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Alan Franciscus

Editor-in-Chief

HCV Advocate



Monday, March 16, 2015

HCV in Japan, by Alan Franciscus, Editor-in-Chief

Of all the industrialized countries of the world, Japan has the highest rate of hepatitis C (HCV).  It also has one of the oldest and most varied histories of hepatitis C in the world among the industrialized modern nations.  Approximately 1.5 to 2 million Japanese are infected with hepatitis C.  Approximately 70% of the Japanese population infected with hepatitis C has HCV genotype 1b, and 30% are infected with genotype 2a/b.

The History of HCV in Japan
Modern medicine and public health came early to Japan in the late 1800’s.  In the early 1900’s, the discovery of the hypodermic needle and a drug to treat schistosomiasis would transmit hepatitis C throughout Japan.

Schistosomiasis
Schistosomiasis is a disease caused by a worm that lives in water snails.  When people wade in water to work on agriculture the worm enters the human body and lays eggs.  The eggs hatch and travel to the liver.   Schistosomiasis causes damage to the liver, the gastrointestinal system, kidneys, and genitals.  It can, over time, cause death.  In some parts of the world, it is considered as deadly as malaria.  The first treatment developed to treat schistosomiasis consisted of multiple intravenous injections of antimony sodium tartrate. By the 1970’s there were approximately 10 million intravenous injections given to people in Japan.  The same type of eradication program was conducted in Egypt, and a similar epidemic of HCV is seen in Egypt.  As in Egypt, treatment of schistosomiasis was the beginning of the HCV epidemic in Japan. The injections were given with used or unsterile hypodermic needles.

Methamphetamine
Nagai Nagyoshi discovered methamphetamine in 1893.  Dr. Akira was able to synthesize it into crystalline meth in 1919.  Widespread use of methamphetamine use did not begin until World War l when it was used as an injectable treatment for asthma.  The large scale use came later during World War II when it was prescribed as an oral and injectable stimulant for tired soldiers, pilots, and ammunition workers during the war.  After the war methamphetamine was prescribed for general post-war trauma.  In 1949, Japan banned the manufacture of methamphetamine, but illegal methamphetamine use continued as did the hepatitis C epidemic.

Modern Japan and Hepatitis C
Hepatitis C and its complications are the leading cause of liver cancer in Japan.  Japan has the highest rates of liver cancer in industrialized countries.  HCV is the 4th leading cause of death among Japanese men and the 5th leading cause of mortality among Japanese women.
Japan has a multi-layered healthcare system.  Many people can get healthcare insurance through their employer or the national healthcare system.  The government system covers about 70%, and the patient covers the remaining 30%.

Interferon-free Therapies 
The first interferon and ribavirin free therapy that was approved to treat hepatitis C is the combination of Daklinza (daclatasvir) and Sunvepra (asunaprevir).  In a clinical trial of Japanese patients with genotype 1b patients treated with the combination of Daklinza plus Sunvepra the cure rate was 84.7%.

Gilead has submitted a New Drug Application to Japan’s Pharmaceutical and Medical Devices Agency for sofosbuvir.  Sofosbuvir plus ribavirin for a treatment duration of 12 weeks to treat 153 HCV genotype 2a patients achieved a cure rate of 97%.  The study was conducted in Japan
Gilead is conducting a phase 3 study of sofosbuvir plus ledipasvir to treat genotype 1 in Japan. 

Source:
http://japanfocus.org/-Vivian-Blaxell/4112

http://hcvadvocate.org/news/newsLetter/2015/advocate0315_mid.html#1

HCV Advocate Weekly Special Topic: HCV Treatment Page


HCV Treatment Page

Check out our revised hepatitis C treatment page for the latest information about the current standard of care to treat hepatitis C, side effects and how to manage those same side effects.

Why we need a petition to increase access to novel therapies

The Alliance for the Adoption of Innovations in Medicine (Aimed Alliance) believes Americans are better served through policies that define the value of new therapies in patient terms, not upfront costs. This means assessing novel therapies on the basis of improved longevity, productivity, and quality of life where the payoff can be substantial.

Given that restricting access harms patients, 15 states and the District of Columbia are taking action, including Delaware, Maryland, and Louisiana, which passed laws capping co-pays on specialty medicines.  Yet, if the real value of novel therapies is to be realized, we need more patient protections at the state and federal levels.  Instead of a petition to impose more cost containment policies, now is the time for a petition to increase patient access to novel therapies through legislative and regulatory remedies.

Read more...

Thursday, March 12, 2015

Hepatitis C a focus at CROI

New interferon-free treatment can cure nearly 100 percent of HIV-positive people coinfected with hepatitis C virus, researchers reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections in Seattle. But another study showed that delaying treatment results in a higher risk of liver-related complications and death even after being cured.

Two studies presented at the conference showed that HIV/HCV coinfected people can expect the same high cure rates as HIV-negative people using recently or soon-to-be approved antivirals.

Susanna Naggie from Duke Clinical Research Institute presented results from ION-4, a trial evaluating Gilead Science's HCV polymerase inhibitor sofosbuvir and NS5A inhibitor ledipasvir – the drugs in the Harvoni coformulation approved last October. The study enrolled 335 coinfected participants, mostly with HCV genotype 1 (the most common type in the U.S.).

Read more...

Australia: Calls for clean needles in West Australian prisons as one in ten inmates test positive for Hepatitis C

BRENDAN TREMBATH: Tests reveal that one in ten inmates in the Western Australia prison system have the infectious disease Hepatitis C.

But a support group says efforts to reduce its prevalence are doomed to fail unless prisoners are given access to clean needles.

Hepatitis WA has renewed calls for the State Government to introduce a needle exchange program.

Read more and listen to the podcast here....

Bristol-Myers Squibb Announces Acceptance of New Drug Application for Investigational Daclatasvir for FDA Review for the Treatment of Hepatitis C Genotype 3

The NDA contains data to support approval for daclatasvir in combination with sofosbuvir; would be the first 12-week regimen specifically for the treatment of hepatitis C genotype 3
 
The application is based on a Phase III clinical trial which tested a 12-week, ribavirin-free regimen and resulted in sustained virologic response (SVR12) in 90% of treatment-naïve and 86% of treatment-experienced genotype 3 HCV patients

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that the resubmitted new drug application (NDA) for daclatasvir, an investigational NS5A replication complex inhibitor, has been accepted for review by the U.S. Food and Drug Administration (FDA) for use in combination with sofosbuvir for the treatment of chronic hepatitis C (HCV) genotype 3. The original NDA has been amended to include data from the Phase III ALLY-3 trial, which showed high cure rates for the combination, with sustained virologic response 12 weeks after treatment (SVR12) in 90% of treatment-naïve and 86% of treatment-experienced genotype 3 HCV patients. SVR12 rates were higher (96%) in non-cirrhotic genotype 3 patients, regardless of treatment history. The FDA will now review the submission within a six-month timeframe.

“The daclatasvir-based NDA seeks to address a high-unmet patient need that still exists despite recent hepatitis C treatment advances. Approximately 9-12% of HCV patients in the U.S. have genotype 3. That’s thousands of individuals in the U.S. who historically have had limited treatment options requiring at least 24 weeks of treatment,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “We also are continuing clinical trials to determine the potential of daclatasvir-based regimens in treating a range of other high unmet-need patients, including those coinfected with HIV, HCV patients with decompensated cirrhosis, and HCV recurrence in post-transplant patients.”

Genotype 3 is estimated to affect 54.3 million people worldwide, and is the second most common hepatitis C genotype after genotype 1 (83.4 million). The more aggressive nature of genotype 3 lies in the damage it causes to the liver, as it is associated with progressive disease, increased rates of steatosis and a disproportionately increased risk of hepatocellular carcinoma.

In the ALLY-3 study, the daclatasvir and sofosbuvir combination regimen was well tolerated, with no deaths, treatment-related serious adverse events, or discontinuations due to adverse events. The most frequent side effects (≥5%) were headache (19.7%), fatigue (19.1%), nausea (11.8%), diarrhea (8.6%), insomnia (5.9%), abdominal pain and arthralgia (both 5.3%). Additionally, there were 17 (11.2%) treatment failures, with 16 relapses post-treatment and 1 rebound at the end of treatment. There were no viral breakthroughs in this ribavirin-free regimen.
 
About ALLY-3: Study Design
This Phase III open-label clinical trial enrolled 152 genotype 3 HCV patients; 101 treatment-naïve patients and 51 treatment-experienced patients in 2 cohorts each received daclatasvir 60 mg and sofosbuvir 400 mg once daily for 12 weeks, with 24 weeks of follow-up. The primary endpoint was SVR12 rates, defined as HCV RNA < LLOQ target detected or not detected at follow-up week 12 in treatment-naïve and treatment-experienced patients.

Read complete press release here
 

Combo Hepatitis C Genotype 3 Tx To Be Reviewed By FDA

Bristol-Myers Squibb announced that the Food and Drug Administration (FDA) has accepted for review the resubmitted New Drug Application (NDA) of daclatasvir in combination with sofosbuvir for the treatment of chronic hepatitis C (HCV) genotype 3.

The initial NDA now includes data from the ALLY-3 trial (n=152), a Phase 3 open-label study in which patients received daclatasvir 60mg + sofosbuvir 400mg once daily for 12 weeks with 24 weeks of follow-up. The study demonstrated high cure rates for the combination therapy with sustained virologic response 12 weeks after treatment (SVR12) seen in 90% of treatment-naive genotype 3 HCV patients, and in 86% of treatment-experienced patients. SVR12 rates were seen in 96% of non-cirrhotic genotype 3 patients, regardless of treatment history.

Read more...