mm3.
The trial included 118 adults with chronic ITP and platelet counts below 30,000 per mm3 who had failed at least one standard treatment, typically glucocorticoids or IV immunoglobulins. Among them, 47% had undergone splenectomy and 32% were receiving concomitant medication for the disease.
The trial was stopped at the first interim analysis when the two highest dose groups met predefined stopping criteria for efficacy.
Most patients on the higher doses reached the primary endpoint, a platelet count of 50,000 or more per mm3 on day 43. This included 81% on the 75-mg dose and 70% on the 50-mg dose but only 28% on the 30-mg dose and 11% of controls (P0.001).
The same results were seen without the last-observation-carried-forward analysis (73%, 56%, 22%, and 10%, respectively, P=0.002 for 50 mg versus placebo and P=0.001 for 75 mg versus placebo).
Median platelet counts approached the normal 150,000 to 400,000 per mm3 range by day 15 in both of the higher dose eltrombopag groups but returned almost to baseline within two weeks of the last dose.
Platelet counts rose above 200,000 per mm3 during the study in 4% of placebo group patients compared with 14% of those on 30 mg, 37% on 50 mg, and 50% on 75 mg of eltrombopag.
Bleeding events decreased during treatment with the higher doses. Adverse events were similar in incidence and severity to those in the placebo group.
For HCV-related cirrhosis, Dr. McHutchison's multicenter phase II trial randomized 74 patients with platelet counts of 20,000 to less than 70,000 per mm3 (median 55,000) to the same three dosages or placebo once daily for four weeks.
Patients who reached a platelet count of 70,000 or 100,000 per mm3 by week four could start HCV treatment with peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron), respectively, plus ribavirin. Eltrombopag or placebo continued during the 12-week regimen.
This trial was also discontinued early when a predetermined criterion was met.
Platelet counts rose to 100,000 per mm3 or more at week four -- the primary endpoint -- with eltrombopag in a dose-dependent manner (P0.001 overall and versus placebo for each dose group).
Among the patients who could receive antiviral treatment were 22% of those on placebo, 71% on 30 mg of eltrombopag, 74% on 50 mg of eltrombopag, and 91% on 75 mg of the agent.
During the antiviral treatment phase, platelet counts were consistently higher with eltrombopag than with placebo. Despite a drop in platelet counts in all three eltrombopag groups during antiviral treatment, "perhaps owing to the antiplatelet effect of peginterferon," levels remained above the 50,000 per mm3 threshold at which a reduction in the peginterferon dose is recommended.
The most common side effects of eltrombopag were headache, dry mouth, abdominal pain, and nausea, but they did not cause treatment discontinuation.
Both research groups said their findings require confirmation in phase III trials with longer duration.
Primary source: New England Journal of MedicineSource reference: McHutchison JG, et al "Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C"N Engl J Med 2007; 357: 2227-36. Additional source: New England Journal of MedicineSource reference: Bussel JB, et al "Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura"N Engl J Med 2007; 357: 2237-47. Additional source: New England Journal of MedicineSource reference: Schwartz RS, "Immune thrombocytopenic purpura -- from agony to agonist"N Engl J Med 2007; 357: 2299-2301.
Showing posts with label HCV. Show all posts
Showing posts with label HCV. Show all posts
Thursday, November 29, 2007
Tuesday, November 13, 2007
AASLD: Protease Inhibitors Open New Front on HCV
SAN FRANCISCO, Nov. 14 - Protease inhibitors may soon do for the hepatitis C virus (HCV) what they've done for HIV -- namely, keep the virus in check.
Action Points
Inform interested patients that the drugs described here appear to be safe and effective against hepatitis C viral infections, but have not been approved for clinical use, and may be about three years away from FDA approval.
These studies were published as abstracts and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
That's according to European researchers who presented results of early studies of two new protease inhibitors for HCV at the annual meeting of the American Association for the Study of Liver Diseases here today.
In one study, an investigational oral agent called VX-950 was shown to have potent antiviral activity and to be well tolerated at all dose levels in a 14-day phase IB study, reported Henk Reesink, M.D., of the Academic Medical Center in Amsterdam, The Netherlands.
VX-950 is a highly selective inhibitor of HCV protease NS3-4A, an enzyme important in the viral replication cycle.
Dr. Reesink reported on the final results of the study, which involved 24 healthy volunteers and 36 patients with HCV genotype 1 infection, the form most resistant to conventional therapy with pegylated interferon (PEG-IFN) and ribavirin. Patients and healthy volunteers were divided into three dosing groups on two different schedules.
In the first part of the study, participants received either placebo or VX-950 at one of three dose levels: 450 mg, 750 mg, or 1,250 mg every eight hours for five days. In the second half, patients received VX-950 on the same schedule (except for twice daily instead of three-times daily dosing for those on the 1,250 mg dose) for 14 days.
The primary study endpoints were safety and tolerability, but there was also an efficacy component as a secondary endpoint
The investigators found that the drug was safe and well tolerated at all dose levels in both healthy volunteers and the HCV-positive participants, with no serious adverse events and no discontinuations of therapy because of intolerability. The most commonly reported drug-related adverse events were headache and diarrhea, which occurred equally in the active drug and placebo groups.
In terms of efficacy, every patient had at least a 2-log (100-fold) reduction in viral load, and in the 750 mg group, in which the highest trough plasma concentrations of the protease inhibitor were seen, there was a median reduction in HCV RNA of 4.4 log (over 10,000 fold) at the end of 14 days of dosing.
Among the other dosing groups, in which plasma trough concentrations were lower, there was also a potent antiviral effect, with HCV RNA reductions > 2 log (100-fold) occurring between days three and seven. From days seven to 14, however, investigators saw an increase in viral load, Dr. Reesink said.
In addition, median alanine aminotransferase (ALT) levels normalized during the two-week dosing period in all dose groups, with a median change from base line of 25-30 U/L.
Dr. Reesink noted that the drug produced a rapid viral response, with 26 of 28 patients receiving any dose of VX-950 having more than a 3-log (1000 fold) reduction in plasma HCV RNA within two days.
In the second study, Stephan Zeuzem, M.D., of Saarland University Hospital in Homburg/Saar, Germany and colleagues presented data on a different protease inhibitor, dubbed SCH503034, which has also been shown in preclinical studies (replicon assays) to have potent activity against HCV-1.
In a double-blind dose-escalation trial, the investigators looked at SCH503034 in adults with HCV-1 who had failed therapy with PEG-IFN. The definition of failure used in the study was a 2-log (100-fold) reduction in HCV RNA after 12 weeks.
Patients were randomized to either placebo or oral SCH 503034 in one of four doses: 100 mg b.i.d., 200 mg b.i.d., 400 mg b.i.d. or 400 mg t.i.d. for 14 days
In all, 45 patients received the active drug and 16 received placebo. The authors found that the protease inhibitor was rapidly absorbed following oral administration of capsules with a mean therapeutic effect at one to two hours across doses, as well as dose-related increases in peak concentrations.
The highest plasma trough concentrations occurred in the 400 mg thrice-daily group, Dr. Zeuzem noted. "SCH 503034 exhibited potent dose-related antiviral activity that was first detectable 24 hours post-dose," he said.
Mean viral load reductions correlated positively with exposure to the drug, with patients in the 400 mg t.i.d. dosing group having a mean reduction of 2.06 log10 from baseline (range 1.1 to 2.7 log).
As with VX-950, there was a significant decline in liver enzymes (AST and ALT) corresponding to viral load reductions. This agent also was well tolerated at all dose levels.
Asked whether resistance to protease inhibitors for HCV might be expected to become problematic as it is with similar agents for HIV, Dr. Reesink said that whereas protease inhibitors for HIV must be taken indefinitely, it's expected that patients with HCV will only need to take PIs for as long as it takes to ensure adequate viral suppression or clearance, which could be as little as one year.Primary source: AASLDSource reference: Zeuzem S et al Anti-viral Activity of SCH Monotherapy in Hepatitis Interferon (Peg-IFN). Abstract 94, presented Nov. 14. Additional source: AASLDSource reference: Reesink H W et al. Final Results of a Phase Ib Multiple-Dose Study of VX-950, A Hepatitis C Virus Protease Inhibitor. Abstract 96 presented Nov. 14.
SAN FRANCISCO, Nov. 14 - Protease inhibitors may soon do for the hepatitis C virus (HCV) what they've done for HIV -- namely, keep the virus in check.
Action Points
Inform interested patients that the drugs described here appear to be safe and effective against hepatitis C viral infections, but have not been approved for clinical use, and may be about three years away from FDA approval.
These studies were published as abstracts and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
That's according to European researchers who presented results of early studies of two new protease inhibitors for HCV at the annual meeting of the American Association for the Study of Liver Diseases here today.
In one study, an investigational oral agent called VX-950 was shown to have potent antiviral activity and to be well tolerated at all dose levels in a 14-day phase IB study, reported Henk Reesink, M.D., of the Academic Medical Center in Amsterdam, The Netherlands.
VX-950 is a highly selective inhibitor of HCV protease NS3-4A, an enzyme important in the viral replication cycle.
Dr. Reesink reported on the final results of the study, which involved 24 healthy volunteers and 36 patients with HCV genotype 1 infection, the form most resistant to conventional therapy with pegylated interferon (PEG-IFN) and ribavirin. Patients and healthy volunteers were divided into three dosing groups on two different schedules.
In the first part of the study, participants received either placebo or VX-950 at one of three dose levels: 450 mg, 750 mg, or 1,250 mg every eight hours for five days. In the second half, patients received VX-950 on the same schedule (except for twice daily instead of three-times daily dosing for those on the 1,250 mg dose) for 14 days.
The primary study endpoints were safety and tolerability, but there was also an efficacy component as a secondary endpoint
The investigators found that the drug was safe and well tolerated at all dose levels in both healthy volunteers and the HCV-positive participants, with no serious adverse events and no discontinuations of therapy because of intolerability. The most commonly reported drug-related adverse events were headache and diarrhea, which occurred equally in the active drug and placebo groups.
In terms of efficacy, every patient had at least a 2-log (100-fold) reduction in viral load, and in the 750 mg group, in which the highest trough plasma concentrations of the protease inhibitor were seen, there was a median reduction in HCV RNA of 4.4 log (over 10,000 fold) at the end of 14 days of dosing.
Among the other dosing groups, in which plasma trough concentrations were lower, there was also a potent antiviral effect, with HCV RNA reductions > 2 log (100-fold) occurring between days three and seven. From days seven to 14, however, investigators saw an increase in viral load, Dr. Reesink said.
In addition, median alanine aminotransferase (ALT) levels normalized during the two-week dosing period in all dose groups, with a median change from base line of 25-30 U/L.
Dr. Reesink noted that the drug produced a rapid viral response, with 26 of 28 patients receiving any dose of VX-950 having more than a 3-log (1000 fold) reduction in plasma HCV RNA within two days.
In the second study, Stephan Zeuzem, M.D., of Saarland University Hospital in Homburg/Saar, Germany and colleagues presented data on a different protease inhibitor, dubbed SCH503034, which has also been shown in preclinical studies (replicon assays) to have potent activity against HCV-1.
In a double-blind dose-escalation trial, the investigators looked at SCH503034 in adults with HCV-1 who had failed therapy with PEG-IFN. The definition of failure used in the study was a 2-log (100-fold) reduction in HCV RNA after 12 weeks.
Patients were randomized to either placebo or oral SCH 503034 in one of four doses: 100 mg b.i.d., 200 mg b.i.d., 400 mg b.i.d. or 400 mg t.i.d. for 14 days
In all, 45 patients received the active drug and 16 received placebo. The authors found that the protease inhibitor was rapidly absorbed following oral administration of capsules with a mean therapeutic effect at one to two hours across doses, as well as dose-related increases in peak concentrations.
The highest plasma trough concentrations occurred in the 400 mg thrice-daily group, Dr. Zeuzem noted. "SCH 503034 exhibited potent dose-related antiviral activity that was first detectable 24 hours post-dose," he said.
Mean viral load reductions correlated positively with exposure to the drug, with patients in the 400 mg t.i.d. dosing group having a mean reduction of 2.06 log10 from baseline (range 1.1 to 2.7 log).
As with VX-950, there was a significant decline in liver enzymes (AST and ALT) corresponding to viral load reductions. This agent also was well tolerated at all dose levels.
Asked whether resistance to protease inhibitors for HCV might be expected to become problematic as it is with similar agents for HIV, Dr. Reesink said that whereas protease inhibitors for HIV must be taken indefinitely, it's expected that patients with HCV will only need to take PIs for as long as it takes to ensure adequate viral suppression or clearance, which could be as little as one year.Primary source: AASLDSource reference: Zeuzem S et al Anti-viral Activity of SCH Monotherapy in Hepatitis Interferon (Peg-IFN). Abstract 94, presented Nov. 14. Additional source: AASLDSource reference: Reesink H W et al. Final Results of a Phase Ib Multiple-Dose Study of VX-950, A Hepatitis C Virus Protease Inhibitor. Abstract 96 presented Nov. 14.
Thursday, November 08, 2007
AASLD: Telaprevir Yields Good Response in Combo Therapy for HCV
BOSTON, Nov. 7 -- A regimen containing the investigational protease inhibitor telaprevir in combination with a pegylated interferon and ribavirin appears to produce sustained viral responses in two-thirds of patients with hepatitis C (HCV) infections, said U.S. and European investigators.
Action Points
Explain to patients that there are effective therapies for the treatment of hepatitis C infection, and encourage those who may be at risk to be tested.
Explain that telaprevir is an investigational agent and has not yet been approved by the FDA for treatment of HCV.
Note that this study was published as an abstract and presented at a conference. The data and conclusions should be considered to be preliminary until published in a peer-reviewed publication.
At 24 weeks, 61% of patients infected with HCV genotype 1 had a sustained viral response (SVR) in the PROVE1 (U.S.) trial, and 65% had an SVR in the European PROVE2 study.
Interim analyses of data from the ongoing phase IIb trials were reported at the American Association for the Study of Liver Diseases meeting here by Christophe Hezode, M.D., of the Hôpital Henri Mondor, in Creteil, France, for the PROVE2 investigators, and Ira M. Jacobson, M.D., of Weill Medical College of Cornell University, for the PROVE1 investigators.
In both of the PROVE studies, patients were randomized into one of four arms. In PROVE1, three groups received telaprevir 750 mg every 8 hours, pegylated interferon alpha 2a (Peg-IFN) 180 μg/week, plus ribavirin (Rebetol) 1,000 to 1,200 mg/day for 12 weeks.
One of the three groups received no additional therapy, one received 12 additional weeks of Peg-IFN and ribavirin, and one received 36 additional weeks. Controls received up to 48 weeks of Peg-IFN and ribavirin, with no telaprevir.
In PROVE2, patients received telaprevir-based regimens for 12, 24, or 48 weeks, compared with 48 weeks of Peg-IFN and ribavirin for controls. In one of the telaprevir arms, patients received the protease inhibitor plus Peg-IFN but no ribavirin for 12 weeks.
Baseline patient characteristics in PROVE1 were similar across telaprevir treatment and control arms. The median HCV RNA (by Roche Taqman assay) at entry was similar across all arms, and 87% of patients had a high viral load, defined as greater than 800,000 IU/mL. The mean patient age was 49 (range 21 to 63), and the mean weight was 82.1 kg (range 46 to 136).
The PROVE2 patient parameters at baseline were similar to those of the patients in the PROVE1 study.
Rates of SVR at 24 weeks among patients in the 12-week treatment arm with ribavirin were 35% in PROVE1 and 59% in PROVE2.
The SVR rate in the 12-week telaprevir plus Peg-IFN without ribavirin arm in PROVE2 was 29%.
Sustained viral response results from the control arms of PROVE1 and PROVE2 were not available, the presenters said, but noted that, at the time of the interim analysis, 45% of controls in PROVE1 had undetectable HCV RNA (10 IU/mL) at the end of treatment (48 weeks of standard Peg-IFN plus ribavirin).
In PROVE2, 59% of controls, who received the same regimen as controls in PROVE1, had undetectable HCV RNA at week 36 of treatment.
Dr. Jacobson said that among those patients who achieved a rapid virologic response and had data available for an SVR analysis, 91% had an SVR at 12 weeks.
Data from the combined studies showed that viral breakthrough occurred in 5% of patients who received telaprevir during the first 12 weeks of treatment. Most viral breakthroughs occurred in the first month of treatment, and were generally associated with low blood levels of interferon, Dr. Jacobson said.
The combined relapse rate for patients who completed 24 weeks of treatment was 9%. Among those patients who had a rapid virologic response and completed 24 weeks of therapy, viral relapse occurred in 7% during the post-treatment period.
The adverse events occurring significantly more frequently among telaprevir-treated patients compared with controls included gastrointestinal disorders, rash, pruritus, and anemia.
In the U.S., 18% of all patients on telaprevir for 12 weeks discontinued therapy, compared with 3% of controls. After week 12, discontinuations because of adverse events were 8% in both the telaprevir and control arms.
In PROVE2, the overall discontinuation rate through 12 weeks was 14% across all telaprevir treatment arms and 6% in the control arm.
"Combination therapy including, for example, telaprevir as a targeted protease inhibitor has the very high potential to increase sustained virologic response rate above current regimens by also decreasing the overall duration of therapy," Dr. Hezode said.
Following the presentation of the PROVE1 data, Dr. Jacobson was asked by Jay M. Hoofnagle, M.D, from the National Institute of Diabetes and Digestive and Kidney Disease, why the viral response rates were not higher among controls.
"It's a little bit discouraging that you only got a 65% end-of-treatment response [with telaprevir regimens]," Dr. Hoofnagle said. "Frankly, that's what you get with genotype 1 with most studies of Peg and ribavirin…You keep reporting data from this trial and the patients in the trial are still in the trial, so you've ruined the blind and the objectivity of the trial by continually reporting the data, and I think that's why you have such a bad result in the control group."
The PROVE1 and PROVE2 investigators plan to present results of another analysis of the trial in 2008.
The study was funded by Vertex, maker of telaprevir. Dr. Jacobson and Dr. Hezode have received grant and research support from the company.
Primary source: American Association for the Study of Liver DiseasesSource reference: Zeuzem S, et al "PROVE2: Phase II Study of VX950 (TELAPREVIR) in Combination with Peginterferon ALFA2A With or Without Ribavirin in Subjects With Chronic Hepatitis C, First Interim Analysis" AASLD Meeting 2007; Abstract 80 presented Nov. 5. Additional source: American Association for the Study of Liver DiseasesSource reference: Jacobson IM, et al "Interim Analysis Results from a Phase 2 Study of Telaprevir with Peginterferon alfa-2A and Ribavirin in Treatment naïve Subjects with Hepatitis C" AASLD Meeting 2007; Abstract 177 presented Nov. 6.
BOSTON, Nov. 7 -- A regimen containing the investigational protease inhibitor telaprevir in combination with a pegylated interferon and ribavirin appears to produce sustained viral responses in two-thirds of patients with hepatitis C (HCV) infections, said U.S. and European investigators.
Action Points
Explain to patients that there are effective therapies for the treatment of hepatitis C infection, and encourage those who may be at risk to be tested.
Explain that telaprevir is an investigational agent and has not yet been approved by the FDA for treatment of HCV.
Note that this study was published as an abstract and presented at a conference. The data and conclusions should be considered to be preliminary until published in a peer-reviewed publication.
At 24 weeks, 61% of patients infected with HCV genotype 1 had a sustained viral response (SVR) in the PROVE1 (U.S.) trial, and 65% had an SVR in the European PROVE2 study.
Interim analyses of data from the ongoing phase IIb trials were reported at the American Association for the Study of Liver Diseases meeting here by Christophe Hezode, M.D., of the Hôpital Henri Mondor, in Creteil, France, for the PROVE2 investigators, and Ira M. Jacobson, M.D., of Weill Medical College of Cornell University, for the PROVE1 investigators.
In both of the PROVE studies, patients were randomized into one of four arms. In PROVE1, three groups received telaprevir 750 mg every 8 hours, pegylated interferon alpha 2a (Peg-IFN) 180 μg/week, plus ribavirin (Rebetol) 1,000 to 1,200 mg/day for 12 weeks.
One of the three groups received no additional therapy, one received 12 additional weeks of Peg-IFN and ribavirin, and one received 36 additional weeks. Controls received up to 48 weeks of Peg-IFN and ribavirin, with no telaprevir.
In PROVE2, patients received telaprevir-based regimens for 12, 24, or 48 weeks, compared with 48 weeks of Peg-IFN and ribavirin for controls. In one of the telaprevir arms, patients received the protease inhibitor plus Peg-IFN but no ribavirin for 12 weeks.
Baseline patient characteristics in PROVE1 were similar across telaprevir treatment and control arms. The median HCV RNA (by Roche Taqman assay) at entry was similar across all arms, and 87% of patients had a high viral load, defined as greater than 800,000 IU/mL. The mean patient age was 49 (range 21 to 63), and the mean weight was 82.1 kg (range 46 to 136).
The PROVE2 patient parameters at baseline were similar to those of the patients in the PROVE1 study.
Rates of SVR at 24 weeks among patients in the 12-week treatment arm with ribavirin were 35% in PROVE1 and 59% in PROVE2.
The SVR rate in the 12-week telaprevir plus Peg-IFN without ribavirin arm in PROVE2 was 29%.
Sustained viral response results from the control arms of PROVE1 and PROVE2 were not available, the presenters said, but noted that, at the time of the interim analysis, 45% of controls in PROVE1 had undetectable HCV RNA (10 IU/mL) at the end of treatment (48 weeks of standard Peg-IFN plus ribavirin).
In PROVE2, 59% of controls, who received the same regimen as controls in PROVE1, had undetectable HCV RNA at week 36 of treatment.
Dr. Jacobson said that among those patients who achieved a rapid virologic response and had data available for an SVR analysis, 91% had an SVR at 12 weeks.
Data from the combined studies showed that viral breakthrough occurred in 5% of patients who received telaprevir during the first 12 weeks of treatment. Most viral breakthroughs occurred in the first month of treatment, and were generally associated with low blood levels of interferon, Dr. Jacobson said.
The combined relapse rate for patients who completed 24 weeks of treatment was 9%. Among those patients who had a rapid virologic response and completed 24 weeks of therapy, viral relapse occurred in 7% during the post-treatment period.
The adverse events occurring significantly more frequently among telaprevir-treated patients compared with controls included gastrointestinal disorders, rash, pruritus, and anemia.
In the U.S., 18% of all patients on telaprevir for 12 weeks discontinued therapy, compared with 3% of controls. After week 12, discontinuations because of adverse events were 8% in both the telaprevir and control arms.
In PROVE2, the overall discontinuation rate through 12 weeks was 14% across all telaprevir treatment arms and 6% in the control arm.
"Combination therapy including, for example, telaprevir as a targeted protease inhibitor has the very high potential to increase sustained virologic response rate above current regimens by also decreasing the overall duration of therapy," Dr. Hezode said.
Following the presentation of the PROVE1 data, Dr. Jacobson was asked by Jay M. Hoofnagle, M.D, from the National Institute of Diabetes and Digestive and Kidney Disease, why the viral response rates were not higher among controls.
"It's a little bit discouraging that you only got a 65% end-of-treatment response [with telaprevir regimens]," Dr. Hoofnagle said. "Frankly, that's what you get with genotype 1 with most studies of Peg and ribavirin…You keep reporting data from this trial and the patients in the trial are still in the trial, so you've ruined the blind and the objectivity of the trial by continually reporting the data, and I think that's why you have such a bad result in the control group."
The PROVE1 and PROVE2 investigators plan to present results of another analysis of the trial in 2008.
The study was funded by Vertex, maker of telaprevir. Dr. Jacobson and Dr. Hezode have received grant and research support from the company.
Primary source: American Association for the Study of Liver DiseasesSource reference: Zeuzem S, et al "PROVE2: Phase II Study of VX950 (TELAPREVIR) in Combination with Peginterferon ALFA2A With or Without Ribavirin in Subjects With Chronic Hepatitis C, First Interim Analysis" AASLD Meeting 2007; Abstract 80 presented Nov. 5. Additional source: American Association for the Study of Liver DiseasesSource reference: Jacobson IM, et al "Interim Analysis Results from a Phase 2 Study of Telaprevir with Peginterferon alfa-2A and Ribavirin in Treatment naïve Subjects with Hepatitis C" AASLD Meeting 2007; Abstract 177 presented Nov. 6.
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