<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_277"
                     title="Liver Cell Culture System Might Test New HCV Drugs (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265817320759"
                     
      &lt;p&gt;Researchers say they can now grow liver cells that maintain their functions long enough to test potential treatments for hepatitis C.&lt;/p&gt;
&lt;p&gt;The method uses so-called &quot;micropatterned co-cultures&quot; of primary human hepatocytes and supportive stroma, according to Sangeeta N. Bhatia, MD, PhD, of MIT, and colleagues.&lt;/p&gt;
&lt;p&gt;The co-cultures were able to support the entire life cycle of hepatitis C, including infection and replication, Bhatia and colleagues reported online in the &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Coupled with reporter systems, the co-cultures have &quot;potential as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity&quot; of antiviral drugs, the researchers said.&lt;/p&gt;
&lt;p&gt;The lack of such a system has been a roadblock to testing potential treatments for the virus, which affects 130 million people around the world, the researchers noted in the journal.&lt;/p&gt;
&lt;p&gt;Recently, they added, researchers have been able to propagate the virus in human hepatoma cells, but those cells, among other issues, proliferate abnormally and have disturbed gene expression.&lt;/p&gt;
&lt;p&gt;To overcome those obstacles, the researchers turned to primary hepatocytes, which would make a better test system, except that they are notoriously hard to maintain in culture.&lt;/p&gt;
&lt;p&gt;To form the co-cultures, Bhatia and colleagues seeded multi-well plates with human hepatocytes, followed several hours later by murine fibroblasts.&lt;/p&gt;
&lt;p&gt;&quot;If you just put cells on a surface in an unorganized way, they lose their function very quickly,&quot; Bhatia said in a statement. &quot;If you specify which cells sit next to each other, you can extend the lifetime of the cells and help them maintain their function.&quot;&lt;/p&gt;
&lt;p&gt;In a series of experiments, Bhatia and colleagues found:&lt;ul&gt; &lt;li&gt;Pseudoparticles bearing the hepatitis C glycoproteins E1 and E2 were able to infect between 1% and 3% of the hepatocytes, but did not infect the fibroblasts.&lt;/li&gt; &lt;li&gt;A hepatitis C virus modified to express a fluorescent protein persistently replicated over a two-week period.&lt;/li&gt; &lt;li&gt;Infectious virus was found in the co-culture supernatant from four through 12 days after initial infection.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The researchers also tested some possible therapeutics, including antibodies against viral entry factors and viral protease inhibitors, and were able to show effects on replication of hepatitis C.&lt;/p&gt;
&lt;p&gt;They were also able to test two or more drugs simultaneously to show the feasibility of combination drug studies using the system.&lt;/p&gt;
&lt;p&gt;Although the system is &quot;an important step forward,&quot; Bhatia and colleagues said, the co-cultures have some limitations, including the relatively inefficient uptake of virus.&lt;/p&gt;
&lt;p&gt;But they concluded that the co-cultures have the potential to be a &quot;highly valuable system for studies of (hepatitis C) biology.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;This study had support from the Greenberg Medical Research Institute, the Ellison Medical Foundation, the Starr Foundation, the Ronald A. Shellow Memorial Fund, the Richard Salomon Family Foundation, and the NIH. The researchers said they had no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_3520"
                     title="AASLD: Once-Daily HCV Protease Inhibitors Show Early Promise (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/AASLD/tb/16766?impressionId=1265817320759"
                     
      BOSTON  --  Two investigational drugs targeting the hepatitis C virus (HCV) protease enzyme helped patients clear the virus with once-daily dosing, contrasting with the three-times-per-day schedule needed for similar drugs in development, researchers reported here in separate studies.&lt;br&gt;
&lt;br&gt;At least 85% of patients adding narlaprevir (formerly called SCH 900518) to pegylated interferon-alfa-2b (PEGIntron) and ribavirin (Rebetol) after four weeks achieved rapid virological responses, compared with no patients receiving only interferon and ribavirin, according John Vierling, MD, of Baylor College of Medicine in Houston.&lt;br&gt;
&lt;br&gt;Early virologic responses, defined as viral clearance after 12 weeks of treatment, also occurred in 85% to 87% of patients receiving narlaprevir after the interferon-ribavirin lead-in, versus 17% of patients in the control arm.&lt;br&gt;
&lt;br&gt;Comparable results were reported for another investigational compound, BI 201355, by Mark Sulkowski, MD, of Johns Hopkins University. The drug, also given once daily with interferon-ribavirin, led to HCV RNA becoming undetectable by week 12 in up to 90% of patients.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Vierling and Sulkowski reported interim results from ongoing Phase II trials of the two drugs here in a late-breaking abstract session at the American Association for the Study of Liver Disease&apos;s annual meeting.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Narlaprevir&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;By itself, narlaprevir is eliminated rapidly from circulation, as are boceprevir and telaprevir, the HCV protease inhibitors farthest along in development (now in Phase III testing). Those drugs must be given three times daily. Vierling said the multiple dosing schedule is a source of compliance problems for HCV-infected patients.&lt;/p&gt;
&lt;p&gt;But co-administering narlaprevir with 100 mg of the anti-HIV drug ritonavir  --  one-twelfth the dose normally given to HIV patients  --  interferes with narlaprevir&apos;s metabolism by the CYP3A4 enzyme, prolonging its half-life enough that a single daily dose is feasible, Vierling said.&lt;/p&gt;
&lt;p&gt;In the current study, called NEXT-1, several permutations of the narlaprevir-ritonavir and interferon-ribavirin combinations are being tested.&lt;/p&gt;
&lt;p&gt;The study has enrolled 111 patients, all with HCV genotype 1.&lt;/p&gt;
&lt;p&gt;Three dose levels of narlaprevir (200 or 400 mg once daily or 100 mg twice daily), combined with 100 mg of ritonavir, were initiated simultaneously with pegylated interferon and ribavirin at standard doses.&lt;/p&gt;
&lt;p&gt;Two other treatment arms were established in which the two once-daily doses of narlaprevir plus ritonavir were started after patients had been on the interferon-ribavirin combination for four weeks.&lt;/p&gt;
&lt;p&gt;A sixth group took only interferon and ribavirin, which is the current standard of care for HCV antiviral treatment.&lt;/p&gt;
&lt;p&gt;In the five groups receiving narlaprevir, the drug was given for 12 weeks, with interferon and ribavirin continued for an additional 12 or 36 weeks, depending on patients&apos; virologic responses after the first four weeks of treatment.&lt;/p&gt;
&lt;p&gt;In the two arms involving delayed narlaprevir, virologic clearance within four weeks occurred in 85% to 87% of patients, Vierling reported.&lt;/p&gt;
&lt;p&gt;Starting narlaprevir and ritonavir simultaneously with interferon and ribavirin appeared to be a less successful strategy, with 58% to 75% of patients in those arms achieving rapid virologic responses.&lt;/p&gt;
&lt;p&gt;Vierling said that dosing narlaprevir twice daily actually reduced its efficacy, presumably because maximal plasma levels of the drug were about half those seen with the once-daily administration of higher doses.&lt;/p&gt;
&lt;p&gt;Mild to moderate anemia and mild neutropenia were the main adverse events that appeared to be related to the narlaprevir-ritonavir treatment. Vierling said no patients discontinued treatment because of anemia, and the neutropenia had no clinical consequences.&lt;/p&gt;
&lt;p&gt;Dizziness was also seen more often with narlaprevir, but also was relatively mild, Vierling said.&lt;/p&gt;
&lt;p&gt;Other adverse effects, such as fatigue, nausea, headache, and skin rashes occurred in the control arm and with narlaprevir.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;BI 201355&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;The other once-daily protease inhibitor described here, BI 201355, does not require co-administration of another agent to keep it active for a full day.&lt;/p&gt;
&lt;p&gt;Sulkowski reported that the drug led to rapid virological responses in most patients, with 62% to 77% showing viral clearance within four weeks of starting the drug.&lt;/p&gt;
&lt;p&gt;Unlike narlaprevir, however, a four-week lead-in with interferon and ribavirin did not boost BI 201355&apos;s effectiveness. The highest response rates at weeks four and 12 were seen with 240 mg of the drug started simultaneously with interferon-ribavirin, at 77% and 90%, respectively.&lt;/p&gt;
&lt;p&gt;Response rates among patients receiving the same dosage of BI 201355 with the four-week lead-in were 62% and 80%, respectively.&lt;/p&gt;
&lt;p&gt;Approximately 450 patients took part in the four-arm trial, which also included a control group receiving only interferon and ribavirin. Viral clearance after four and 12 weeks in the control group was seen in 4.2% and 42% of patients, respectively, significantly lower than in the groups taking BI 201355 (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05).&lt;/p&gt;
&lt;p&gt;As in the NEXT-1 trial, all patients had HCV genotype 1.&lt;/p&gt;
&lt;p&gt;Sulkowski said skin rashes were the chief adverse effects of concern with the drug. Most cases were mild and patients were able to stay on the drug. But 27% to 33% of patients in the higher-dose BI 201355 groups developed rashes, compared with about 13% of the control group.&lt;/p&gt;
&lt;p&gt;Jaundice was also seen in up to 20% of patients treated with BI 201355. Less than 2% of the control patients developed the condition.&lt;/p&gt;
&lt;p&gt;Scott Friedman, MD, of Mount Sinai School of Medicine in New York City, who was not involved in the study, said he was skeptical about the need for once-daily dosing in HCV infected patients.&lt;/p&gt;
&lt;p&gt;He said his experience is that most patients understand the importance of keeping to their dosing schedules.&lt;/p&gt;
&lt;p&gt;&quot;The patients I see, they get it,&quot; Friedman said.&lt;/p&gt;
&lt;p&gt;But he added that compliance may be more of a problem with new patients, compared with those who have been on therapy for a while.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The narlaprevir study was funded by Schering-Plough.&lt;/p&gt;&lt;p&gt;The BI 201355 study was funded by Boehringer Ingelheim.&lt;/p&gt;&lt;p&gt;Vierling reported relationships with Schering-Plough, Abbott, Bristol-Myers Squibb, Gilead, Roche, Salix, Vertex, Hepa-Life Technologies, Arbios Systems, Axcan, Indenix, Novartis, Wyeth, GlobeImmune, Zymogenetics, Ocera, Intercept, Conatus, Pharmasset, and Pfizer.&lt;/p&gt;&lt;p&gt;Several co-authors were employees of Schering-Plough.&lt;/p&gt;&lt;p&gt;Sulkowski reported relationships with Boehringer Ingelheim, Roche, Schering, Merck, Human Genome Sciences, Gilead, Vertex, Tibotec, Bristol-Myers Squibb, Pfizer, Medarex, Peregrine, Debiopharm, and Abbott. Several co-authors were employees of Boehringer Ingelheim.&lt;/p&gt;&lt;p&gt;Friedman reported relationships with Exalenz, sanofi-aventis, Axcan, Angion, Intercept, 7TM, Stromedix, and Celera.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_3563"
                     title="AASLD: HCV Response Linked Strongly to Gene Variant (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/AASLD/tb/16829?impressionId=1265817320759"
                     
      &lt;p&gt;BOSTON  --  Additional analysis has confirmed that a polymorphism in an interferon-related gene is strongly associated with responses to standard treatments for hepatitis C virus (HCV) infection, a researcher said here.&lt;/p&gt;
&lt;p&gt;Not only is the so-called CC variant of the &lt;em&gt;IL28B&lt;/em&gt; 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 Duke University.&lt;/p&gt;
&lt;p&gt;Thompson was part of a group that, in August, reported online in &lt;em&gt;Nature&lt;/em&gt; that the CC genotype of &lt;em&gt;IL28B&lt;/em&gt;, which encodes the lambda-3 form of interferon, is associated with sustained suppression of HCV. (See &lt;a href=&quot;http://www.medpagetoday.com/InfectiousDisease/Hepatitis/15564&quot; mce_href=&quot;http://www.medpagetoday.com/InfectiousDisease/Hepatitis/15564&quot; target=&quot;_blank&quot;&gt;Gene Variant Predicts HCV Treatment Success&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Speaking here at the American Association for the Study of Liver Diseases meeting, Thompson reported on further analyses of the group&apos;s data, focusing on virologic responses after four and 12 weeks, referred to as rapid and early responses, respectively.&lt;/p&gt;
&lt;p&gt;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.&lt;/p&gt;
&lt;p&gt;As in the &lt;em&gt;Nature&lt;/em&gt; 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.&lt;/p&gt;
&lt;p&gt;As Thompson reported here, sustained virologic response rates in patients with the CC genotype of &lt;em&gt;IL28B&lt;/em&gt; 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.&lt;/p&gt;
&lt;p&gt;Those ranged from 27% to 33% in whites, 13% to 15% in blacks, and 27% to 38% in Hispanics.&lt;/p&gt;
&lt;p&gt;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.&lt;/p&gt;
&lt;p&gt;Other baseline factors predicting sustained response rates included viral loads, white or Hispanic versus black ethnicity, baseline liver fibrosis, and fasting blood sugar.&lt;/p&gt;
&lt;p&gt;Thompson said the &lt;em&gt;IL28B&lt;/em&gt; 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.&lt;/p&gt;
&lt;p&gt;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 log&lt;sub&gt;10&lt;/sub&gt; reductions in viral loads of 2.5, whereas white patients with the other genotypes had not yet achieved one-log reductions.&lt;/p&gt;
&lt;p&gt;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.&lt;/p&gt;
&lt;p&gt;The same pattern was seen in African-Americans and Hispanics, he said.&lt;/p&gt;
&lt;p&gt;Another new finding was that the CC genotype predicted sustained responses in white patients who had not shown viral clearance by week four.&lt;/p&gt;
&lt;p&gt;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%).&lt;/p&gt;
&lt;p&gt;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 (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), Thompson said.&lt;/p&gt;
&lt;p&gt;Other researchers said the findings, when validated, would likely be practice-changing.&lt;/p&gt;
&lt;p&gt;Scott Friedman, MD, president of AASLD and a hepatologist at Mount Sinai School of Medicine in New York City, predicted that &lt;em&gt;IL28B&lt;/em&gt; genotype testing would become part of the standard of care once a test becomes clinically available.&lt;/p&gt;
&lt;p&gt;Schering-Plough, which sells pegylated interferon-alfa-2b (PEGIntron), owns commercial rights to develop the genotype test.&lt;/p&gt;
&lt;p&gt;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.&lt;/p&gt;
&lt;p&gt;He said the company had discussed nonexclusive licensing arrangements with other firms with the relevant capabilities, but no decisions had been made.&lt;/p&gt;
&lt;p&gt;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.&lt;/p&gt;
&lt;p&gt;Thompson agreed that the &lt;em&gt;IL28B&lt;/em&gt; polymorphism&apos;s effect on treatment response would have to be reevaluated for regimens including direct antivirals.&lt;/p&gt;
&lt;p&gt;Other research needs include studies of the polymorphism in patients with nongenotype 1 HCV and whether it predicts responses to personalized duration of therapy.&lt;/p&gt;
&lt;p&gt;In his presentation here, Thompson offered no new insights into the mechanism underlying the &lt;em&gt;IL28B&lt;/em&gt; polymorphism&apos;s effects on treatment responses, beyond what the &lt;em&gt;Nature&lt;/em&gt; paper had suggested  --  namely, that interferon-lambda-3 helps mediate innate control of HCV.&lt;/p&gt;
&lt;p&gt;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.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The IDEAL study was funded by Schering-Plough.&lt;/p&gt;&lt;p&gt;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, Gilead, Vertex, Globimmune, Human Genome Sciences, Boehringer Ingelheim, GlaxoSmithKline, Tibotec, Novartis, Pharmasset, Salix, Pfizer, and Bristol-Myers Squibb, among others.&lt;/p&gt;&lt;p&gt;Friedman reported relationships with Exalenz, sanofi-aventis, Axcan, Angion, Intercept, 7TM, Stromedix, and Celera.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_3587"
                     title="AASLD: High SVR Rates Seen with Telaprevir for Hepatitis C (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/AASLD/tb/16859?impressionId=1265817320759"
                     
      &lt;p&gt;BOSTON  --  Availability of direct antiviral drugs for hepatitis C virus (HCV) infection moved another step closer to realization, with favorable results reported here for the investigational drug telaprevir in two Phase II studies.&lt;/p&gt;
&lt;p&gt;In a trial with patients who had failed to obtain satisfactory responses to pegylated interferon and ribavirin (Rebetol), sustained virologic responses were seen in up to 53% of patients who had telaprevir added to the two standard drugs, reported John G. McHutchison, MD, of Duke University.&lt;/p&gt;
&lt;p&gt;And another study, in which the drug was given twice a day (along with interferon and ribavirin) instead of the three-times-daily regimen used in other telaprevir trials, found sustained virologic response rates upwards of 80% in treatment-naive patients, said Patrick Marcellin, MD, of Beaujon Hospital in Clichy, France.&lt;/p&gt;
&lt;p&gt;Both trials were reported here at the American Association for the Study of Liver Diseases annual meeting.&lt;/p&gt;
&lt;p&gt;Telaprevir is one of several HCV protease inhibitors making their way through the development pipeline. Along with a similar drug called &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/AASLD/16763&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/AASLD/16763&quot; target=&quot;_blank&quot;&gt;boceprevir&lt;/a&gt;, it is the most advanced, with Phase III studies now underway.&lt;/p&gt;
&lt;p&gt;They&apos;re widely expected to be the first direct antiviral drugs made available for HCV, with FDA approval possible in 2011.&lt;/p&gt;
&lt;p&gt;McHutchison presented data from a study called PROVE3 that randomized 453 patients with HCV genotype 1 to one of four treatments, three of which included telaprevir.&lt;/p&gt;
&lt;p&gt;Patients in PROVE3 had received a previous course of treatment with interferon and ribavirin but either did not have viral loads reduced to undetectable levels or relapsed following an initial response.&lt;/p&gt;
&lt;p&gt;The best sustained virologic response rates in the trial were seen with the two regimens that combined telaprevir with interferon and ribavirin.&lt;/p&gt;
&lt;p&gt;In one, patients received telaprevir for 12 weeks and interferon and ribavirin for 24 weeks; the other regimen provided telaprevir for 24 weeks and interferon-ribavirin for 48 weeks.&lt;/p&gt;
&lt;p&gt;Sustained virologic responses were obtained by 51% and 53% of patients in those groups, respectively, compared with 14% among patients given interferon and ribavirin for 48 weeks.&lt;/p&gt;
&lt;p&gt;In the fourth group, treated with telaprevir and pegylated interferon for 24 weeks, and no ribavirin, the sustained response rate was 24%.&lt;/p&gt;
&lt;p&gt;Rates for all three telaprevir regimens were significantly higher than the interferon-ribavirin control arm (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.03).&lt;/p&gt;
&lt;p&gt;Patients who had had prior relapses did much better than those who had not responded at all to standard treatment, McHutchison said, with sustained response rates of up to 76% versus less than 40% for prior nonresponders.&lt;/p&gt;
&lt;p&gt;McHutchison said viral breakthroughs during treatment were markedly higher with the regimen that included telaprevir but omitted ribavirin than with any of the other three.&lt;/p&gt;
&lt;p&gt;He also said that when patients obtained sustained responses, they were maintained for an additional 24 weeks in nearly every case.&lt;/p&gt;
&lt;p&gt;All the telaprevir regimens in PROVE3 gave the drug three times a day, but Marcellin reported results from another trial that tested a twice-daily schedule.&lt;/p&gt;
&lt;p&gt;Dubbed C208, the 161-patient randomized study compared two regimens in which the drug was given every eight hours to two regimens with telaprevir given every 12 hours.&lt;/p&gt;
&lt;p&gt;All four treatments also included pegylated interferon and ribavirin. Telaprevir was given for 12 weeks in all treatment arms, with interferon and ribavirin continued for 12 or 36 additional weeks depending on virologic response.&lt;/p&gt;
&lt;p&gt;Patients were previously untreated and were infected with HCV genotype 1.&lt;/p&gt;
&lt;p&gt;Marcellin reported virtually identical sustained virologic response rates for all four treatment arms, from 81% to 85%.&lt;/p&gt;
&lt;p&gt;Some patients received pegylated interferon-alfa-2a (Pegasys) and some received the alfa-2b version (PEGIntron), but sustained response rates did not differ between these forms of interferon.&lt;/p&gt;
&lt;p&gt;Response rates at treatment week four also did not differ markedly between treatment groups, and did not differ at all between the eight-hour and 12-hour dosing schedules.&lt;/p&gt;
&lt;p&gt;Patients receiving the alfa-2a form had rapid response rates of about 80%, whereas just under 70% of those receiving the alfa-2b version had responses at week four.&lt;/p&gt;
&lt;p&gt;In both studies, anemia and skin rashes and pruritus were relatively common. McHutchison reported that 18 patients in the three telaprevir arms in PROVE3 discontinued treatment because of the skin problems, whereas there were no discontinuations in the standard-of-care group for those symptoms.&lt;/p&gt;
&lt;p&gt;Three patients withdrew because of anemia, which also drove one patient in the interferon-ribavirin arm out of the study.&lt;/p&gt;
&lt;p&gt;However, with 350 patients in the three telaprevir arms, the rate of discontinuations was not unusually high, McHutchison suggested. The numbers and types of adverse events &quot;were similar to those reported in prior Phase II studies,&quot; he said.&lt;/p&gt;
&lt;p&gt;Marcellin said rashes, pruritus, and anemia each affected about half of patients in each treatment group, with no difference between the eight-hour and 12-hour dosing groups.&lt;/p&gt;
&lt;p&gt;Scott Friedman, MD, president of AASLD and a hepatologist at Mount Sinai School of Medicine in New York City, said the PROVE3 results were especially compelling.&lt;/p&gt;
&lt;p&gt;He said treatments for patients who fail or relapse with standard interferon-ribavirin therapy are currently lacking.&lt;/p&gt;
&lt;p&gt;&quot;I have a lot of patients who have tried and failed, and they&apos;re desperate for therapy,&quot; he said. &quot;From a practical perspective, these are the patients we&apos;re anxious to help.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Both studies were funded by Vertex and Tibotec, developers of telaprevir.&lt;/p&gt;&lt;p&gt;McHutchison reported relationships with Abbott, Anadys, Biolex, Gilead, National Genetics Institute, Pharmasset, Pfizer, United Therapeutics, GlaxoSmithKline, Globimmune, Human Genome Sciences, Idera, Intarcia, Medtronic, Novartis, Roche, Schering-Plough, Vertex, Virochem, and Osiris. Some co-authors were employees of Vertex.&lt;/p&gt;&lt;p&gt;Marcellin reported relationships with Roche, Schering-Plough, Gilead, Bristol-Myers Squibb, GlaxoSmithKline, Wyeth, and Indenix. Some co-authors were employees of Tibotec.&lt;/p&gt;&lt;p&gt;Friedman reported relationships with Exalenz, sanofi-aventis, Axcan, Angion, Intercept, 7TM, Stromedix, and Celera.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_454"
                     title="Livers Under Wrap: AASLD 2005"
                     score="-0.005"
                     href="