Wednesday, October 6, 2010

Hepatitis C Timeline - First recorded references to hepatitis epidemics, to the 1989 discovery of the hepatitis C virus, ending with the FDA approved treatments used today.

Page updated January 2017

HCV Flashback: Ancient History

2000 B.C.
First recorded references to hepatitis epidemics.

F.O. MacCallum, using human volunteers, differentiates hepatitis A, which is spread by contaminated food and water, from hepatitis B, which is spread by blood.

Baruch Blumberg and Harvey Alter discover Aa, the Australian antigen (later called HBsAg)..

Blumberg, Kazuo Okochi, Alfred Prince, Alberto Vierrucci, and colleagues report that Aa is involved in the development of hepatitis B.

Irving Millman and Blumberg devise a concept and through the Fox Chase Cancer Center receive a patent for using Aa to prepare a hepatitis B vaccine.

D. S. Dane discovers whole hepatitis B virus particles in blood samples examined with the electron microscope.

Laws are passed in the United States requiring testing of donor blood for HBsAg antigen.

Stephen Feinstone and colleagues and Maurice Hilleman and colleagues discover and describe hepatitis A virus

Post-transfusion non-A, non-B hepatitis was first described as hepatitis C

Hepatitis C  A New Virus
Consequently, chronicity of post-transfusion non-A, non-B hepatitis was discovered as a blandly symptomatic disease with elevation of the liver enzyme alanine aminotransferase (ALT) and chronic hepatitis seen on liver biopsy.

The infectious nature of the entity was confirmed when the disease could be conveyed from humans to chimpanzees. The etiologic agent, the hepatitis C virus (HCV), was recognized as a genetic sequence in 1989 by Choo through random polymerase chain reaction (PCR) assays in plasma of chimpanzees chronically infected with non-A, non-B hepatitis, that led to the development of a first-generation HCV antibody test that identified HCV as the basis of majority cases of formerly "diagnosed" non-A, non-B hepatitis.

In 1974, it was first recognized that not all cases of viral hepatitis were hepatitis A or hepatitis B. It proved difficult to identify the infectious agent responsible for these cases of non-A, non-B hepatitis. However, it has recently become clear that many cases of post-transfusion non-A, non-B hepatitis are the result of infection with a new virus, hepatitis C
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Wolf Szmuness and Hilleman and colleagues begin tests of the hepatitis B vaccine.

Mario Rizzetto and John Gerin discover hepatitis D.

Subunit hepatitis B virus vaccine derived from blood serum is developed by Hilleman and colleagues, proved effective and licensed for general use.

The Lancet, Volume 317, Issue 8227, Pages 982 - 984, 2 May 1981

Original Text
L.J. Farrow a, J.S. Stewart a, H. Stern b, R.E. Clifford c, H.G. Smith c, A.J. Zuckerman

Acute and convalescent sera from 368 patients drawn from a 3-year survey of viral hepatitis in West London were tested by radioimmunoassay for evidence of recent infection with hepatitis A or B and, if neither was found, antibody to Epstein-Barr (EB) virus and cytomegalovirus. In 215 patients (58%) there was evidence of hepatitis A, in 98 (27%) hepatitis B, and in 5 both A and B. 2 patients with evidence of recent EB virus infection were excluded, leaving 48 (13%) attributed to non-A, non-B hepatitis. This illness was milder than hepatitis B as judged by duration of jaundice and peak serum bilirubin alanine-aminotransferase levels. The ratio of men to women was 1.4 to 1, but there was an excess of women in their twenties, most of whom were single. Only one had received blood, and none was a drug addict.

Mikhail Balayan describes the hepatitis E virus.

Subunit hepatitis B virus vaccine derived from yeast is developed by William Rutter and colleagues and approved for use.

"In the United States, non-A non-B hepatitis afflicts about 120,000 people a year, 90,000 of whom get the disease through blood transfusion. An estimated 1,000 Americans die each year from non-A non-B hepatitis"

"Dr. Prince said he did not believe the virus his group had found was a retrovirus. He proposes that it be called the ''hepatitis C virus.''The hepatitis in question is now called non-A non-B, signifying that it represents liver disease caused by a virus or viruses other than the two known viruses hepatitis A and hepatitis B. Hole in Screening Process"


November 18, 1984
Scientists of the New York Blood Center have reported the discovery of a new virus they believe may be the major cause of hepatitis transmitted through blood transfusion. The report was the second in two weeks to claim discovery of the probable cause of most cases of post-transfusion hepatitis, a liver disease that affects 90,000 Americans each year. Whether or not the two reports represent the same virus is unknown. If either or both of the research teams that issued reports have found a major cause of this form of the disease, called non-A non-B hepatitis, it may be possible to develop screening tests to eliminate the viruses from blood used for transfusion.....
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Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon.
A preliminary report.Volume 315:1575-1578 December 18, 1986 Number 25

We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement
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Daniel Bradley provides Chiron with non A-non B hepatitis serum from chimpanzees; Michael Houghton and colleagues discover a single virus, publish the genetic sequence of the viral agent, and change the name to hepatitis C.

Blood screening for hepatitis C begins.
January 1990

Hepatitis C test shows promise, pitfalls
An experimental blood test that detects antibodies to hepatitis C in donated blood identities many, but not all, tainted units, two studies indicate. The data suggest that the test, now under consideration by the Food and Drug Administration for routine use in blood banks, will reduce the number of transfusion-associated cases of hepatitis C. But the test's inability to flag all infectious units hints at the presence of an undiscovered causative agent underlying some hepatitis cases, and highlights the difficulties of eliminating the potentially fatal river disease.

FDA Approves Hepatitis C Treatment; Alpha Interferon to Be Used Against Infectious Liver

FDA approves first alfa interferon (Schering’s Intron A) to treat hepatitis C.
By LAWRENCE M. FISHER, Special to The New York Times
Published: February 26, 1991
SAN FRANCISCO, Feb. 25— The Schering-Plough Corporation received Food and Drug Administration approval today to use alpha interferon, one of the earliest drugs produced by biotechnology, for the treatment of hepatitis C. Alpha interferon is the first treatment approved for this sometimes fatal viral infection, which causes chronic liver inflammation and can lead to cirrhosis and liver cancer. which is marked by sustained inflammation of the liver - making them candidates for the drug.

FDA approves first interferon (Schering-Intron A) to treat hepatitis B.

"The committee also suggested that public service announcements be developed to notify people who received blood donations prior to May 20, 1990, to get a test for hepatitis C"

Blood and Hepatitis C; FDA Advises Tracing Recipients When Transfusion Is Tainted

The Washington Post -
Washington, D.C. Author: Sally Squires Date: Dec 7, 1993
The FDA requires the tracing, or look backs, of blood in cases where the blood donor, sometime after the donation, is found to be HIV-positive. Blood is not accepted from anyone who says he has HIV or hepatitis, and it is tested at the time of the donation and discarded if tests reveal the donor has either of the diseases. Sometimes, though, the donor may have contracted one of the diseases but not yet developed the immune system antibodies to fight the viruses, so the blood will pass through the testing undetected. It is blood from those donors that would be traced.The FDA's Blood Products Advisory Committee also recommended unanimously that blood banks begin retrieving and discarding stored plasma and blood products from donors who had recently tested positive for hepatitis C. This would occur even though at the time the blood was drawn the donors tested negative for hepatitis C. The committee also suggested that public service announcements be developed to notify people who received blood donations prior to May 20, 1990, to get a test for hepatitis C.

FDA approves alfa interferon (Roche, now Genentech- Roferon A ) to treat hepatitis C.

FDA approves consensus interferon (Amgennow InterMune-Infergen) to treat hepatitis C.

FDA approves Rebetron (Schering’s Intron A plus ribavirin)for the treatment of hepatitis C.

Approved Peg-Intron (Schering’s pegylated interferon alpha-2b) was the first pegylated interferon FDA approved to treat hepatitis C.

Pegasys Approved
Pegasys (Genentech’s pegylated interferon alpha-2a) was approved to treat hepatitis C

Intron A (interferon) plus Rebetol (ribavirin- available in oral solution) approved for treating pediatric patients with chronic hepatitis C.

Of Interest
Halted - First protease inhibitor
In 2003 the first protease inhibitor to enter clinical trials was Boehringer Ingelheim's ciluprevir (BILN 2061) but clinical development was halted in 2006 because of cardiotoxicity in animals. 

Halted - First nucleoside polymerase
In 2004 the first nucleoside polymerase to enter clinical trials was Idenix Pharmaceuticals and Swiss partner Novartis drug Valopicitabine which was discontinued in 2007 because of modest antiviral efficacy along with significant gastrointestinal side effects. 

HCV Replicated in Test Tube

Mouse Model Scientists made dramatic in roads into understanding the various mechanisms of action of the hepatitis C virus and replicated various HCV genotypes in a test tube.

Drugs in Development In 2007, many new drugs were advanced into development. The leading compound is VX-950 (telaprevir) an HCV protease inhibitor that is being developed by Vertex

Drug Telaprevir in Patients with Genotype 1 Hepatitis C May Cut Treatment Time.

Hepatitis B found in South Korean 500 year old mummy's liver

Diabetes Doubles Liver Cancer Risk For Patients With Advanced Hepatitis C

Direct antiviral medications telaprevir and boceprevir(HCV protease inhibitors) finish enrollment in their clinical trials and expect to complete their trials and file formarketing approval late in 2010.

Roche's 18-minute Elecsys Antibody anti-HCV test would scan for total antibodies in human serum or plasma.The test may be used in the diagnosis of HCV infections in those with symptoms of hepatitis or at risk of hepatitis C which is primarily transmitted through contaminated blood and blood products

In May the first direct-acting antivirals (DAAs) boceprevir and telaprevir received FDA approval.

On May 23, the FDA approved protease inhibitor Incivek-telaprevir for the treatment of HCV genotype 1 patients and on May 13, Vicrelis/boceprevir with the same indication was also approved.

Geographic distribution of genotypes

The geographic distribution of genotypes is a starting point for a rich and harrowing look at how viruses move across the world. For example, one of the ways that hepatitis was spread through Egypt was through a campaign against schistosomiasis along the Nile delta in the 1960s.

(Here is one interesting PDF on that.) It was a well-intentioned and needed public health measure but the needles weren’t sterilized and so as people were treated for the parasite, village by village, the virus made its way around. Egypt currently has the highest rates of HCV in the world. Anti-malaria campaigns in Cameroon had a similar impact.

Also fascinating is the fact that the spread of the virus can be traced across slave trade routes from Africa to Europe. And, as Oliver Pybus, an evolutionary biologist at Oxford University, points out, that fact brings up another central mystery about HCV, which is that the virus has been around for thousands of years, but the most common modes of transmission that we know of are connected to relatively modern inventions (blood transfusions and needles to inject drugs). “What is clear is that this endemic transmission was occurring across the whole of Sub-Saharan Africa and Asia and it doesn’t seem right that it would be maintained by very culturally-defined and location-specific routes of transmission,” Pybus once told me. In other words, as he explained, practices like scarification and tattooing could account for some, but not all, of the spread of HCV in that time and place. Making his insights even more fascinating is the fact that Pybus has managed to use genome sequencing and computer programs to trace the phylogenetic tree of HCV that extends over thousands of years. (Pybus was the CDC’s point person on tracking the origin of swine flu a few years back because of the software and methods he’s invented.)
Continue reading....

How Did HCV Infect Humans?
Then there is the question of how HCV got into humans in the first place. Columbia University virologist Ian Lipkin recently shed some fascinating light on this question when he found a genetic homolog of HCV in dogs. Here’s a tiny bit from me on that and a lot more about it from Carl Zimmer.
Continue reading....

Treatment of chronic hepatitis C genotype 1 with triple therapy comprising telaprevir or boceprevir
INCIVEK® (telaprevir) - Updates label after reports of a ‘small number of fatal skin reactions’
Vertex discloses Hep C drug deaths

2012 - New Antiviral Agents for Hepatitis C
This article describes the direct acting antivirals and host-targeted agents that have recently been approved or have been tested in HCV-infected patients and discusses their two current paths of clinical development: with or without interferon-α.

Bristol-Myers Squibb - BMS-986094 (formerly INX-189) - Discontinued
BMS halts the development of BMS-986094 due to patient death The original patient subsequently died and eight others suffered from heart and kidney toxicity, the company said in a statement released last night. Two of the patients remain hospitalized.
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The Centers for Disease Control and Prevention (CDC) and US Preventive Services Task Force (USPSTF) recommend that all baby boomers, people born from 1945 through 1965 be tested once for hepatitis C

Why Screen All Baby Boomers?
Although the authors of the recommendations regarding screening for HCV infection note that the prevalence of HCV infection in the United States appeared to peak in 2001, there is another clear trend in the epidemiology of HCV infection that merits close attention. Persons born between 1945 and 1965 comprise approximately 27% of the total population of the United States, but they account for a disproportionate share of cases of HCV infection. The prevalence of HCV infection in this age group is 3.25%, and approximately three quarters of active HCV infection cases are encountered among persons born between 1945 and 1965.
Moreover, and more important, persons who are currently in the fifth through seventh decades of life at this time are at the highest risk for complications from HCV infection. They account for 73% of mortality due to HCV infection, and this group is also at the highest risk for hepatocellular carcinoma and cirrhosis. Therefore, the number of patients needed to treat with anti-HCV therapy in order to prevent additional cases of mortality is lower in this specific older cohort of adults compared with younger adults.

Therefore, it is not only the epidemiologic data that drive the new HCV screening recommendations from the USPSTF, but also an expectation that treatment of heretofore undiagnosed HCV infection can put a substantial dent in the broad clinical impact of HCV. The new recommendations call for 1-time screening for all adults born between 1945 and 1965 (B recommendation: high certainty that the net benefit is moderate, or moderate certainty that the net benefit is moderate to substantial). The anti-HCV antibody is test the best screening tool for these adults.

Bats a possible source for HCV-like viruses?
Hepatitis C: Closing in on its viral origins
Just like the bat viruses, these too exhibited a large degree of genetic variability, hinting at an enduring history of infection. Future studies could see rodents emerge as the confirmed source of the virus

None of the rodent sequences was more related to HCV than the horse hepaciviruses, but one of the co-authors of this study, Prof Peter Simmonds from the University of Edinburgh, thinks that the large degree of variability observed in these rodent viruses might prove significant...
Continue reading....

New Drug Approved November/December 2013

Sofosbuvir FDA Approved In U.S. and Canada
Gilead's Sovaldi (Sofosbuvir) Is Now FDA Approved
– Sovaldi Approved for Use in Genotypes 1, 2, 3 or 4 –
– High Cure Rates (SVR12) and Shortened, 12-Week Course of Therapy for Many Patients –
– First Ever Oral Treatment Regimen for Genotypes 2 or 3 –
– First Regimen for Patients Awaiting Liver Transplantation to Prevent HCV Recurrence –

Sovaldi is approved in HCV genotypes 1 and 4, treatment-naïve adults in combination with PEG-IFN and ribavirin and the first approved interferon-free treatment regimen for people with HCV genotypes 2 and 3. Overall cure rates are at 80%, response rates and treatment duration varies, depending on genotype, viral and host factors.
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Simeprevir FDA Approved
OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C
Johnson & Johnson's protease inhibitor OLYSIO (Simeprevir) is approved for the treatment of HCV genotype 1, in combination with peginterferon alfa and ribavirin in adults with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin.

Simeprevir was approved in Japan this past September 2013, and in Canada on November 20th.

May 4 2014
Yellow Blood: Hepatitis C and the Modernist Settlement in Japan.
In 1964, HCV infection via direct blood-to-blood contact with contaminated blood was happening wherever medicine could afford transfusion technology and wherever blood products and hypodermic syringes were in use as therapies or therapy delivery systems. Although the hepatitis C virus probably originated in West Africa in the late 15th century, its global sweep and pandemic status in the world today are both intimately linked with progression of the modernist settlement: the dualistic epistemological structure of modernity in which science and technology are divided from and purified of culture and politics. 

June 20 2014
Boehringer Ingelheim exits hepatitis C field, pulls regulatory filings for faldaprevir
Boehringer Ingelheim on Friday announced that following a strategic review the company has decided against moving forward in the field of hepatitis C. As such, the drugmaker indicated that it will withdraw all regulatory filings for faldaprevir, which had been granted accelerated assessment by the European Medicines Agency, and will discontinue further development of the protease inhibitor.

August 13 2014
PegLambda Discontinued by BMS
We have decided to discontinue the Lambda HCV development program and will no longer be seeking regulatory review of Lambda, globally. We would like to take this opportunity to reinforce that our late-stage HCV DAA development program remains unaffected.

August 14 2014
Vertex to stop selling hepatitis C drug Incivek
Vertex’s decision to stop selling Incivek in the United States as of Oct. 16 was conveyed in a Monday letter to health care providers written by Charles Johnson, the company’s vice president of global medical affairs.

Oct 7 2014
Bristol-Myers withdraws FDA NDA for asunaprevir
Bristol-Myers Squibb (BMY) has decided that it will not pursue U.S. Food and Drug Administration (FDA) approval of the dual regimen of daclatasvir and asunaprevir for the treatment of HCV genotype 1b patients in the United States and has therefore withdrawn its new drug application (NDA) for asunaprevir, an NS3/4A protease inhibitor.

Oct 10 2014

U.S. Food and Drug Administration Approves Gilead’s Harvoni® (Ledipasvir/Sofosbuvir), Once-Daily Single Tablet Regimen for the Treatment of Genotype 1 Chronic Hepatitis C
Harvoni is the first combination pill approved to treat chronic HCV genotype 1 infection. It is also the first approved regimen that does not require administration with interferon or ribavirin, two FDA-approved drugs also used to treat HCV infection.

Both drugs in Harvoni interfere with the enzymes needed by HCV to multiply. Sofosbuvir is a previously approved HCV drug marketed under the brand name Sovaldi. Harvoni also contains a new drug called ledipasvir.
Continue reading...

Oct 20 2014
New Report BMS-986094 (halted in 2012)
HCV nucleotide analogue polymerase inhibitor associated with cardiac dysfunction
Fourteen of 34 patients with hepatitis C virus infection who were treated with the novel nucleotide analogue polymerase inhibitor BMS-986094 had some evidence of cardiac dysfunction, according to a new report.

Oct 26 2014
3 die after being administered SOVRIAD™ (simeprevir sodium) Hepatitis C drug
The health ministry said Friday three people have died after taking the hepatitis C drug Sovriad, and it has ordered the distributor to revise the drug packaging to say usage should stop when indicated by a patient blood test. 

Nov 6 2014
FDA approves Medivir's Olysio (simeprevir) in combination with Gilead Sciences' Sovaldi (sofosbuvir)
-Expanded indication includes both treatment-naïve and treatment-experienced adult patients with or without cirrhosis-

Medivir AB (Nasdaq Stockholm:MVIR) announces that the U.S. Food and Drug Administration (FDA) has approved Olysio® (simeprevir) in combination with sofosbuvir as an all-oral, interferon- and ribavirin-free treatment option for genotype 1 chronic hepatitis C infection in adult patients as part of a combination antiviral treatment regimen

Nov 18 2014
European Commission Grants Marketing Authorization for Gilead's Harvoni (Ledipasvir/Sofosbuvir), the First Single Tablet Regimen to Treat the Majority of Chronic Hepatitis C Patients With Genotype 1 and 4

December 19 2014
FDA approves VIEKIRA Pak
FDA Approves AbbVie Combo Hepatitis C Treatment
On December 19, 2014, FDA approved VIEKIRA Pak (ombitasvir, paritaprevir, ritonavir fixed dose combination tablets copackaged with dasabuvir tablets) for use with or without ribavirin for the treatment of patients with genotype 1 chronic hepatitis C virus (HCV) infection including those with compensated cirrhosis.

Medscape - Free registration is required to view slides
Slideshow 25-year span of HCV
The glorious accomplishments in this field are nicely summarized as "the arc of a medical triumph" by Chung and Baumert, highlighting the short, 25-year span from the discovery of hepatitis C virus (HCV) to treatment that now achieves cure in more than 95% of patients with a single oral pill taken once daily for 8-12 weeks.

April 16 2015
FDA approved changes to the Olysio (simeprevir) package insert to include two new Warnings and Precautions 

Mar 21 2015
FDA Update - Important safety information: Harvoni , and Sovaldi‏
Serious and Life-Threatening Cases of Symptomatic Bradycardia as well as One Case of Fatal Cardiac Arrest Reported with Coadministration of amiodarone with either Harvoni® (ledipasvir and sofosbuvir fixed-dose combination) or with Sovaldi® (sofosbuvir) in combination with another direct acting antiviral.

Mar 19 2015
Boceprevir Expected to be Discontinued by December 2015
Merck expects to discontinue the manufacturing and distribution of its inhibitor boceprevir for the treatment of hepatitis C virus by December, according to a company spokesperson.

July 24 2015
Technivie and Daklinza
At the end of July the FDA approved two new drugs for hepatitis C, one for genotype 3 called Daklinza "Daclatasvir" in combination with sofosbuvir and the other is Technivie (ombitasvir, paritaprevir, ritonavir) for genotype 4. To view package insert, dosage, warnings, drug interactions and side effects for the newly approved drugs, click here.

The Food and Drug Administration (FDA) announced that Rebetol(ribavirin; Merck) capsules and PegIntron (peginterferon alfa-2b; Merck) for Injection are being discontinued. The decision is business-related and not due to safety or efficacy issues with the drugs.

Nov 30, 2015 - Imported Generic hepatitis C Drugs - Buyers Club
Real life Dallas Buyers Club operation helps hepatitis C patients with free drugs
Which is why two months ago, as Fairfax Media revealed,  a campaigning group of sufferers and doctors launched a Dallas Buyers Club operation to source and test generic versions of Gilead's drugs – Sovaldi and Harvoni – from manufacturers in China, India and Bangladesh for about $20 a pill.
Since the FixHepC Buyers Club was started by father-and-son team Dr John and Dr James Freeman, tens of thousands of people in more than 100 countries have made several million visits to the website.

Jan 28 2016​
Merck Receives FDA Approval of ZEPATIER™ (elbasvir and grazoprevir) for the Treatment of Chronic Hepatitis C Virus Genotype 1 or 4 Infection in Adults Following Priority Review
ZEPATIER Achieves High Cure Rates (SVR12) in Broad Range of Patients with Chronic Hepatitis C Infection, Including Those with Compensated Cirrhosis, Renal Impairment of Any Degree and HIV-1/HCV Co-infection​
The list price for Zepatier will be $54,600 for a 12-week regimen, which Merck said it expects "to be in the range of net prices" for comparable treatments.​
Prescribing Information for ZEPATIER (elbasvir and grazoprevir)
Patient Information for ZEPATIER 

April 2016
25 Years From Discovery To Cure: The Hepatitis C Story |
Nezam Afdhal | TEDxOxford
The discovery of the hepatitis C virus in 1989 and 25 years of has led to new treatments that can now cure almost all patients with hepatitis C and have the ability to reach almost 200 million people globally. Dr. Afdhal discusses how discovery of the virus lead to understanding the global epidemiology and modes of spread of hepatitis C and the recognition that it was the commonest cause of cirrhosis, liver cancer and need for liver transplantation. The development of model systems to look at viral replication led to treatments initially with injectable interferon with low cure rates and poor patient tolerability to new all oral direct acting anti-viral agents which can cure patients with a simple, safe and effective 8 – 12 week treatment. Finally Dr. Afdhal discusses how these treatments have changed the discussion in the US on the cost of new medications and the ongoing plans to bring these expensive treatments to developing countries with high hepatitis C burden.

Medical practices, not lifestyle choices, are actually behind the generation’s high HCV rates, so now will you go get tested?

HCV epidemic in North America peaked between 1940 and 1965 with medical procedures likely source of most infections
Most baby boomers infected in hospital and by reused medical syringes, not injecting drug use or risky sex..

June 2016
June 27
Regulus Therapeutics (RGLS) Announces Clinical Hold on RG-101
Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced it received verbal notice from the U.S. Food and Drug Administration (FDA) that its Investigational New Drug (IND) for RG-101 for the treatment of chronic hepatitis C virus (HCV) infection has been placed on clinical hold. Regulus anticipates it will receive a formal clinical hold letter from the FDA within 30 days and plans to work diligently with the agency to seek the release of the clinical hold​

January 31, 2017
Regulus Announces Continuation of RG-101 Clinical Hold - FDA requests longer-term follow-up data from ongoing studies

June 28 2016
FDA Approved: Epclusa® (Sofosbuvir/Velpatasvir
At the end of June the FDA Approved Gilead's Epclusa® (Sofosbuvir/Velpatasvir) to treat Genotype 1-6, for prescribing information click here, in addition on July 8th the European Commission granted marketing authorization for Epclusa, followed yesterday by approval in Canada.

HCV Guidelines
A great source for learning all about treatment can be found in the HCV Guidelines, this ever changing document is updated when new HCV drugs are approved, and new real world data is established. Last week it was updated to include Epclusan ®.
Stay current with all guideline updates, click here.

July 2016
July 25, 2016
VIEKIRA XR is a once-daily, extended-release co-formulation of the active ingredients in VIEKIRA PAK (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) and is for the treatment of patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated cirrhosis (Child-Pugh A). VIEKIRA XR is not for people with decompensated cirrhosis.

VIEKIRA XR differs from VIEKIRA Pak in that all of the HCV antiviral drugs are now combined in one fixed dose combination tablet for once daily dosing. The daily mg dose of dasabuvir is higher, and dasabuvir is administered once daily as part of the fixed dose combination.

The Controversy - Drug Cost

Epclusa Cost
Bloomberg reported Epclusa will cost $74,760 for a 12-week course of treatment, less than Gilead’s Sovaldi Harvoni, at $84,000 or $94,500 before any discounts, read the article here.

Canada; New Health Canada approved drug costs more than $700 a pill. The list price in Canada is set at $60,000 for a 12-week course

September 2016
Inventor of Hepatitis C Cure (Sovaldi) Wins Lasker Award
Michael Sofia, has netted a prestigious Lasker Award for revolutionizing hepatitis C care. Lasker Awards, which recognize scientists’ major contributions to medical science or those who have performed public service on behalf of the field, are often considered a pit stop on the way to a Nobel Prize.

Oct 2016
FDA MedWatch/Direct-Acting Antivirals for Hepatitis C: Drug Safety Communication - Risk of Hepatitis B Reactivating
The FDA is warning about the risk of hepatitis B virus (HBV) becoming an active infection again in any patient who has a current or previous infection with HBV and is treated with certain direct-acting antiviral (DAA) medicines for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAA medicines resulted in serious liver problems or death. HBV reactivation usually occurred within 4-8 weeks.

Oct 27, 2016 - Generic imported DAAs - Buyers Club
Buyers’ Clubs: Generic versions of HCV drugs resulted in very high cure rates
Keith Alcorn
Use of generic versions of direct-acting antivirals resulted in very high cure rates for people who obtained the products through three buyers’ clubs, indicating that the generics products are effective, according to three presentations at the International Congress on Drug Therapy in HIV Infection in Glasgow this week.
People who purchased the drugs were cured of hepatitis C at a cost of around $700-$900, Dr Andrew Hill of St Stephen’s AIDS Trust, London, reported in three poster presentations at the conference.
Continue reading ....

Nov 12, 2016
MK3 (MK-3682/grazoprevir/ruzasvir1)
AASLD 2016 Merck's HCV Triple-Combination High Rates of SVR In Genotypes 1, 2 or 3 Infection

Nov 2016
Liver Cancer After Treatment For Hepatitis C
This collection of research articles is updated as information is made available, accessed from online journals, media articles, and conferences with some articles overlapping.

Dec 8, 2016
Gilead Submits New Drug Application to U.S. Food and Drug Administration for the Investigational Single Tablet Regimen Sofosbuvir/Velpatasvir/Voxilaprevir
Gilead Sciences, Inc. announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily single tablet regimen containing sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg (SOF/VEL/VOX) for the treatment of direct-acting antiviral (DAA)-experienced chronic hepatitis C virus (HCV)-infected patients. The data submitted in the NDA support the use of the regimen for 12 weeks in DAA-experienced patients with genotype 1 to 6 HCV infection without cirrhosis or with compensated cirrhosis.

Jan 2017
Regulus Announces Continuation of RG-101 Clinical Hold - FDA requests longer-term follow-up data from ongoing studies

Feb 2017
Thousands of British Columbians living with hepatitis C will have better access to treatment as a result of successful negotiations brokered by the pan-Canadian Pharmaceutical Alliance (pCPA).
“This agreement changes the landscape for hepatitis C patients living in B.C.,” said Health Minister Terry Lake. “Not only are there four new treatment options for what is now a curable virus, but the savings that were negotiated will allow us to cover treatment options for all hepatitis C patients – rather than just those in more advanced stages of the disease.”

TECHNIVIE (fixed-dose combination of ombitasvir, paritaprevir, and ritonavir) label was updated to expand the indication
On February 27, 2017 the TECHNIVIE  (fixed-dose combination of ombitasvir, paritaprevir, and ritonavir) label was updated to  expand the indication to patients with genotype 4 chronic hepatitis C virus infection (HCV) with compensated cirrhosis. Below is a summary of the major changes to the label based on the results of the AGATE-1 trial in HCV genotype 4 infected adults with compensated cirrhosis who are either treatment-naïve or pegylated interferon/ribavirin treatment experienced. Other minor revisions were made to the table including updates to section 8.1 Pregnancy and 8.2 Lactation.

Feb 2, 2017
U.S. FDA Grants Priority Review to AbbVie’s Investigational HCV Regimen of Glecaprevir/Pibrentasvir (G/P)

Of Interest
March 8, 2017
Full Text Article - Newer medications can cure HCV infections

February 21, 2017
Novel emerging treatments for hepatitis C infection: a fast-moving pipeline
This update reviews some upcoming therapies for the treatment of chronic hepatitis C.

With hep C franchises languishing, Merck’s MK-3682 goes from blockbuster to bomb
by John Carroll
A little less than three years after acquiring the hepatitis C drug MK-3682 (uprifosbuvir) in its $3.85 billion buyout of Idenix, Merck’s prospects in the field have cooled dramatically, and its once great hopes for the drug have been reduced to nearly nothing.
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Liver Specialist Refutes Study Claiming Hepatitis C Drug Dangers
The ISMP report cited 524 cases of liver failure and 1,058 cases of severe liver damage in patients taking one of nine DAAs.

2017 - Of Interest
Current therapy for chronic hepatitis C: The role of direct-acting antivirals.
Antiviral Res. 2017 Jun;142:83-122. doi: 10.1016/j.antiviral.2017.02.014. Epub 2017 Feb 24.
• HCV genotype-specific drugs evolve to pan-genotypic drugs.
• Drug potency increases from moderate (∼60%) to high (>90%) levels of sustained virologic response.
• Treatment durations are shortened from a 48-week to 12-week or 8-week period.
• HCV therapies based upon multiple pills per day are simplified to a single pill per day.
• HCV therapies are administered orally regardless of prior treatment history and cirrhotic status.

FDA Update
April 7, 2017
FDA Approves HCV Sovaldi and Harvoni For Children Ages 12 to 17

November 15, 2017
Sep 21, 2017
June 2017
Rebuttal over Cochrane Review of DAAs
View each rebuttal and all ongoing media coverage. In June the HCV community was blindsided when an article with a somewhat "clickbait" headline was released by The Guardian. The Guardian reported on a systematic review published by the Cochrane Collaboration that suggested achieving SVR (cure) for patients using hepatitis C direct-acting antivirals (DAAs) doesn't correlate with any long term benefits...

July 18, 2017
Gilead's VoseviTM (Sofosbuvir/Velpatasvir/Voxilaprevir) FDA Approved for Re-Treatment of Adults with HCV
- Vosevi is the First Once-daily Single-Tablet HCV Regimen Approved as Salvage Therapy for Certain Patients and Completes Gilead's Portfolio of Sofosbuvir-based HCV Direct-acting Antiviral (DAA) Treatments -
FOSTER CITY, Calif.--(BUSINESS WIRE)--Jul. 18, 2017-- Gilead Sciences, Inc. (NASDAQ: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved VoseviTM (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) tablets, a single-tablet regimen for the re-treatment of chronic hepatitis C virus (HCV) infection in adults with genotype 1, 2, 3, 4, 5 or 6 previously treated with an NS5A inhibitor-containing regimen, or with genotype 1a or 3 previously treated with a sofosbuvir-containing regimen without an NS5A inhibitor. The approval is based on data from the Phase 3 POLARIS-1 and POLARIS-4 studies, which evaluated 12 weeks of Vosevi in direct-acting antiviral-experienced chronic HCV-infected patients without cirrhosis or with compensated cirrhosis.

Aug 1, 2017
FDA Approves Expanded Labeling for Epclusa® for Hepatitis C in Patients Co-Infected with HIV

August 3, 2017
AbbVie Receives U.S. FDA Approval of MAVYRET™ (glecaprevir/pibrentasvir)
The U.S. Food and Drug Administration today approved Mavyret (glecaprevir and pibrentasvir) to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret is also approved for adult patients with HCV genotype 1 infection who have been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor but not both.

Monthly WAC price for HCV Drugs Including Mavyret
Tweeted by Henry E. Chang

Aug 4, 2017
Of Interest
The changing HCV treatment cascade
The shift in the HCV treatment paradigm is now heavily patient-centric and dependent on genotype, presence of cirrhosis, HIV coinfection, potential drug interactions, previous treatment failure, and renal impairment. In its simplest form, the backbone of HCV treatment requires a combination DAA with or without the addition of ribavirin and duration varies on the presence of cirrhosis.

September 11, 2017
J&J unit ends hepatitis C drug development in crowded market
Janssen Sciences Ireland UC (Janssen), today announced a strategic decision to discontinue further development of the investigational hepatitis C treatment regimen JNJ-4178, a combination of three direct acting antivirals - AL-335, odalasvir and simeprevir. The ongoing phase II studies with JNJ-4178 will be completed as planned, but there will be no additional development thereafter. This decision was made in light of the increasing availability of a number of highly effective therapies addressing the medical need in hepatitis C.

Sept 28, 2017
Is HCV Drug Development Nearing Its End?
Two new FDA approvals fill medical gaps, but access to treatment remains a challenge

Sept 29,2017
Merck Discontinues MK-3682B and MK-3682C Development Programs
Merck to discontinue the development of the investigational combination regimens MK-3682B (grazoprevir/ruzasvir/ uprifosbuvir) and MK-3682C (ruzasvir/uprifosbuvir) for the treatment of chronic hepatitis C virus (HCV) infection.

October 2017 - Generic imported DAAs
High sustained virological response rates using imported generic direct acting antiviral treatment for hepatitis C
High prices of direct acting antivirals (DAAs) for hepatitis C virus (HCV) can lead to restrictions on access to treatment in high- and middle-income countries. An increasing number of people in these regions are treating their HCV infection with generic drugs produced in India, China, Bangladesh or Egypt. This analysis assessed the efficacy of generic imported DAAs

November 16, 2017
HCV Timeline
To get insight into what the recent approvals and pricing structure of new DAA therapies means to treatment of HCV, read the following editorial at Healio, from Michael S. Saag, MD,  here.”

Click on HCV Timeline To Enlarge Image, Or View Image, here.....

December 8, 2017
Liver cancer incidence after HCV therapy linked to risk factors, not treatment
Li DK, et al. Hepatol. 2017;doi:10.1002/hep.29707.
Direct-acting antiviral treatment for hepatitis C did not correlate with an increased risk for hepatocellular carcinoma in a large cohort study of both treated and untreated patients with or without cirrhosis. Those with incident HCC after DAA treatment had higher risk factors at baseline. “There was no increased risk for HCC as a result of having received DAA therapy whatsoever,” Raymond T. Chung, PhD, director of Hepatology and Liver Center at Massachusetts General Hospital, told Healio Gastroenterology and Liver Disease. “The risk was related to their preexisting likelihood of developing HCC. The fact that HCC developed post-DAA, we think, is more likely to be an accident of timing than the idea that it's related to receipt of DAA — these persons were at risk for HCC whether they received DAAs or not.”
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January 5, 2018

Reducing the cost of new hepatitis C drugs
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"

Page updated January 2017

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