Hepatitis C Treatment/Getting Ready

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Hepatitis C Treatment/Getting Ready

Getting ready for treatment ?Before Starting Therapy your doctor mayrequest the following:1- Eye exam

Click: Hepatitis C Treatment Eye/Retinal & SJS Syndrome Side Effects

2- Electrocardiogram(EKG) if you are over 50 years of age ( Iwas 45 when I treated and my physicianordered one, I had no heart problems priorto treating still I had an EKG)3- For women..pregnancytest REBETOL CAPSULES ANDORAL SOLUTION MAY CAUSE BIRTH DEFECTS AND/ORDEATH OF THE EXPOSED FETUS. EXTREME CAREMUST BE TAKEN TO AVOID PREGNANCY IN FEMALEPATIENTS AND IN FEMALE PARTNERS OF MALEPATIENTS. 4- For your own benefit see your dentistbefore starting treatment and if you needany work done you may want to get it donebefore hand.

5- Your doctor will be doing baseline bloodwork before treatment and will continueduring treatment :PCR should be standard procedure atbaseline , 4 weeks, 12 weeks, 24 weeks, 36weeks, 48 weeks, (f/u) follow up at 4weeks, 12 weeks, 24 weeks and one year.

What You Need to Know Regarding TherapyThere are a number of things you and yourdoctor need to know about your situationbefore you decide to begin therapy and atvarious stages of treatment once it hasbegun. Most of this information can only begained through testing.Before Starting TherapyBefore therapy begins, you will need to havethe following tests, and discuss theseaspects of your medical history. viral genotypeviral loadliver biopsy grade (inflammation/necrosis) andstage (fibrosis) Not All Doctors Recommend A LiverBiopsy Before Treatment; ALTERNATIVE TO BIOPSY STILL NEED A BIOPSY ?

hemoglobin levelwhite blood cell count with neutrophil countplatelet countcryoglobulin levelthyroid stimulating hormone(TSH) level to check thyroid statuselectrocardiogram(EKG) if you are over 50 years

of agepresence or absence of other liver diseases (forexample, hepatitis B, alcoholic liverdisease, etc.), autoimmune diseases,heart or kidney disease, seizuredisorder, diabetes, and/or severe lungdiseasepresence or history of any psychiatric disorder,especially depression or suicidalthoughts; psychiatric consultation maybe required if one of these is presentpregnancy or ability to become pregnant and theuse of appropriate means to preventpregnancy

During TherapyDuring therapy, the following tests need tobe done.complete blood count(CBC) and differential cell count (neutrophils)at 2, 4, 8, and 12 weeks, and then every4 to 8 weeks until therapy is completedALTlevels are usually checked at the sametime points as your

CBCTSH(thyroid stimulating hormone) at 12, 24,and 48 weeksa standardized test for depression (forexample, Beck's Inventory or theHospital Anxiety/Depression Index) aswell as a clinical evaluation fordepression at the time of each visit toscreen for the development ofpsychological problems

You must eliminate all alcohol andstrive to take more than 80% of yourprescribed interferon and ribavirin dosesmore than 80% of the time in order to havethe best chance of achieving a durableresponse.

Please Read this Update about the 80/80rule :

Adherence to HCV therapy is one of the most important predictors of successful HCV treatment. While there are well defined and established guidelines for other disease states such as HIV, hypertension and other diseases, it is less clear when it comes to adherence for HCV therapy. There is an established threshold of 80% for HIV, which means that if a patient does not take 80% of their medications, 80% of the time, the chance of a successful treatment outcome is greatly diminished. There have been retrospective (analyzing data from previous trials) studies on hepatitis C treatment adherence that have been able to establish the 80/80/80 rule. This means that someone taking hepatitis C medications is less likely to have a successful treatment outcome if they do not take 80% of interferon and 80% of ribavirin for 80% of the time. However, the 80/80/80 rule is controversial because it has not been studied in well designed prospective clinical trials. Another concern is that the 80/80/80 rule may be sending the wrong message about treatment adherence since it sets a lower threshold for taking medications rather than encouraging people to take 100% of the medications, 100% of the time or as close to 100% as possible – especially during the first twelve weeks of therapy.

Currently, pegylated interferon and ribavirin do not become HCV resistant so the question of adherence is only important right now with respect to treatment outcomes. However, questions of adherence will become even more important in the future with the development of anti-viral therapies such as HCV protease and helicase inhibitors that will have the potential to mutate and become HCV resistant. We do know that it is important to take as much of the prescribed medications as possible, but this can be difficult considering the moderate to severe physical and psychological side effects of HCV therapy.

There are a number of predictors of treatment response to HCV therapy that are well-recognized as important and this fact sheet will discuss the importance of adherence and well known strategies for helping people achieve a successful treatment outcome. It is also important to remember that not everyone will have a successful treatment outcome even with 100% adherence to HCV therapy. .Continue reading.......... .http://www.hcvadvocate.org/hepatitis/factsheets_pdf/

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HELP/SIDE EFFECTS

TREATMENT STORIES

FIRST SHOT.

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Investigational drugs for hepatitis C

Take home message: In coming years, we can expect that triple therapy becomes a standard medication, and treatment without interferon and/or ribavirin becomes a new studied therapeutic scenario.

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Also SeeTelaprevir or Boceprevir

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DANES SWING A MIGHTY SWORD AGAINST HCV

by LairdA recent article published in Science Expressadded another drug as a candidate for treatment against hepatitis C Virus (HCV)that has shown very exciting possibilities.Clinical trials demonstrate that it is indeedwell tolerated, which may slightly differentiateit from protease and polymerase inhibitors currently in the pipeline as the next addition to the success of treatment.Telaprevir and Boceprevir, when combined with standard therapy, increase the SVR rates in former non-responders with genotype 1 currentlyare producing increased rates of sustainedviral response (SVR) in former nonresponders with genotype 1, raising SVR(and chances of a cure) from 15% to around70%.There are some issues of drug resistancethat develop when some of these proteaseand polymerase inhibitors are used..Some side effects presently end the treatmentfor about 14% of participants. Early

reportingsuggests that this may not be so with thisrecently announced drug.The compound in question is calledSPC3649.The only side effect noted so far isa cholesterol lowering effect. It has produceda 350-fold reduction in HCV levels lasting for two months following 12 weeks of treatment.There was an additional advantagediscovered, as the drug appears to reset theimmune system in non-responders. Sincethere is a genetic disposition involved, somepeople have their immune system shut downrather than fight off the virus when they startinterferon.

It appears that this new drug“actually reset a number of interferon respondinggenes… that were deregulated atthe onset of treatment,†according to SantarisPharma scientist Henrik Orum. “These genesare normalized… suggesting that the gene innon responders could be reset… [to responder levels].â€These studies show no evidence of viral escape, indicating that there will be fewer cases of relapse and non-responders. Viral “escape†or rebound refers to HCV genetic mutation, since the virus has a knack of transforming itself to escape treatment.Incidentally, this response could be followed by a jump of ALT during treatment,which might indicate viral breakthrough. This happens with interferon treatment and still happens with the use of the new complementary drugs nearing development in10 to 15% of cases.This is a good reason to check your ALT regularly during treatment.They may be able to alter

approaches atthis point or consider treatment termination.

The target of the SPC3649, microRNA122,that is required for HCV replication.All of the six genotypes and over fifty subtypes of HCV are ‘addicted’ to microRNA122.

The compound likely binds to it making it unavailable to HCV.

Since microRNA122is universal in many living organisms it is possible that the drug will work for everyone. “This paper adds to the growing body of evidence,†says Orum,“that the inhibitor platform has the potentialto transform the field of RNA targeted therapeutics making specific silencing of RNA targets involved in disease a reality inhuman medicine in the longer run.â€Other recent developments with this technologymay have significant impacts on treatments for HIV, inflammatory disease and even cancer.It demonstrates a real potential for HCV treatment in a cocktail with the other inhibitors without the need for interferon. In the writer’s view announcements like this are likely to be counter productive in BC.It is the practice for the current government to limit access to interferon treatment for arbitrary and contrived reasons.Present standards for qualifying for treatment require abnormally high

ALT for three months when we all know that it is possible to die of cirrhosis without any real change to ALT levels.A study by Dr Rob Myers in Calgary demonstrated that forecasts by epidemiologists for hepatitis mortalities were too low, with four time increases in hospital related liver visits;75% of cases are under reported.Dr Myer's paper came with the potentmetaphor likening the disease to a sleeping giant awaking. Still it is likely that groggy policies will continue with the distorted thinking of BC governance rationalizing thatt here are more effective treatments on the way.People will continue to fall into the abyss of brain fog and other costly symptomsas long as treatment is denied.Also, the people who suffer increased side effects from interferon such as anemia will continue to be denied erythropoietin and subsequently have their hopes dashed as they are denied complementary medicine.

J & F: This is socialized medicine, this is what the US may be facing.After all, if the white blood cell count goes down we know the treatment is working, right? Dr Myer’s sleeping giant still lies in a fitful sleep.http://www.hepcbc.ca/bulletin/2010/2010-01.pdf

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HCV PIPELINE

HCV Pipeline: It’s not surprising that the most important HCV-related news stories in 2009 involved the medications being developed to treat hepatitis C. The two drugs that are furthest along in development are the HCV protease inhibitors telaprevir and boceprevir tested in studies with the combination of pegylated interferon plus ribavirin. Both drugs will finish their development cycle in 2010 and the phase III data is expected to be sent to the Food and Drug Administration (FDA) for marketing approval in 2010-2011. It is possible that the FDA may approve the drugs by 2011 – that is if there are no glitches in the data and if the FDA doesn’t have any important safety or other concerns that are not addressed in the clinical studies.

• Telaprevir (with pegylated interferon and ribavirin): Seems to be the winner on the basis of clinical results and outcomes. Genotype 1 treatment-naïve: In 2009 data from various clinical trials of telaprevir, pegylated interferon plus ribavirin (phase II) found that 69% of genotype 1 treatment-naïve patients treated for 24 weeks achieved an SVR. Re-treatment of people who did not achieve an SVR with a previous course of pegylated interferon plus ribavirin for 48 weeks resulted in SVR rates between 38% and 76% (depending of type of prior non-SVR). The most prominent side effect was skin rash. Another study evaluated the current dosing schedule of thrice daily (current phase III studies) and compared it to a twice daily dosing schedule (with the same daily drug exposure). The twice-a-day dose was found to be as effective as the thrice daily dose. The implications of the results are not completely clear at this time

since all the previous studies and the current phase III studies of telaprevir are using the thrice daily dose..

• Boceprevir (with pegylated interferon and ribavirin): Close on the heels of telaprevir in clinical development. The phase III studies are fully enrolled and they are expected to be completed in 2010. Merck/Schering is expected to apply to the FDA in 2011. Treatment-naïve HCV genotype 1 patients treated for 48 weeks with a combination of boceprevir, pegylated interferon plus ribavirin achieved an SVR of 75%. A small 48 week re-treatment study of boceprevir and pegylated interferon plus ribavirin in people who did not achieve an SVR resulted in an SVR of 55%. The most worrisome side effect of boceprevir is anemia, which is already a problem in ribavirin containing regimes.

• INFORM-1: This study is the first combination HCV therapy of an HCV protease inhibitor (RG7227) and an HCV polymerase inhibitor (RG7128) without interferon and ribavirin. Very early data is quite encouraging with dramatic drops in HCV RNA (viral load). Unfortunately, the 900 mg dose was eliminated from the study due to adverse events so it is unclear what this means for future studies of the combination therapy.

• Albuferon (Zalbin): Human Genome Science’s (HGS) long lasting interferon (dosed every two weeks) tested in combination with ribavirin completed phase III studies and was deemed to be non-inferior to Pegasys (once-a-week dosing) plus ribavirin. Late in 2009, HGS submitted the data to the FDA for marketing approval. Approval is expected in 2010-2011. How this newer long-acting medication will change the landscape of HCV treatment is unclear.

Alan Franciscus, Editor-in-Chief

2010 UpdatesAlan Franciscus, Editor-in-ChiefPart OneThe American Association for the Study of Liver Diseases (ASSLD) conference was recently held in Boston, MA. As expected the majority of information about HCV was from studies on the new drugs being developed to treat hepatitis C. That’s the good news about the conference. The not so good news about the conference is that the information about HCV epidemiology, disease progression and disease management was minimal, which is unfortunate (to say the least) because of all the unanswered questions about these important issues. Having said this, the news about all of the new therapies to treat hepatitis C is very exciting and inspiring especially since we are moving closer to the eventual approval of drugs that will improve the treatment response rates.

It is, however, important to keep in mind that most of the studies reviewed in this report include only a small number of participants and the period of time the drugs are being taken by people is short. Larger clinical trials with a diverse HCV population using a new drug over a longer period of time will give a much better picture of the safety, tolerability and efficacy of a study drug.INFORM-1This is the first clinical trial of the combination of an HCV polymerase inhibitor, RG7128, and an HCV protease inhibitor, RG7227. What is noteworthy is the absence of interferon and ribavirin. The theory behind this clinical trial is that by combining two different types of direct HCV antiviral medications there is a different mechanism of action to attack the virus at different parts of the replication process to help to prevent the virus from becoming resistant to either medication.

Also of note is that the drugs are eliminated differently from the body—one from the kidneys and one from the liver. Another compelling reason for hoping this combination will work is that both are oral medications that only have to be taken twice a day—which will make adherence much easier compared to taking a shot of interferon, multiple doses of ribavirin and possibly 3 daily doses of an HCV direct antiviral a day.All patients in this study were HCV genotype 1 patients who did not have cirrhosis. Treatment relapsers, partial responders and null responders as well as treatment-naïve patients were included in the trial.Part 1In April 2009 the results from part 1 of the phase I study were released. In part 1 the combination dosing for 14 days produced a median reduction of HCV RNA of -4.8 to -5.2 log10 IU/ml in the highest doses; all doses of the combination produced HCV RNA reductions (less than 40 IU/mL) in 63%

of the trial participants The drugs were well-tolerated over the 14-day dosing period with no serious treatment-related adverse events, dose reductions or discontinuationsPart 2The objective of the second part of the study was to assess the safety and tolerability of a combination of the two drugs for up to 13 days.All of the study medications were dosed at BID (twice a day) and in each group two patients received a placebo (sugar pill). A total of 24 patients were randomized to one of three treatment arms; the RNA decline is listed after the dosing regimen below:8 patients who were treatment failure but NOT null-responders received 1000 mg RG7128 plus 600 mg RG7227-4.0 log10 IU/ml (range -6.0 to -2.5); HCV RNA < ml =" 1" ml =" 2" svr="85%" svr="81%" svr=" 82.5%" svr="82.1%" arms =" 2250">

The sustained virological response rates between the two groups (total treatment duration) was not broken down so the results below are listed by type of response: 1. Prior null responders (patients who had a viral load reduction <

1 log10 at week 4 or <> 2 log10 at week 12, but who had detectable HCV RNA at week 24. A total of 29 patients of whom 16 (55%) achieved an SVR.3. Prior relapsers (patients who had an undetectable viral load during treatment, but had detectable viral load after treatment ended. A total of 29 patients of whom 26 (90%) achieved an SVR.4. Prior viral breakthrough (patients who had undetectable viral load during treatment, but detectable viral load before the end of treatment. A total of 8 patients of whom 6 (75%) achieved an SVR.*The SVR rates are combined for both treatment durations by type of non-response, but it was noted that the optimal treatment duration is 48 weeks.According to a company press release the side effect profile was similar to what has been seen in previous telaprevir studies.Comments:This important but small study is encouraging for improving the SVR rates in people who

have been previously treated with pegylated interferon plus ribavirin therapy. The larger phase III studies of people who did not achieve an SVR with a previous course of pegylated interferon plus ribavirin will give us a much better picture of the future of retreatment in the HCV population that is in the most need of treatment options.BOCEPREVIRThe SPRINT-1 was a phase II study of HCV genotype 1 treatment-naïve patients. In the current retrospective study, data from patients from the original study who achieved less than a 1 log10 drop in HCV RNA viral load (called null-responders in this analysis) after 4 weeks of PegIntron plus ribavirin (lead-in phase) was analyzed. All the patients received either 24 or 44 weeks of additional treatment with boceprevir, PegIntron and ribavirin. A total of 206 patient records were analyzed. In

both groups of null-responders the SVR rate was 38% (16 out of 50 patients). In the group that was treated for 28 weeks the SVR rate was 25% (7 out of 28 patients) and 55% (12 out of 22 patients) in the group that received 48 weeks of therapy.Another analysis of the SPRINT-1 clinical trial noted that people who achieved a rapid virological response after treatment with boceprevir, PegIntron and ribavirin were able to achieve an SVR rate of 82% (54 out of 66 patients) in the 28 week treatment arm. In the patients who did not achieve an RVR but who were HCV RNA negative by week 16 and were treated for 48 weeks there was a 79% (15 out of 19 patients) SVR. These results support the rationale for response-guided therapy.Comments:While these results are impressive a couple of caveats need to be made: the findings are from an analysis of previous data which can prove to

be a slippery slope, and there were small patient numbers as well. The phase III studies of boceprevir will yield much more accurate information about response-guided therapy.In part 2 of AASLD conference coverage I will discuss the results from more than a dozen studies of the new agents that are being developed to treat hepatitis C.Part Two/ Jan 2010In the article “AASLD 2009: Part 1†(above) in last month’s HCV Advocate newsletter, I discussed the top performers in the new class of HCV direct antivirals—telaprevir, boceprevir and the INFORM-1 combination trial. In “AASLD 2009: Part 2†I will discuss some of the many new drugs that are being developed to treat hepatitis C. The drugs listed below are in very early development (Phase I and Phase II) so the data presented here will be very brief.HCV PROTEASE INHIBITORSPHX1766: In a study of healthy volunteers and HCV

genotype 1 patients who were given PHX1766 it was found that the average maximal HCV RNA decline after 6 days was -1.2 log10 in the 400mg BID group and -1.8 log10 in the 800mg BID group. PHX1766 was generally well-tolerated. One serious adverse event was reported, but the investigators believed that it was unrelated to the study drug.MK-7009: Updated information about the ongoing trial was presented. The proportion of subjects who achieved RVR in the MK-7009-containing arms ranged from 69% to 82%, vs. 6% in the placebo group, and the percentage of patients who achieved an EVR ranged from 76 to 89% compared to 60% in the placebo group. No serious adverse events resulted in treatment discontinuation.TMC435: A study of prior non-responders and treatment-experienced patients found that at day 28, all four patients who completed treatment achieved HCV RNA >

Three of those four patients had HCV RNA below the lower limit of detection (> POLYMERASE INHIBITORS Narlaprevir: Two studies of narlaprevir were presented at AASLD. In the first study, participants were given narlaprevir (twice daily or thrice daily; with and without ritonavir) and PegIntron for 2 weeks followed by PegIntron plus ribavirin for 24 or 48 weeks. A total of 41 (20 treatment-naïve; 21 treatment-experienced) HCV genotype 1 patients were treated.

The sustained virological response rates were 81% (13 of 16 patients) in the treatment-naïve group; 17% (1 of 6 patients) in the prior non-responder group; and 50% (5 out of 10 patients) in the group who were prior relapsers. The side effect profile was consistent with side effects seen with pegylated interferon plus ribavirin therapy.

The results of this study showing potent antiviral activity of narlaprevir when combined with ritonavir prompted the design of the second study combining a once-a-day dose of narlaprevir with ritonavir. In the second study, a total of 111 HCV genotype 1 treatment-naïve patients were randomized into 6 groups with different doses of narlaprevir, ritonavir, and PegIntron plus ribavirin. It was found that the 200 mg/ 400 mg narlaprevir/ritonavir once-a-day groups achieved undetectable HCV-RNA levels at week 4 in 58-87% of patients and at week 12 in 84-87% of patients. Narlaprevir/ritonavir was found to be generally safe and well-tolerated.

There was an increased frequency of anemia compared to the group that did not receive narlaprevir/ritonavir. A total of 20 patients discontinued treatment due to side effects—12 to 16% in the narlaprevir arms vs. 39% in the PegIntron plus ribavirin control group.

MK-3281: Twenty-two HCV genotype 1 a/b and genotype 3 male treatment-naïve patients and treatment-experienced patients were treated with MK-3281 monotherapy for 7 days. There was up to a 3.75 log10 (-1.28 to – 3.75) decrease in HCV RNA.

The best antiviral response was seen in HCV genotype 1b patients (-3.75 log10). The drug was generally safe and well-tolerated.

The most common side effects reported were headache, migraine, dizziness, tiredness, loss of libido, and abdominal pain.

PSI-7851: Results from a multiple dose (50mg, 100mg, 200mg or 400mg) study of 40 treatment-naive HCV genotype 1 patients who were treated with PSI-7851 mono therapy for 3 days were presented. A dose-dependent HCV RNA decline of up to -1.95 log10 IU/mL was observed. The drug was generally well-tolerated for the short period of time it was given. Additional studies of PSI-7851 in combination with pegylated interferon plus ribavirin are being planned.

ABT-333: 41.7% (10 out of 24 patients) who were treated for 28 days with ABT-333 plus pegylated interferon and ribavirin after 28 days of treatment had less than 25 IU/mL HCV RNA (viral load) compared to none out of 6 patients in the placebo, pegylated interferon/ribavirin arm (without ABT-333) for 28 days. The side effects were reported to be mild in severity (85%) with 63% believed to be from pegylated interferon/ribavirin. There were no serious adverse events or discontinuations due to adverse events. IDX184: A three-day, phase I proof-of-concept study evaluating the safety and antiviral activity of IDX184 (monotherapy) enrolled 41 treatment-naive HCV genotype 1-infected patients into four dosing groups (25 mg, 50 mg, 75 mg and 100 mg). Mean viral load decreases ranged from 0.47 log10 in the 25 mg group to 0.74 log10 in the 100 mg group after three days of treatment. IDX184 was well-tolerated in this study with no serious adverse events reported and no discontinuations from the study. Idenix announced that it has begun a phase II study of IDX184 in combination with pegylated interferon and ribavirin.

BI 207127: In a small trial of 60 HCV genotype 1 treatment-naïve patients, BI 207127 was found to be a potent inhibitor of viral replication in monotherapy, causing a sharp decline of viral load at 800 mg every 8 hours in the first 24 hours (5/9 patients with > 4 log10 reduction at Day 5, and no viral load breakthroughs). BI 207127 was generally safe and well-tolerated in this study; the only drug-related severe adverse event, a moderate erythema (red skin/rash), was managed effectively. Two other cases of mild transient rash occurred, but it did not require BI 207127 dose reduction or discontinuation. A 4-week combination study with doses of BI 207127 up to 800 mg thrice daily in combination with pegylated interferon and ribavirin will be completed in the 4th quarter of 2009.THERAPEUTIC VACCINEGI-5005: There was a report from an ongoing Phase 2b study to compare GI-5005 plus pegylated interferon and ribavirin versus pegylated interferon plus ribavirin alone (without GI-5005) in 140 HCV genotype 1 patients who were either treatment-naïve or prior non-responders produced modest results. On a modified intent-to-treat basis (patients having received at least one dose of combination therapy), treatment-naïve patients receiving GI-5005 plus Peg/ribavirin as a triple therapy had an end-of-treatment complete response rate (HCV RNA <> Also See

Telaprevir or Boceprevir Deciding Not To Treat HCV/What Next?

http://Hepatitis Cnewdrugs.blogspot.com/2010/02/hepatitis-c-treatmentgetting-ready.html