From the end of 2015 to 2016, mass infections of hepatitis C occurred at three hospitals. Before these incidents, chronic hepatitis C had not been a significant disease in Korea. Around the same time, new medicines with sharply improved cure rates were released, but they remained largely unknown because of high prices and the low attack rate of hepatitis C in Korea.

However, the mass infection increased the awareness of the importance of prevention and treatment of hepatitis C, as well as issues concerning disposable syringe use. Reflecting the mounting public concern about the disease, the government included, with unusual swiftness, its treatments in the health insurance coverage, and the National Screening Program for the Transitional Ages.

Along with policy changes, the trend of its treatment also rapidly shifted in the clinical field, from interferon-oriented cure to direct acting antivirals (DAA).

It is against this backdrop Korea Biomedical Review talked with the experts in Korea and the United States to hear their views on recent changes in the treatment of Hepatitis C. Following Professor Cheon Dae-won of Hanyang University College of Medicine, KBR met with Professor K. Rajender Reddy in the digestive internal medicine department at Penn Medicine, Hospital of the University of Pennsylvania. Professor Reddy was visiting Korea with an invitation from MSD, and he shared his knowledge about the latest in Hepatitis C medication and MSD’s newly approved Zepatier (active ingredient elbasvir/grazoprevir).

Professor Reddy discusses Hepatitis C medication trends in a recent interview with Korea Biomedical Review.

Question: We have heard you participated in Zepatier Global’s research for the primary clinic of C-EDGE TN research.

Answer: C-EDGE TN was a 12-week clinical trial using Zepatier to treat patients with HCV genotypes 1, 4 and 6. A total of 408 patients with HCV genotypes 1 and 4, the genotypes deemed vaccine-efficacious, and we also had cirrhosis patients among the subjects. The clinical tests were quite successful.

“Sustained Virologic Response (SVR) 12” regarding Hepatitis C refers to the condition when the virus is not detected when measured at 12 weeks after treatment has ended. Overall, the clinical trial results showed an extremely high SVR. At 12 weeks, 95 percent of patients reached SVR12, and those with HCV genotype 1b showed a 99-percent rate. Additionally, genotype 1a patients reached 92 percent, genotype 4 reached 80 percent, and genotype 6 reached 97 percent.

Q: Does the construction of C-EDGE TN have any unique features or differences compared with the existing new Hepatitis C medications?

A: A characteristic of C-EDGE TN was the existence of a delay group. Clinics divide patients into two groups, a test group, and a control group, to prevent ambiguities about treatments’ side effects. The control group was given a placebo for 12 weeks, then administered with a Zepatier treatment.

Research regarding the compound agent Harvoni (active ingredients sofosbuvir/ledipasvir) lacked a control group at the beginning of clinical trials, but the C-EDGE TN clinic had a treatment delay group as the control group. Because the clinic did not compare various treatments one on one, however, we can’t judge which remedy is superior.

Q: What clinical usefulness does Zepatier have over the existing therapies?

A: One unique characteristic is that Zepatier is a medication that can also safely be used on patients with advanced renal diseases, like chronic kidney disease. Most medicines with sofosbuvir are difficult to use in patients with advanced renal diseases, which we are defined here as stage 4 and 5 or dialysis patients. We ran a separate clinic called C-SURFER targeted for these patients to prove Zepatier’s effectiveness. It’s significant that patients who have received kidney transplants now have a safe medication option.

Zepatier showed a 99-percent SVR rate with HVC genotype 1b patients. Another of its strength is its treatment ability at one pill a day.

Q: What’s the factor that caused advanced renal disease patients to show differences regarding HVC medication?

A: Sofosbuvir is an NS5B nucleoside polymerase inhibitor, which gets converted into a metabolite when it enters the body. Chronic kidney disease patients suffer a continual accumulation of metabolites. Because Zepatier gets metabolized in the liver, there’s no risk of accumulation in the kidneys, so renal disease patients experience no metabolism changes.

Q: What are Zepatier and other new HCV medications’ drug-drug interactions (DDI)?

A: Ledipasvir within sofosbuvir/ledipasvir causes proton pump inhibitor (PPI) interaction and is recommended not to be used together. It’s known that if administered together with PPI, ledispavir’s absorption rate is lowered and causes an adverse effect.

Using Zepatier with statins medications requires caution, but there’s no big problem if it’s administered at a lower dosage. Doctors can usually manage HCV drug’s DDIs, but cases of older patients using statins and PPI’s together require extra caution.

Q: Since the investigations after the mass HCV infections in Korea, people have voiced opinions that HCV might have flown in and occurred through transfusions, tattoos, and various other routes. What are your views regarding the causes and pathways of HCV infection?

A: The number of acute HCV patients is rapidly increasing worldwide. In the United States, pneumonia and the extensive use of Meta Kit intravenous injections are seen as the primary pathway for infections. Intravenous injections are considered to be the main route for infections in countries that have a lower average prevalence of infections. Countries with a higher prevalence have a huge variety of infection routes. Infections within hospitals are most common, mostly caused by syringe reuse and rectoscope tests. One can also be exposed to Hepatitis C through the use of unsanitized equipment at barber shops and the like.

Q: What does the recent continuous development of HCV medications signify?

A: The emergence of diverse treatment options itself is significant. The improved quality of treatment means HCV treatment is not difficult. Our final task now is to eradicate Hepatitis C. I believe eradication by 2030 is possible. The World Health Organization, countries, foundations and many others are making efforts for the cause.

Georgia, Portugal, Australia, Iceland, and other nations are success stories of HCV eradication. Australia has had patients receive HCV treatment regardless of treatments’ success rates, and Iceland and Georgia have also established excellent HCV-related programs. Portugal has about 10,000 HCV patients but anticipates eradication soon. Perhaps it’s time Korea talk beyond curing HCV to eradicating it.

Q: Have there been cases of patients developing a tolerance for HCV medication? If so, how can they be treated and managed?

A: Compound agents that can also be used on patients with tolerance will soon make their debuts. We predict genotypic medication or triple therapy will be effective even for patients who develop tolerance. Personally, I believe we should see high cure rates as positive, over focusing on cases of tolerance. Of course, patients who don’t respond to medicine will require additional treatment, but it shows hope that a vast majority of patients are completely cured under treatment. The upcoming genotypic medications and triple therapy methods will be used not as a primary treatment but for cases where primary treatments fail.

Q: While the increase of HCV treatment options is positive, some have said it causes confusion. Personally, what methods do you use to prescribe treatment?

A: Efficacy and safety are important. Personally, I prioritize efficacy and examine whether the treatment is amply safe. I don’t prefer prescribing ribavirin because it requires several types of monitoring and blood tests.

As a doctor, eradicating Hepatitis C is the top priority. Therefore every patient must be prescribed the medication that shows the best effects, and I consider ease of use second to that. That is, if the safety is amply guaranteed, I choose the treatment with greater efficacy even if it’s a little harder to use, and if two treatments have the same efficacy, I choose the one with greater ease of use.

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