AASLD 2009 News Updates November 9, 2009
- Changes in Growth Seen in Children on Peginterferon for Chronic HCV Infection
- AASLD: HCV Response Linked Strongly to Gene Variant
- Choice of Calcineurin Inhibitor Does Not Influence Outcome of Liver Transplantation in HCV-Positive Recipients: Presented at AASLD
- Vitamin D Has Benefits in Chronic HCV Infection
- AASLD: HCV Now an STD in New York
- What Is the Optimal Timing of Hepatitis C Antiviral Therapy before and after Liver Transplantation? Presented at AASLD
- SCYNEXIS` SCY-635 Demonstrates Positive Antiviral Activity in Combination with Approved and Investigational Anti-HCV Agents
- Idera Pharmaceuticals Presents Preclinical Data on IMO-2125, its Lead Drug Candidate for Chronic Hepatitis C Virus Infection, at Liver Meeting 2009
- AASLD: Survival Lower in HCV-Infected Women after Liver Transplant
- Canadian Programs Underscore Evidence of PEGETRON's Positive Outcomes in Treating HCV Infection
- Idenix Pharmaceuticals Presents Data on IDX184 for the Treatment of Hepatitis C Virus (HCV)
- Valeant Pharmaceuticals Highlights Taribavirin Phase IIb End of Study Data Presentation at American Association for the Study of Liver Disease (AASLD) Annual Meeting
- Viral Load Predicts Outcome of Liver Transplant Recipients with Hepatitis C: Presented at AASLD
- Schering-Plough Reports Potent Antiviral Activity with Narlaprevir (SCH 900518), an Investigational, Once-Daily Protease Inhibitor for Hepatitis C
- Extended HCV Treatment after Liver Transplant Has Benefits
- Ocera Therapeutics Presents Clinical Data Demonstrating AST-120 Relieves Pruritus in Patients with Liver Cirrhosis at the 60th Annual AASLD Meeting
- Twice Daily Oral Medication Shows Promise in Treating Patients with Hepatitis C
- Noninvasive Breath Test Predicts Survival in Patients with Viral Hepatitis
- BMY and ZGen present Phase 1B results for PEG-Interferon lambda in HCV patients
- Avila Presents Data on Its Novel, Orally-Available Protease Inhibitor, AVL-181, Demonstrating Viral Clearance of Hepatitis C Virus in Preclinical Models
- GlobeImmune's Hepatitis C Therapeutic Vaccine Combined with Standard of Care Increases End of Treatment Response Rate by 15%
- Pharmasset to Webcast an Investor Event from the AASLD Meeting
- African Americans Fare Worse After Undergoing Liver Transplantation Due to Hepatitis C
- Schering hep C drug promising in Phase II study
- Post-transplant Prophylactic Antiviral Treatment Does Not Prevent Recurrent Hepatitis C: Presented at AASLD
- More Than 80 Percent of HCV Genotype 1 Treatment-Naive Patients Achieved Sustained Virologic Response With Twice-Daily Telaprevir-Based Regimen
Changes in Growth Seen in Children on
Peginterferon for Chronic HCV Infection
Megan Brooks
Principle investigator Maureen M. Jonas, MD, from the
division of gastroenterology, hepatology, and nutrition at Children's Hospital,
"We've seen for a while that patients on this therapy
lose weight, but what is the significance of that?" Dr. Jonas said in an
interview with Medscape Gastroenterology.
To investigate, Dr. Jonas and colleagues studied 111
children with chronic hepatitis C who were treated with peginterferon alfa-2
(180 μg/1.73 m2 weekly) with or without ribavirin (15 mg/kg/day) for 24
weeks (nonresponders) or 48 weeks. The children ranged in age from
The investigators analyzed changes in weight, height, and
body mass index (
"The children lost a significant amount of weight on
therapy," Dr. Jonas told Medscape Gastroenterology. "They slowed
their growth, their
More specifically, at baseline, mean weight, height, and
Dual-energy X-ray absorptiometry analysis showed that
percentage body fat declined by 0.48% after 24 weeks on peginterferon (P = .06)
and 0.93% after 48 weeks (P = .006).
"Off therapy, the weight started to come back and sort
of recovered, the
"We have later data points
off-treatment, so we will be able to see if height does recover, only more
slowly because it is height, or if it doesn't recover, which could have
long-term ramifications in adolescents," Dr. Jonas said.
Estella Alonso, MD, from
Dr. Jonas has disclosed that she has consulted for
The Liver Meeting
2009: American Association for the Study of Liver Diseases 60th Annual Meeting:
Abstract 708. Presented
AASLD: HCV Response Linked Strongly to Gene Variant
By John Gever, Senior Editor, MedPage Today
Reviewed by Dori F. Zaleznik, MD; Associate Clinical
Professor of Medicine,
Dorothy Caputo, MA, RN, BC-
Action Points
●
Explain to
interested patients that HCV infection is currently treated with interferon and
ribavirin, and that this study shows that a certain genetic variant is
correlated with the likelihood of good responses to the drugs.
●
Explain
that a test for this genetic variant is not currently available. Also explain
that there is not an established alternative treatment available for patients
identified in such testing as less likely to have a good treatment response.
●
Note that
this study was published as an abstract and presented at a conference. These
data and conclusions should be considered preliminary until published in a
peer-reviewed journal.
Not only is the so-called CC variant of the IL28B gene
associated with long-term responses to treatment with pegylated interferon
(Pegasys, PEGIntron) and ribavirin (Rebetol), but it also predicts the speed of
response, said Alexander J. Thompson, MD, of
Thompson was part of a group that, in August, reported online in Nature that the CC genotype of IL28B, which encodes the lambda-3 form of interferon, is associated with sustained suppression of HCV. (See Gene Variant Predicts HCV Treatment Success)
Speaking here at the American Association for the Study of Liver Diseases meeting, Thompson reported on further analyses of the group's data, focusing on virologic responses after four and 12 weeks, referred to as rapid and early responses, respectively.
Thompson also provided additional insights into the effects on sustained responses, which were assessed 24 weeks after a 48-week treatment period with interferon and ribavirin.
As in the Nature report, the analysis used data on more than 1,600 participants in a clinical trial called IDEAL which compared the 2a and 2b forms of pegylated interferon in patients infected with HCV genotype 1. Genome-wide association studies were performed on tissue samples from these individuals, correlating their virologic responses to a large number of gene polymorphisms.
As Thompson reported here, sustained virologic response rates in patients with the CC genotype of IL28B were 69% in Caucasians, 48% in African-Americans, and 56% in Hispanics. For each group, these response rates were substantially higher than for two other genotypes, TC and TT.
Those ranged from 27% to 33% in whites, 13% to 15% in blacks, and 27% to 38% in Hispanics.
Overall, the adjusted odds ratio for sustained virologic response associated with CC versus the other genotypes was 5.2 (95% CI 4.1 to 6.7), the largest odds ratio of any pretreatment predictor.
Other baseline factors predicting sustained response rates included viral loads, white or Hispanic versus black ethnicity, baseline liver fibrosis, and fasting blood sugar.
Thompson said the IL28B genotype explained about half the difference in sustained response rates between Caucasians and African-Americans -- a difference that had been observed previously and which had never been adequately explained.
He reported that CC-genotype patients also responded more quickly to treatment in each ethnic group, compared with the TC and TT genotypes. At treatment week two, whites with the CC variant already showed log10 reductions in viral loads of 2.5, whereas white patients with the other genotypes had not yet achieved one-log reductions.
Differences were also apparent at weeks four and 12, Thompson said. However, the rate of decline in viral loads was about the same for all genotypes after week four.
The same pattern was seen in African-Americans and Hispanics, he said.
Another new finding was that the CC genotype predicted sustained responses in white patients who had not shown viral clearance by week four.
Those patients were 86% of the sample. More than half had the TC genotype and another 13% had the TT variant. In contrast, those who did achieve rapid virologic responses were predominantly the CC genotype (77%).
Nevertheless, in those not achieving rapid responses, 66% of those with the CC variant eventually obtained a sustained response, compared with 31% of TC and 24% of TT genotypes (P<0.0001), Thompson said.
Other researchers said the findings, when validated, would likely be practice-changing.
Scott Friedman, MD, president of AASLD and a hepatologist at
Mount Sinai School of Medicine in
Schering-Plough, which sells pegylated interferon-alfa-2b (PEGIntron), owns commercial rights to develop the genotype test.
A spokesman said the company was evaluating how best to bring it to market. He said Schering-Plough, which has little experience in developing or marketing diagnostic tests, was primarily interested in making it available as soon as possible.
He said the company had discussed nonexclusive licensing arrangements with other firms with the relevant capabilities, but no decisions had been made.
Friedman pointed out that, although genotype testing looked to be extremely useful in the short term, whether it would remain so when direct antiviral drugs for HCV become available -- expected in the next several years -- was unclear.
Thompson agreed that the IL28B polymorphism's effect on treatment response would have to be reevaluated for regimens including direct antivirals.
Other research needs include studies of the polymorphism in patients with nongenotype 1 HCV and whether it predicts responses to personalized duration of therapy.
In his presentation here, Thompson offered no new insights into the mechanism underlying the IL28B polymorphism's effects on treatment responses, beyond what the Nature paper had suggested -- namely, that interferon-lambda-3 helps mediate innate control of HCV.
This form of interferon appears to have its own unique receptor, but the downstream signalling path is believed to converge with that of interferon-alfa, the researchers said.
The IDEAL study was funded by Schering-Plough.
Thompson reported no potential conflicts of interest other
than the research funding. Several co-authors were employees of
Schering-Plough. Others reported relationships with a large number of other
firms including Roche,
Friedman reported relationships with Exalenz, sanofi-aventis, Axcan, Angion, Intercept, 7TM, Stromedix, and Celera.
Primary source: American Association for the Study of Liver Diseases
Source reference: Thompson
A, et al "Genome wide analysis of patients from the IDEAL study identifies
a polymorphism upstream of the Il28B (=IFNλ-3) gene that is strongly
associated with
Choice of Calcineurin Inhibitor Does Not Influence Outcome of Liver Transplantation in HCV-Positive Recipients: Presented at AASLD
By Cheryl Lathrop
Victoria Aguilera, Hepatogastroenterology Service, Hospital
Universitario La Fe,
In one-third of liver transplants, recurrent hepatitis C is aggressive. Immunosuppression influences the natural history of this infection. In HCV-infected transplant recipients, an association exists between the state of the patient's immunosuppression and the outcome after transplantation. However, data are conflicted in regard to the potential effect of calcineurin inhibitors on the outcome.
This study aimed to determine whether the choice of
calcineurin inhibitor makes a difference in survival and histologic outcome
after transplantation. Results from 310 patients who
underwent liver transplantation between 2001 and 2007 and were given tacrolimus
(
The primary endpoint was progression to severe disease, ie, bridging fibrosis, cirrhosis, cholestatic hepatitis, or death due to recurrent hepatitis C, within the first 2 years. Secondary endpoints were progression to fibrosis >1 determined by the first-year liver biopsy, the percentage of patients developing cholestatic hepatitis, no fibrosis in the first-year liver biopsy, and graft/patient survival. Liver biopsies were performed at 1- or 2-year intervals, and the antiviral treatment was chosen based on the results of the first-year biopsy.
The histologic outcome was similar for both groups: 29% of
Based on the results, the researchers concluded that post-transplantation outcome was not related to the choice of calcineurin inhibitor used.
[Presentation title:
Calcineurin Inhibitors and Outcome of Liver Transplantation in HCV-Positive
Recipients: Final Results of a Prospective Randomized Study. Abstract 511]
Vitamin D Has Benefits in Chronic HCV Infection
Megan Brooks
November 5, 2009 (Boston, Massachusetts) — Supplementing pegylated interferon-alfa2b and ribavirin with a daily dose of vitamin D might increase virologic response rates, according to results of a late-breaking abstract reported here at The Liver Meeting 2009, the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
"Vitamin D is a potent immunomodulator whose impact on
virologic response rates of interferon-based treatment of chronic HCV
[hepatitis C] is unknown," lead investigator Saif M. Abu-Mouch, MD, from
the Department of Hepatology,
"This preliminary study confirms the benefit of adding vitamin D to conventional antiviral therapy in patients with chronic HCV," Dr. Abu-Mouch told meeting attendees.
In the study, 58 patients with confirmed chronic HCV (genotype 1) were randomly assigned to peginterferon-alfa2b (1.5 µg/kg once weekly) plus ribavirin (1000 to 2000 mg/day). Thirty-one patients also received vitamin D (1000 to 4000 IU/day; serum level >32 ng/mL).
The vitamin D group had a higher mean body mass index (27 vs 24 kg/m2; P < .01), viral load (68% vs 58%; P < .01), and fibrosis (Metavir scores > F2, 55% vs 18%; P < .001) than the group that did not receive vitamin D. Demographics, disease characteristics, ethnicity, baseline biochemical parameters, and adherence to treatment were similar in the 2 study groups.
A rapid virologic response was seen at week 4 in 44% of the vitamin D group and in 18% of the control group. At week 12, Dr. Abu-Mouch told Medscape Gastroenterology, 96% of the vitamin D group (26 of 27 patients) were HCV RNA-negative, as assessed by reverse-transcriptase polymerase chain reaction, as was 48% of the control group (15 of 31 patients), which was a significant difference (P < .001), he said.
The combination of peginterferon and ribavirin, the standard of care for chronic HCV, achieves a sustained virologic response in 40% to 50% of naïve patients with genotype 1, the investigators explain in a meeting abstract. Vitamin D in combination with peginterferon-ribavirin "may have synergistic effects," Dr. Abu-Mouch said.
Meeting attendee
"It's also interesting," he said, "that the group treated with vitamin D had more severe disease than the control group. I think this can be considered a strong result from a small study.
The study did not receive commercial support. Dr. Abu-Mouch and Dr. Tsakiris have disclosed no relevant financial relationships.
The Liver Meeting
2009: 60th Annual Meeting of the American Association for the Study of Liver
Diseases (AASLD): Abstract LB20. Presented
What Is the Optimal Timing of Hepatitis C Antiviral Therapy before and after Liver Transplantation? Presented at AASLD
By Cheryl Lathrop
This strategy yields the greatest survival benefit with the
lowest associated cost; it reverses cirrhosis, and prevents decompensation,
transplantation, hepatocellular carcinoma (
Antiviral therapy for the treatment of HCV infection is used
both before and after liver transplantation. The objective of this study was to
determine the ideal timing for
The 4 treatment groups were as follows: (1) no antiviral treatment, (2) antiviral therapy in patients with compensated cirrhosis, (3) antiviral therapy in patients with decompensated cirrhosis, and (4) antiviral therapy in patients with recurrent HCV post transplant. A Markov model was constructed comparing treatment strategies. Outcomes of interest were total cost per patient, number of quality-adjusted life-years (QALYs) saved, number of deaths, number of HCCs, and number of transplants required. Each of the 4 treatment arms comprised 1,000 patients.
The total cost per patient for treatment during compensated cirrhosis was $331,425; the total cost per patient for each of the other 3 treatment groups was approximately $152,000 more. The life expectancy for treatment during compensated cirrhosis was almost 10 QALY; for the other 3 groups it was about 7 QALY.
In the 10-year outcome data, a total of approximately 250 patients died in the compensated cirrhosis treatment group; approximately 500 patients died in each of the other 3 groups. A total of approximately 175 patients had a transplant in the compensated cirrhosis treatment group; approximately 200 patients had a transplant in each of the other 3 groups. About 50 patients had regression of cirrhosis in the compensated-cirrhosis treatment group.
Treatment of patients with compensated cirrhosis was the most cost-effective strategy; it resulted in improved survival and decreased cost when compared with the other 3 strategies. Treatment after development of decompensated cirrhosis or post transplant was also cost-effective, but these patients derived less survival benefit at greater cost (when compared with patients treated during compensated cirrhosis). Patients who were allowed to develop more advanced disease had a considerably worse prognosis. All 3 treatment strategies appeared more cost-effective than "no treatment," which suggests that these patients may benefit from antiviral treatment.
"Given these results, we strongly recommend expeditious administration of antiviral therapy to patients with compensated cirrhosis before their disease advances," the authors stated.
These treatment strategies must be studied further, however, before they can be universally recommended, they advised.
[Presentation title:
Timing of Hepatitis C Antiviral Therapy Pre and Post Liver Transplantation: A
Decision Analysis Model. Abstract 503]
SCYNEXIS` SCY -635
Demonstrates Positive Antiviral Activity in Combination with Approved and
Investigational Anti-HCV Agents
--In VitroResults
presented in a poster session at AASLD; Phase 2 combination studies to be
initiated in 2Q 2010--
Dr. Yves Ribeill, President and Chief Executive Officer of
SCYNEXIS, said: "
According to the study,
"There is a significant need for more effective
treatments for HCV that work for a broader patient population and help overcome
resistance issues," said Sam Hopkins, Chief Scientific Officer of
SCYNEXIS. "
In a prior Phase 1b 15-day monotherapy study,
About
About SCYNEXIS
SCYNEXIS is a premier drug discovery and development
company delivering effective and innovative drug pipeline solutions to
pharmaceutical and global health partners. The Company, which is located in
Idera Pharmaceuticals
Presents Preclinical Data on IMO -2125, its
Lead Drug Candidate for Chronic Hepatitis C Virus Infection, at Liver Meeting
2009
-
CAMBRIDGE, Mass.--(BUSINESS
“Induction of endogenous interferon-alpha and other antiviral
proteins by
“One of our presentations today provides insights into the
mechanism of immune activation by
Abstract 1593: “
In this study,
Abstract 1597: “Gene
expression profiles induced by
In this study, the mechanism of immune activation by
The above
presentations are being made by Idera scientists today at
About
About
Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat
infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory
diseases, and for use as vaccine adjuvants. Our proprietary drug candidates are
designed to modulate specific Toll-like Receptors (TLRs), which are a family of
immune system receptors that direct immune system responses. Our pioneering
AASLD: Survival Lower in HCV-Infected Women after Liver Transplant
By John Gever, Senior Editor, MedPage Today
Reviewed by Dori F. Zaleznik, MD; Associate Clinical
Professor of Medicine,
Dorothy Caputo, MA, RN, BC-
BOSTON -- Women undergoing liver transplant as a result of hepatitis C virus (HCV) infection show poorer long-term survival rates and more frequent failure of the donor liver, compared with male recipients, a researcher said here.
Female gender was associated with a hazard ratio for five-year mortality of 1.46 (95% CI 1.04 to 2.03) in multivariate analysis of 195 female and 655 male liver recipients, reported Jennifer Lai, MD, of the University of California San Francisco.
Women were also at almost 40% higher risk for overall graft loss (HR 1.39, 95% CI 1.39 to 1.89), Lai said here at the annual meeting of the American Association for the Study of Liver Disease.
Action Points
· Explain to interested patients that the study suggested that HCV-infected women may have worse outcomes than men after liver transplantation, but the reasons were unknown.
· Explain that there are few alternatives to transplantation for patients with advanced liver disease related to HCV infection.
· Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
"Further studies are needed to evaluate modifiable donor factors and post-transplant therapies that influence [women's] outcomes," she told attendees at a plenary presentation.
She said previous studies were equivocal on whether gender affects survival and graft loss rates in HCV-infected liver transplant recipients.
Moreover, the earlier research included patients whose transplants occurred before the current system for allocating donor livers, based on Model for End-Stage Liver Disease (MELD) scores, was instituted earlier in the decade.
The study conducted by Lai and her colleagues included all adult liver transplant recipients with HCV-related liver disease at a network of four major centers from March 2002 to December 2007.
A co-diagnosis of hepatocellular carcinoma was not an exclusion, but patients with HIV or who were negative for HCV RNA after transplant were excluded, as were those whose grafts failed within a month of transplant.
Overall, with median follow-up of 3.1 years, 22% of transplant recipients had died and 25% had sustained graft loss.
Graft loss with recurrent HCV infection occurred in 10% of patients. Advanced recurrent disease was seen in 26%.
Lai said that women were at substantially increased risk for these latter outcomes -- a 44% increased chance of advanced recurrent HCV and 84% higher rates of graft loss associated with recurrent infection.
In addition to female gender, factors significantly associated with outcomes included:
· African-American race: HR for mortality 1.66 (95% CI 1.09 to 2.55); HR for graft loss 1.51 (95% CI 1.00 to 2.26)
· Post-transplant antiviral treatment: HR for mortality 0.57 (95% CI 0.40 to 0.80); HR for graft loss 0.70 (95% CI 0.51 to 0.95)
· Donor age, per year: HR for mortality 1.03 (95% CI 1.02 to 1.04); HR for graft loss 1.02 (95% CI 1.01 to 1.03)
Lai emphasized that these factors were adjusted for in the hazard ratios calculated for female gender.
She suggested several potential explanations for the higher risks that women appeared to run:
· Differential effects of aging in women compared with men
· Gender mismatch between donors and recipients -- these were more common with female versus male recipients in the study
· Renal impairment prior to transplant, also more likely to occur with women than men in the sample
Gregory Everson, MD, a hepatologist at the
He said one of the first studies to examine the role of gender in liver transplant outcomes had also found a disadvantage for women. "This kind of confirms the finding," Everson said.
He added that, at this point, there wasn't a clear clinical implication. Everson agreed with Lai that more research is needed to identify the factors underlying the gender differences and how they might be alleviated either prior to or after transplantation.
The study was supported by the National Institutes of Health.
Lai had no potential conflicts of interest. Other co-authors
reported relationships with Salix,
Everson reported relationships with Schering-Plough and Ortho Biotech.
Primary source: Hepatology
Lai J, et al "Hepatitis C virus (HCV) infected females are at higher risk of graft loss after liver transplantation (LT): A multicenter cohort study" Hepatology 2009; 50: S304A-305A.
Canadian Programs Underscore Evidence of PEGETRON's Positive Outcomes in Treating HCV Infection
- Canadian POWeR and REDIPEN(R) Programs
presented at the American Association for the Study of Liver Diseases Annual
Meeting -
Results from two significant Canadian studies underscore the growing
scientific evidence of PEGETRON's positive outcomes in the treatment of chronic
hepatitis C virus (HCV) infection. Canadian investigators across the country
collaborated to generate and analyze clinical data from the Canadian PEGETRON
POWeR (Prospective Optimal Weight-based Dosing Response) and REDIPEN programs,
which were presented at the American Association for the Study of Liver
Diseases (AASLD) Annual Meeting in
The first abstract, Determinants of Virologic Relapse Following Hepatitis C
antiviral Therapy: Analysis of the Canadian POWeR Program reports Genotype 1
(G1)-infected patients treated with peginterferon alfa-2b plus weight-based
ribavirin (PEGETRON) across 138 Canadian centres, achieved a sustained
virologic response (
In the second abstract, Outcomes of a Large, Inclusive Population-Based
Hepatitis C Treatment Program are similar to Randomized Controlled Trials:
Interim Results of the Canadian REDIPEN Program, a heterogeneous, but
representative, population of Canadian G1 patients treated with peginterferon
alfa 2b plus weight-based ribavirin (PEGETRON) achieved results similar to
those treated in randomized, controlled clinical trials. The G1
"The results from both the Canadian POWeR and REDIPEN programs support
previous findings from randomized controlled trials of PEGETRON," said Dr.
Curtis Cooper, M.D., Associate Professor of Medicine at the
These results reinforce the notion that outcomes achieved with PEGETRON across a large number of clinical trials are consistent and could be generalized to real-life clinical practice.
Source:
Idenix Pharmaceuticals
Presents Data on IDX 184 for the Treatment of
Hepatitis C Virus (HCV)
Data
from a three-day, phase I proof-of-concept study evaluating
the safety and antiviral activity of
"With favorable safety data and good antiviral activity for
Valeant Pharmaceuticals Highlights Taribavirin Phase IIb End of Study Data Presentation at American Association for the Study of Liver Disease (AASLD) Annual Meeting
ALISO VIEJO,
The results were presented in an abstract entitled
"Sustained Virologic Response Results for Weight-Based Taribavirin Versus
Weight-Based Ribavirin, in Naïve Chronic Hepatitis C, Genotype 1
Patients", with an oral presentation given by Fred Poordad, M.D., Chief of
Hepatology at the Center for Liver Disease and Transplant,
"The final results of this Phase IIb study are promising, and imply that comparable efficacy can be achieved when compared to ribavirin," said Dr. Poordad. "As is known for ribavirin, low doses are associated with a high relapse rate and, except for the lowest dose with taribavirin, relapse rates are also comparable to ribavirin. The safety of this ribavirin analog is of particular relevance in that its use is associated with significantly less anemia in an evolving era of small molecule therapies, where anemia appears to be more problematic."
The company has previously reported results from this Phase IIb trial exploring weight- based dosing of taribavirin at 20, 25 and 30mg/kg vs. weight-base dosed ribavirin 800-1400mg. The study consisted of 48 weeks of treatment with a 24-week post-treatment follow-up period. Consistent with previous reports, the viral response data continued to show comparable reductions in viral load for weight-based doses of taribavirin and ribavirin in a difficult-to-treat population of subjects infected with hepatitis C genotype 1 and end-of-study sustained virologic response rates were again comparable across the treatment groups. Relapse rates were identical for taribavirin 25mg/kg and weight-based doses of ribavirin. Importantly, the statistically significantly lower anemia rate for patients receiving taribavirin in the 20mg/kg and 25mg/kg arms versus the ribavirin control arm has been maintained at a rate similar to the end-of- treatment (week 48) throughout.
The most common adverse events during treatment were fatigue, nausea, flu-like symptoms, diarrhea, and insomnia. The incidence rates for these adverse events among treatment arms were generally comparable except with respect to diarrhea, where incidence of diarrhea was approximately twice as common in patients receiving taribavirin compared to patients receiving ribavirin. However, the diarrhea was generally mild and not treatment limiting for taribavirin or ribavirin patients.
The Phase IIb trial was a U.S. multi-center, randomized, parallel, open-label study in 278 treatment-naive, genotype 1 patients evaluating taribavirin at weight-based doses of 20 mg/kg, 25 mg/kg, and 30 mg/kg per day in combination with pegylated interferon alfa-2b. The control group was administered weight-based dose ribavirin (800/1000/1200/1400mg daily) and pegylated interferon alfa-2b. Overall treatment duration was 48 weeks with a post-treatment follow-up period of 24 weeks.
About Taribavirin
Taribavirin is an investigational compound that has not been
found by the Food and Drug Administration (FDA) or any other regulatory agency
to be safe or effective in the diagnosis, mitigation, treatment or cure of any
disease or illness. It may not be sold
or promoted in the
About Study 204
In the Phase IIb study (previously disclosed as Study 204),
278 treatment naïve, genotype 1 patients were randomized with the following
patient demographics: mean age 48.8 yr, 61.1% male, 30% African-American or
Latino, 80.7% viral load >=400,000 IU/mL and 82.1 kg mean weight. Week 72 efficacy and safety results for the
intention-to-treat (
About Valeant
Valeant Pharmaceuticals International (NYSE: VRX) is a multinational specialty pharmaceutical company that develops, manufactures and markets a broad range of pharmaceutical products primarily in the areas of neurology and dermatology. More information about Valeant can be found at www.valeant.com.
Viral Load Predicts Outcome of Liver Transplant Recipients with Hepatitis C: Presented at AASLD
By Cheryl Lathrop
BOSTON -- November 2, 2009 -- Viral load is an important factor and can predict the outcome of patients with hepatitis C virus (HCV) after liver transplantation, for both the development of the different types of recurrent HCV and patient survival, researchers stated here at the Liver Meeting 2009, the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
Ivo Graziadei, Department of Internal Medicine II, Medical
University of Innsbruck,
After liver transplant, recurrent HCV infection is ubiquitous and leads to graft loss and re-transplantation for 10% to 20% of liver transplant recipients. Donor, recipient, and viral parameters are the risk factors associated with HCV recurrence.
As there has been conflicting data reported about the viral load and the severity of recurrent HCV disease, the aim of this study was to analyse the impact of the viral load upon the severity of the recurrent HCV infection.
The study included data from 129 patients who received liver transplants due to HCV cirrhosis between 1980 and 2006 at the Medical University of Innsbruck and, who survived more than 6 months, and had histologically proven recurrent HCV infection.
Viral load was measured at week 2, and at months 3, 6, and 12 post-transplant (using the bDNA HCV RNA 3.0 assay by Bayer Diagnostics). There was a mean overall follow-up of 6.1 +- 3.6 years. Annual liver biopsies began in 2000; before that, biopsies were performed only in patients with elevated serum transaminases.
The majority of patients (81.4%) had no, or only mild to moderate HCV recurrence; 18.6% developed either a cholestatic type of recurrence (8.6%) or a rapid progression to advanced fibrosis/cirrhosis (9.1%).
Early viraemia (HCV RNA levels >6.0 log10 IU/mL) at week 2 were highly predictive for the cholestatic type of recurrence and poor patient survival. High viral loads (>6.5 log10 IU/mL) at month 3 were associated with recurrent cirrhosis of the liver allograft.
Presentation Title:
Viral Load Predicts Outcome of Hepatitis C Patients After Liver
Transplantation. Abstract 516
Schering-Plough Reports
Potent Antiviral Activity with Narlaprevir (SCH
900518), an Investigational, Once-Daily Protease Inhibitor for Hepatitis C
Interim results of
Phase IIa
BOSTON, Nov. 2 /PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE:
"These interim results, while preliminary, are very encouraging, and
showed that narlaprevir has potent antiviral activity in hepatitis C,"
said John Vierling, M.D., professor of medicine and surgery, chief of
hepatology, Baylor College of Medicine,
Importantly, patients in the lead-in narlaprevir arms also achieved improved rates of early virologic response (EVR), defined as undetectable virus at week 12 of treatment, with 85-87 percent of patients having undetectable virus at week 12 of narlaprevir treatment compared to 17 percent of patients at week 12 in the control arm.
Narlaprevir is a next-generation oral HCV protease inhibitor that achieves
once-daily dosing through the use of low-dose ritonavir as a metabolic
inhibitor. The
In this study, the rate of adverse events in the narlaprevir arms was similar to that in the peginterferon and ribavirin control arm, except for an increase in anemia (there were no discontinuations due to anemia) and an increase in low neutrophil counts (with no clinical sequelae). The most frequently seen adverse events up through 12 weeks of treatment were fatigue, nausea, flu-like illness, headache and insomnia. No increase in skin adverse events (rash or pruritus) beyond what was seen in the peginterferon and ribavirin control was observed.
For more information about ongoing narlaprevir clinical studies, please visit www.clinicaltrials.gov.
Extended
HCV Treatment after Liver Transplant Has Benefits
Megan Brooks
"In patients responding slowly to antiviral therapy following
orthotopic liver transplant, the 'stop rules' at weeks 12 and 24 should be
reconsidered," lead investigator Kimberly Brown, MD, head of the Division
of Gastroenterology at the
In an interview with Medscape Gastroenterology just prior to her presentation, Dr. Brown said: "There are some data in the pretransplant population that, if you extend antiviral therapy, you reduce relapse rates, especially in patients who are responding slowly. The purpose of our study was to extend therapy to see if we could do that in a posttransplant population, and the results suggest that we could."
The study involved 241 consecutive patients who underwent orthotopic liver transplant from 1999 to 2006 for HCV. Patients were offered therapy if they tested positive for HCV RNA, had recurrent HCV with at least stage 1 fibrosis, and had stable immunosuppression for at least 3 months.
Patients received either nonpegylated interferon 3 times weekly or pegylated interferon in combination with ribavirin in standard doses. Treatment was continued for 52 weeks after patients became HCV-negative.
According to Dr. Brown, of the 241 patients, 66 were treated, 22 achieved sustained virologic response, and only 2 (8%) relapsed. "A relapse rate of 8% is quite a bit lower than the 30% that is commonly cited in the literature," she told Medscape Gastroenterology.
She also noted that patients who achieved sustained virologic response were more likely to have had extended treatment than those who did not (97.5 vs 59.9 weeks; P < .014).
Moreover, "35% of the patients who went on to have a sustained virologic response actually became virus-negative after week 24," Dr. Brown said. "This suggests that even if patients are positive at 24 weeks, there is still a 35% chance that they can achieve sustained viral clearance."
Stuart C. Gordon, MD, also from the Department of Gastroenterology and
Transplant Surgery at the
"In light of these findings, our preconceived notions about antiviral therapy need to be re-explored," he concluded.
The study was funded by Henry Ford Health System in
The Liver Meeting 2009: American Association for the Study of Liver Diseases
(AASLD) 60th Annual Meeting: Abstract 187. Presented
Ocera Therapeutics Presents Clinical Data Demonstrating AST-120 Relieves Pruritus in Patients with Liver Cirrhosis at the 60th Annual AASLD Meeting
Ocera Therapeutics
Presents Clinical Data Demonstrating AST-120 Relieves Pruritus in Patients with
Liver Cirrhosis at the 60th Annual AASLD Meeting AST-120 Also Shown to Reduce
Ammonia and Brain Swelling in Rat Model of Cirrhosis
Patients treated with AST-120 had a statistically significant reduction in itch with a four-week treatment course. The benefit was seen as early as the first week of therapy and continued to improve over the four weeks of treatment. Mean reduction in pruritus by 100mm VAS at Week 4 was 30mm for AST-120 treated subjects vs. 5mm for placebo treated subjects, p=0.03. The reduction in itch was significantly correlated with a reduction in serum bile acids, which are thought to play a key role in the pathogenesis of pruritus in this patient population.
"Pruritus affects up to 15 percent of hepatitis C
patients, and can be devastating for chronic liver disease patients," said
Averell Sherker, M.D. Director of the Center for Liver Diseases at the
In a separate session at AASLD, Christopher Rose, Ph.D., Assistant Professor in the Department of Medicine at Universite de Montreal, presented the results of a preclinical study conducted with AST-120 in a rat model of cirrhosis. In that study, titled "AST-120 (spherical carbon adsorbent) attenuates brain edema and lowers arterial ammonia in bile-duct ligated rats," the administration of AST-120 resulted in a statistically significant reduction in serum ammonia levels and brain swelling. Increased serum ammonia is recognized as a central feature of hepatic encephalopathy and related complications.
The efficacy and safety of AST-120 in the treatment of MHE, the most frequent complication of cirrhosis, is currently being evaluated by Ocera in the ongoing ASTUTE Phase 2b study. MHE affects up to 60 percent of cirrhotic patients and is associated with neurocognitive deficits leading to an increased risk of car accidents, falls, loss of employment and reduced quality of life.
"AST-120 avidly binds ammonia, bile acids and many other potentially toxic substances from the lower gastrointestinal tract. In addition to showing great potential for the treatment of MHE and for the relief of pruritus, these data demonstrate AST-120 warrants further clinical evaluation for the treatment of other liver and gastrointestinal diseases," said Scott Harris, M.D. Ocera's Chief Medical Officer.
About AST-120
AST-120 is a novel proprietary microspherical carbon adsorbent
with a selective adsorption profile for a variety of unwanted substances in the
digestive tract. These substances may be responsible for a number of
conditions, including hepatic encephalopathy (HE), irritable bowel syndrome
(IBS), and pouchitis. The substances include ammonia, indoles (serotonin,
octopamine), histamine, secondary bile acids, advanced glycation endproducts (
About
Ocera Therapeutics, Inc.
Ocera Therapeutics, based in
Twice Daily Oral Medication Shows Promise in Treating Patients with Hepatitis C
Presented:
The INFORM-1 trial is randomized, double-blind, and placebo
controlled. The oral therapy was administered over a 14-day period, and the antiviral responses
were impressive among all groups. It was reported that the combination is
undergoing further development for treatment of chronic hepatitis C. "This
is the first study to demonstrate that an IFN-free, twice daily, combination
DAA regimen produces similar antiviral activity compared to triple therapy (
These results are very promising in regards of antiviral
potency and lack of resistance development. "From here we will need to
explore in a stepwise fashion if longer treatment will result in persistent
viral suppression, clear all HCV-infected hepatocytes and ultimately lead to a
sustained virologic response (
Abstract title:
Combination therapy with a nucleoside polymerase (R7128) and
protease (R7227/
Noninvasive Breath Test Predicts Survival in Patients with Viral Hepatitis
Presented
MELD (Model for End-Stage Liver Disease) is a scoring system adopted by the United Network for Organ Sharing to assess liver disease severity and determining 3-month mortality. Viral hepatitis progresses at an unpredictable rate and the addition of another way of assessing disease progression can serve as an important adjunct to MELD.
Researchers studied 395 patients
with viral hepatitis. The
They concluded that
Abstract title:
The noninvasive 13C methacetin breath test accurately predicts long-term survival in patients with chronic viral hepatitis and may serve as an adjunctive tool to MELD: Results of a 395-patient clinical trial.
BMY and ZGen
present Phase 1B results for PEG -Interferon
lambda in HCV patients
Bristol-Myers Squibb Company (NYSE:
The poster included data on 56
patients in the study. Antiviral activity was observed at all dose levels
tested. The results will be presented at the American Association for the Study
of the Liver Diseases annual meeting in
“There is a strong need for additional options for hepatitis C patients,” said Brian Daniels, M.D., senior vice president, Global Development & Medical Affairs, Bristol-Myers Squibb. “We are pursuing this investigational pathway to address the fact that although current interferons have been the backbone of therapy with meaningful efficacy, they are often poorly tolerated, leading to dose reductions, poor compliance and avoidance of treatment.”
“We are excited about the prospects
for
The Phase 1b clinical trial was
designed to evaluate the safety and antiviral activity of
In the single agent arm of the study with treatment-relapsed patients
Of the patients in the single agent arm of the study, all 12 of those patients receiving 1.5 mcg/kg and 3.0mcg/kg weekly for four weeks achieved a greater than 2 log decrease in HCV RNA. Five of the 12 patients receiving 1.5 mcg/kg and 3.00mcg/kg every two weeks for four weeks achieved a greater than 2 log decrease in HCV RNA.
At
Treatment-naive patients, who were treated with 1.5 mcg/kg of
The most common adverse events were
fatigue (29%) and nausea (13%). There were minimal effects on neutrophil
counts. Minimal constitutional symptoms or hematologic effects were observed
with
Overall, the results of the study support moving to dose-ranging Phase 2 studies in treatment-naïve HCV patients.
Avila AVL -181,
Demonstrating Viral Clearance of Hepatitis C Virus in Preclinical Models
Potential
for Rapid and Prolonged Therapeutic Benefit in HCV through Protein Silencing of
NS3 Protease
"Our
clinical candidate,
In one presentation,
"Potential for Rapid and Prolonged Therapeutic Benefit in HCV through
Protein Silencing of NS3 Protease with
· selectively bonds the HCV NS3 protease to completely and irreversibly inactivate proteolytic activity, essentially silencing the HCV protease complex;
· forms a highly specific covalent bond across HCV genotypes and clinically-described drug-resistant mutant proteases;
·
inhibits protease activity in cultured replicon
cells for >48 hours after very brief exposure and removal of
· demonstrates prolonged pharmacodynamic activity for both wild-type and drug-resistant mutations (e.g. R155K); and;
·
results in clearance of
HCV RNA from replicon cells in conjunction with a non-nucleoside polymerase
inhibitor, contributing to a profile that differentiates
In a second presentation, "
Protease Activity In Vivo that Directly Correlates with Prolonged Molecular
Target Occupancy", the data demonstrate that the orally available, novel HCV
protease
inhibitor,
· potently and irreversibly silences HCV proteases, and that the level of protease inhibition is directly correlated with the extent of target bonding;
· durably inhibits the HCV protease for at least 10 hours in vivo after a single exposure as measured in a novel model in which NS3/4A is expressed in the mouse liver; and
·
this duration of action coupled with the low
plasma levels of
About the Avilomics Platform and Covalent Drugs
The Avilomics platform is Avila`s powerful approach to design and develop covalent drugs that strongly, selectively, and resiliently bond to disease-causing proteins, thereby silencing their activity and producing superior pharmacological outcomes. Covalent drugs inherently provide prolonged duration of action through this silencing of the disease target, and they can solve the critical therapeutic challenges of drugging difficult targets and addressing resistance mutations. The three components of Avilomics are:
· Compositions: Innovative chemical structures for forming highly selective, not indiscriminate, covalent bonds
· Design: Proprietary informatics to uniquely identify sites amenable to selective covalent modification and target silencing
· Testing: Empirical methods to demonstrate covalent specificity at both target and proteomic levels
Together, these components provide a platform for efficient design and testing of covalent drugs. Avilomics opens up the broad potential of covalent drugs across target classes and disease areas, as demonstrated with the company`s emerging pipeline of novel, protein silencing covalent drugs.
About Avila Therapeutics, Inc.
GlobeImmune's Hepatitis C Therapeutic Vaccine Combined with Standard of Care Increases End of Treatment Response Rate by 15%
Phase
2b Data Presented at American Association for the Study of Liver Diseases
Meeting
LOUISVILLE,
CO--(Marketwire - November 2, 2009) - GlobeImmune Inc. will present Phase 2b
data today at the 60th Annual Meeting of the American Association for the Study
of Liver Diseases (AASLD) demonstrating that GI-5005, the Company's
investigational Tarmogen® product for hepatitis C virus (HCV) infection,
increased the end of treatment response in genotype 1 interferon-naïve patients
to 74% when used in combination with standard of care (
This ongoing Phase 2b study is
designed to compare GI-5005 plus
"The efficacy and safety data generated thus far in this trial are encouraging and suggest a potentially important role for this compound in the treatment of HCV," said Dr. McHutchison.
"We believe a robust immune response is necessary to clear HCV infected cells from the liver and these data suggest that stimulating a T-cell immune response with GI-5005 can have a meaningful impact on patient outcomes," said David Apelian, M.D., Ph.D., Chief Medical Officer at GlobeImmune. "Demonstrating that this therapeutic vaccine increased the complete response rate by 15% in this trial, without adding significant toxicities, represents an important scientific and medical advance."
The late-breaker poster (LB15)
titled, "GI-5005 Therapeutic Vaccine Plus
Peg-IFN/Ribavirin Improves End of Treatment Response at 48 Weeks Versus
Peg-IFN/Ribavirin in Naive Genotype 1 Chronic HCV Patients" will be
presented by Dr. McHutchison at the AASLD Meeting today from
The GI-5005-02 clinical trial is a randomized, multi-center, Phase 2 study evaluating 140 patients, all with chronic genotype 1 HCV infection. In the trial, 74 percent of the patients had never received prior treatment, and the remaining 26 percent experienced prior treatment failures.
GlobeImmune's GI-5005 is a Tarmogen designed to elicit an HCV-specific T-cell response. Tarmogens are whole, heat-killed recombinant S. cerevisiae yeast that express antigens from one or more disease-related proteins.
About GlobeImmune
GlobeImmune Inc. is a private company developing active immunotherapies called Tarmogens for the treatment of cancer and infectious diseases. Tarmogens generate activated killer T cells intended to locate and eliminate cancer cells and/or virally-infected cells. The Company's lead product candidate, GI-5005, is a Tarmogen being developed for the treatment of chronic hepatitis C infection (HCV). GI-5005 is designed to complement both the current standard of care and emerging novel therapies for HCV. The company's lead oncology program, GI-4000, targets cancers caused by mutated versions of the Ras oncoprotein. GI-4000 is being investigated in clinical trials for the treatment of pancreas cancer as well as other cancers that contain mutated Ras, including non-small cell lung cancer and colorectal cancer. In May 2009, the Company announced a global partnership with Celgene focused on the discovery, development and commercialization of multiple product candidates for the treatment of cancer.
For additional information, please visit the company's Web site at www.globeimmune.com.
Pharmasset to Webcast an Investor Event from the AASLD Meeting
PRINCETON, N.J., Nov. 1 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) today announced that it will webcast an investor event from the American Association for the Study of Liver Diseases (AASLD) on Monday, November 2, 2009 starting at 7:00pm ET. During this webcast, management will review Pharmasset's progress on the programs that are the subject of presentations at AASLD.
To access a simultaneous webcast of
this event via the internet, log on to the "Events &
Presentations" section of the
·
Late
Breaker Abstract 17 – "Antiviral Activity, Pharmacokinetics, Safety,
and Tolerability of
RG7128/INFORM-1
·
Abstract
1585 – "Combination Therapy with Nucleoside Polymerase R7128 and
Protease R7227/
·
Abstract
193 – "Combination Therapy With A Nucleoside Polymerase (R7128) And
Protease (R7227/
·
Abstract
1594 – "Pharmacokinetics/Pharmacodynamics (PK/PD) of Combination R7227
and R7128 Therapy From INFORM-1 Demonstrates Similar
Early HCV Viral Dynamics When R7227 is Combined With Either
·
Abstract
1605 – "Novel 2 -F-2 -C-Methylpurine Nucleotide Analogs Are
Active Inhibitors of HCV Replication And Lack Cross-Resistance with Other Nucleos(t)ide Analogs" will be presented in a poster
session on Tuesday November 3rd at
About Pharmasset
Pharmasset is a clinical-stage
pharmaceutical company committed to discovering, developing, and
commercializing novel drugs to treat viral infections. Pharmasset's primary
focus is on the development of oral therapeutics for the treatment of hepatitis
C virus (HCV) and, secondarily, on the development of Racivir(TM) for the
treatment of human immunodeficiency virus (HIV). Our research and development
efforts focus on nucleoside/tide analogs, a class of compounds which act as
alternative substrates for the viral polymerase thus inhibiting viral
replication. We currently have three clinical-stage product candidates. RG7128,
a nucleoside analog for chronic HCV infections, is in a Phase 2b clinical trial
in combination with Pegasys(R) plus Copegus(R) and is also in INFORM studies,
the first series of studies designed to assess the potential of combinations of
small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These
clinical studies are being conducted through a strategic collaboration with
Roche. Our other clinical stage candidates are
African Americans Fare Worse After Undergoing Liver Transplantation Due to Hepatitis C
Presented
This retrospective multisite cohort study of 771 patients from 5 sites evaluated patients who had a liver transplantation between 1999 and 2008. All patients were transplanted due to liver failure caused by HCV. Data were analyzed at 6 months, 1 year, and 2 years after transplantation.
The researchers found, based on an analysis of liver biopsies performed after transplantation, that African Americans had more severe fibrosis progression and histologic inflammation compared to whites following liver transplantation for HCV. While Hispanics demonstrated similar disease progression after liver transplantation as whites, African Americans more often experienced graft failure and required repeat liver transplantation compared to whites. In addition, the hazard ratio for patient death for African Americans was 1.3, indicating a 30% higher mortality for African Americans compared to whites. The researchers concluded that African Americans who undergo liver transplantation caused by HCV had more severe fibrosis progression and histologic inflammation compared to whites undergoing the same procedure.
"While this study illustrates that HCV histologic progression occurs early and is more aggressive in African Americans, it does not allow a careful analysis of factors that may be contributing to these differences," concluded Dr. Layden, "we are conducting a multi-site prospective study to not only confirm these retrospective findings, but also examine both donor and host factors, including psychosocial, virologic, genetic and immunologic that may contribute to this important health disparity."
Abstract title:
Hepatitis C virus (HCV) progresses more rapidly after orthotopic liver transplantation (OLT) in African-Americans (AA) compared to whites (W)
Schering hep C drug promising in Phase II study
By Bill Berkrot
* Boceprevir rapid responders reach 82
pct
* 55
pct
The triple combination of boceprevir and the current treatments of
pegylated-interferon and ribavirin appeared to knock out the virus at double
the rate of the standard drugs alone, according to researchers.
Among patients who had a rapid response to the combination therapy, the cure
rate, or those in whom the virus remained undetectable after completing
treatment, exceeded 80 percent, according to data to be presented at the
American Association for the Study of Liver Diseases (AASLD) meeting in
Boceprevir is in a race with Vertex Pharmaceuticals Inc's telaprevir to
become the first of a next generation of antiviral hepatitis C medicines called
protease inhibitors. Both appear to be highly promising advances in the
treatment of the serious liver disease based on early clinical results.
"The next decade for hepatitis C not only holds substantial promise for
those who have not been treated, but those who have already been treated with
standard of care also look like they are going to derive substantial benefits
from this new generation of therapies," Dr Paul Kwo, lead investigator of
the boceprevir study, said in an interview.
The 595-patient boceprevir study was designed to test the triple combination
in a response guided therapy. The idea is to enable physicians to tailor
duration of therapy -- either 28 or 48 weeks -- based on a patient's early
response to treatment, and to help cut the risk of developing resistance to the
drug.
All patients in the the study received the standard drugs for four weeks
before adding boceprevir, which is given three time a day, in order to
determine the level of response to the current drugs before the triple
combination therapy began.
Among the null responders, 25 percent of patients who received 28 weeks of
therapy achieved sustained viral response (
The percentage of patients in whom the virus is undetectable at least 24
weeks after completing treatment yields the critical measure known as sustained
viral response, or
The 55 percent response was impressive, Kwo said, because "these are
the individuals who are the most difficult to treat in our clinics."
Among patients who had a rapid viral response -- defined as the virus being
cleared after the initial four-week lead-in treatment plus four weeks on the
triple combination -- there was an 82 percent
Patients who did not have a rapid viral response but reached undetectable
virus levels by treatment week 16 (up to 12 weeks of therapy including
boceprevir) had a 79 percent
By comparison, those who received only the standard drugs for 48 weeks had a
38 percent
The ability to successfully treat patients for 28 weeks rather than 48 would
be a huge advantage as current drugs can be difficult to tolerate and often
lead to flu-like symptoms for the duration of the treatment period.
The most common adverse events in patients
receiving boceprevir were fatigue, anemia, nausea and headache. While anemia
occurred in about half the patients, incidence of discontinuation due to anemia
was "extremely low," Kwo said.
"It's very exciting data, but larger studies will have to confirm what we see as signals in this very small but promising study," Kwo said. (Reporting by Bill Berkrot; editing by Andre Grenon))
Phase
Post-transplant Prophylactic Antiviral Treatment Does Not Prevent Recurrent Hepatitis C: Presented at AASLD
By Cheryl Lathrop
BOSTON -- November 1, 2009 -- Post-transplant prophylactic antiviral treatment
with pegylated interferon (
Natalie Bzowej, MD,
Recurrent allograft hepatitis due to hepatitis C virus (HCV) can be aggressive
and can result in graft loss. Prevention of allograft hepatitis C by
post-transplant prophylaxis with antiviral treatment is desirable and
The prospective, multicentre, open-label, randomised study compared
prophylactic treatment with a low accelerating dose regimen of
Patients were aged >=18 years and had undergone orthotopic liver
transplantation (OLT) due to liver disease from HCV infection. Patients were
clinically stable and expected to be able to tolerate
At 10 to 26 weeks post transplant, patients were randomised to either the
prophylaxis arm (n = 55) which consisted of
The primary endpoint was the percentage of patients with histologically
confirmed HCV recurrence at 120 weeks postrandomisation. Secondary endpoints
included Histological Activity Index (
There was no difference between the study arms in the primary endpoint of
histologically confirmed HCV recurrence at 120 weeks. The distribution of
Virologic response rates were generally similar between the 2 arms. Three
patients in each arm had biopsy-proven acute allograft rejection by week 120.
The frequency of adverse events was generally similar between the 2 arms.
"Given the significant toxicity associated with
[Presentation Title: A Randomized Controlled Trial of the Efficacy,
Tolerability, and Safety of Prophylactic Treatment With
Peginterferon alfa-2a Plus Ribavirin After Orthotopic Liver Transplantation
(OLT) for Hepatitis C: The
More Than 80 Percent of HCV Genotype 1 Treatment-Naive Patients Achieved Sustained Virologic Response With Twice-Daily Telaprevir-Based Regimen
Phase II telaprevir data from Tibotec
featured in oral presentation at AASLD
Cork, Ireland (October 31, 2009) –Tibotec announced today results of a new
study (VX950-C208), which showed that sustained virologic response (
In the phase II study, which enrolled 161 treatment-naïve genotype 1 patients,
rates of
For the vast majority of patients, these high
Approximately 180 million people worldwide are infected with HCV,1
the most common cause of liver transplant in Europe.2 People with
HCV genotype 1 currently face treatment limitations, including a standard of
care that cures just 40 to 50 percent of patients.3 Without
effective treatment, HCV can lead to serious and fatal diseases of the liver,
including liver cancer4.
“The data presented today show that a significant number of treatment-naïve
genotype 1 HCV patients achieved sustained virologic response with telaprevir,
in combination with standard of care,” said professor Patrick Marcellin from
Hôpital Beaujon in Clichy, France. “Telaprevir, which directly targets the
virus by aiming to block its replication, could allow shortening treatment
duration and increasing cure rates in people with HCV, [compared to standard of
care] offering a new approach to treating HCV.”
About Telaprevir C208 study in Treatment-Naïve Patients
The phase IIa, open-label, randomised study evaluated telaprevir administered
every eight hours or every 12 hours in combination with standard of care
Peg-IFN alfa-2a (Pegasys®) and ribavirin (Copegus®) or
Peg-IFN alfa2b (PegIntron®) and ribavirin (Rebetol®) in
treatment-naïve patients with chronic genotype 1 HCV infection.
The objective of the trial was to explore the efficacy, safety, tolerability,
pharmacokinetics, and pharmacokinetic-pharmacodynamic relationships of
telaprevir when administered as 750 mg every eight hours or 1125 mg every 12
hours in combination with Pegasys and Copegus or PegIntron and Rebetol. A total
of 161 subjects were randomised to the following groups:
A: Telaprevir 750 mg q8h with Pegasys/Copegus
(Tq8h/Peg2-a) (n=40)
B: Telaprevir 750 mg q8h with PegIntron/Rebetol (Tq8h/Peg2-b) (n=42)
C: Telaprevir 1125 mg q12h with Pegasys/Copegus (Tq12h/Peg2-a) (n=40)
D: Telaprevir 1125 mg q12h with PegIntron/Rebetol (Tq12h/Peg2-b) (n=39)
All subjects received 12 weeks of telaprevir treatment in combination with
standard therapy. At the end of Week 12, telaprevir dosing was completed and
subjects continued on standard therapy only. Most subjects achieved Rapid
Virological Response (RVR) (undetectable at week 4) and remained undetectable
until week 20 and were allowed to stop all treatment at week 24. Only 18% of
subjects were required to continue standard treatment up to week 48.
Following are the efficacy findings, as measured by sustained viral response
rates (SVRs):
- 85 percent of patients
taking telaprevir 750 mg q8h with Tq8h/Peg2-a achieved
- 81 percent of patients taking
telaprevir 750 mg q8h with Tq8h/Peg2-b achieved
- 82.5 percent of patients
taking telaprevir 1125 mg q12h with Tq12h/Peg2-a achieved
- 82.1 percent of patients
taking telaprevir 1125 mg q12h with Tq12h/Peg2-b achieved
The pharmacokinetic/pharmacodynamic analysis showed that total exposure to
telaprevir (measured as AUC24h) was similar across all groups.
AEs were similar to those observed in other trials with Telaprevir.
Serious AEs leading to permanent treatment discontinuation of all drugs were
mainly related to rash (3%, 4/161) and anemia (2%, 3/161).
“For too long, people with HCV have faced treatment limitations, necessitating
a paradigm shift in HCV therapy,” said Roger Pomerantz, MD, President of
Tibotec Research and Development. “Tibotec is proud to apply its
expertise in virology to discover, develop and make available new therapies
that target HCV in a different way.”
About Telaprevir
There are currently two fully enrolled, pivotal phase 3 clinical trials
examining telaprevir in genotype 1 HCV-infected adults – REALIZE in
treatment-experienced patients and ADVANCE in treatment-naïve patients.
REALIZE is the only ongoing phase 3 study comparing the efficacy of a regimen
containing a
Tibotec has the right to develop and commercialise telaprevir in
About Tibotec BVBA
Tibotec BVBA is a global pharmaceutical and research development company. The
Company’s main research and development facilities are in