HCV TRANSFORMING MANAGEMENT IN EGYPT

HCV: TRANSFORMING MANAGEMENT IN EGYPTDr-MOHAMMED EMAMZagazig university-2014

We're all really excited that for the first time we have curative therapies for hepatitis C which are much more effective than what we had before and much easier to tolerate,

We think the move away from interferon and toward a high probability of success is remarkably encouraging for all of us.... Suddenly, it's true to think that we can cure most patients with hepatitis C,"WHERE WE ARE NOW?

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Sofosbuvir is a game-changer and will allow high cure rates with just 12-week regimens," sofosbuvir holds numerous advantages over current therapy because of its: -Efficacy profile, -Safety, -Tolerability across many different patient populations and HCV genotypes, -Dosing simplicity.

....INDICATIONS AND USAGE :SOVALDI is Indicated for :-Treatment of chronic hepatitis C (CHC) infection as a part of a combination antiviral treatment regimen.

Source: Ruane P, et al. 49th EASL. April 2014: Abstract P1243.Sofosbuvir and Ribavirin in HCV Genotype 4Egyptian Ancestry Trial: Study FeaturesEgyptian Ancestry Genotype 4 Trial: FeaturesDesign: Randomized, open-label, phase 2 study of sofosbuvir + ribavirin in treatment-nave and treatment-experienced patients with HCV GT 4 Setting: single study center in United StatesEntry Criteria - HCV Genotype 4- First generation Egyptian- Treatment nave or treatment experienced- Age 18 or older- Not co-infected with HIV- Patients with compensated cirrhosis allowed Primary End-Points: Efficacy (SVR12) and safetySource: Ruane P, et al. 49th EASL. April 2014: Abstract P1243.Sofosbuvir and Ribavirin in HCV Genotype 4Egyptian Ancestry Trial: Baseline CharacteristicsChronic HCV GT4: Treatment with Sofosbuvir + RibavirinBaseline CharacteristicTreatment NaiveTreatment Experienced12-Week (n=14)24-Week(n=14)12-Week(n=17)24-Week(n=15)Mean Age, y (range)53 (26-69)52 (27-75)54 (32-72)57 (38-68)Male, n %8 (57%)5 (36%)14 (82%)14 (93%)Mean BMI kg/m229.230.928.129.6Cirrhosis, n %3 (21%)3 (21%)4 (24%)4 (27%)IL28B non-CC, n (%)11 (79%)8 (57%)16 (94%)15 (100%)Prior schistosomiasis, n (%)8 (57%)3 (21%)6 (35%)8 (53%)HCV RNA, mean baseline log10 IU/ml5.75.96.26.1Source: Ruane P, et al. 49th EASL. April 2014: Abstract P1243.Sofosbuvir and Ribavirin in HCV Genotype 4Egyptian Ancestry Trial: DesignDrug DosingSofosbuvir: 400 mg once dailyWeight-Based Ribavirin (in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if 75 kg2436Week012SVR12SVR12Sofosbuvir + RBV(n = 28)Sofosbuvir + RBV(n = 32)GT 4 Naveor Experienced Sofosbuvir and Ribavirin in HCV Genotype 4Egyptian Ancestry Trial: ResultsSVR 12 by Regimen Duration and Treatment ExperienceSource: Ruane P, et al. 49th EASL. April 2014: Abstract P1243.Treatment NaiveTreatment Experienced 11/1410/1714/1413/1519Phase III NEUTRINO study: 96% SVR12 rate in patients with genotype4 HCV treated with sofosbuvir plus pegIFN/RBV for 12 weeksCurrent pilot study evaluating sofosbuvir plus RBV in immigrants of full Egyptian ancestry in the US infected with genotype 4 HCV"

HCV FREE WORLD

NO DREAMS WITHOUT PROBLEMS

Guidelines for low and middle income countriesMost of the existing guidelines for the treatment of hepatitis C have been developed by specialist medical organizations and relate to the treatment of persons with different genotypes and living in high-income countries. There are no evidence-based treatment guidelines that focus on persons living in low- and middle-income countries.

.The suggestive objective of these guidelines These guidelines will provide a framework for the development or strengthening of hepatitis C treatment programmers' in low- and middle-income countries(especially in Egypt) according to evidence-based recommendations on screening for HCV infection, and the care and treatment of persons with HCV infection aiming to achieve a mass treatment in our locality

Price of medicines

HCV treatment is expensive. Prices range from US$ 5 000 in Egypt for 48-weeks of PEG/IFN RBV to as much as US$84 000 in the US for a single 12-week course of sofosbuvir.

At these prices, these treatments will remain unaffordable for most persons who need treatment. A concerted effort is needed to reduce the price of HCV medicines.

The experience with HIV, where the price of antiretrovirals was reduced by nearly a hundred fold through the introduction of generic drugs, has shown that the key to achieving low prices for medicines is to use a multipronged approach..key to achieving low prices for medicines :This can include1- Voluntary licensing (where the patent owner licensesthe medicine to generics-producing companies or a patent pool),

2- Tiered pricing (where the manufacturer sets different prices for different countries based on their income level and disease burden),

3- compulsory licensing (where a national government grants a license to companies producing generic drugs or importing the product

4-National governments, international agencies, donors,civil-society organizations, and the pharmaceutical industry will need to work together to help assure that hepatitis C treatment is affordable and accessible for all those who need treatment.

The primary goal of HCV therapy is to cure the infection.

A sustained virological response (SVR) is defined as undetectable HCV RNA 12 weeks (SVR12) or 24 weeks (SVR24) after treatment completion.

The infection is cured in more than 99% of patients who achieve an SVR.

The SVR is generally associated with resolution of liver disease in patients without cirrhosis.

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Patients with cirrhosis remain at risk of life-threatening complications; however hepatic fibrosis may regress and the risk of complications such as hepatic failure and portal hypertension is reduced.

More data is required to ascertain the lifetime residual risk of hepatocellular carcinoma after viral infection has been eradicated.

In addition to pegylated IFN- and ribavirin, three new HCV DAAs licensed in the first half of 2014, for use as part Of combination therapies for HCV infection. 1-Sofosbuvir, a nucleotide analogue inhibitor of HCV RNA-dependent RNA polymerase, has been approved in January 2014. 2-Simeprevir, a second-wave, first generation NS3/4A protease inhibitor approved in May 2014.3-Daclatasvir, an NS5A inhibitor, is likely to be approved in August or September 2014. Other drugs may be approved later in 2014 or in 2015.

Who should be treated?

All treatment-nave and -experienced patients with compensated disease due to HCV should be considered for therapy (Recommendation A1) Treatment should be prioritized for patients with significant fibrosis (METAVIR score F3 to F4)(Recommendation A1) Treatment is justified in patients with moderate fibrosis (METAVIR score F2) (Recommendation A2)

In patients with no or mild disease (METAVIR score F0-F1), the indication for and timing of therapy can be individualized. Patients with decompensated cirrhosis who are on the transplant list should be considered for IFN-free, ideally ribavirin-free therapy

Available drugs (approved by before the end of 2014Pegylated IFN-2a should be used at the dose of 180 g/week,whereas pegylated IFN-2b should be used at the weight-based dose of 1.5 g/kg/week. Ribavirin dose should be 1000 or 1200 mg/ day, based on body weight (