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Alan Franciscus

Editor-in-Chief

HCV Advocate



Friday, October 16, 2015

Achillion Announces That Janssen Has Initiated a Phase 2a Study to Evaluate the Combination of AL-335, Odalasvir (ACH-3102), and Simeprevir for the Treatment of Genotype 1 Chronic HCV

Once Daily Triple Direct-Acting Antiviral Regimen Will be Evaluated for Treatment Durations of Four, Six or Eight Weeks


NEW HAVEN, Conn., Oct. 16, 2015 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) announced today that Alios Biopharma Inc., part of the Janssen Pharmaceutical Companies (Janssen) has initiated treatment in a phase 2a clinical trial to evaluate the safety, pharmacokinetics and efficacy of AL-335, odalasvir (also known as ACH-3102), and simeprevir in treatment-naïve patients with genotype 1 chronic hepatitis C virus (HCV) infection.
This phase 2a study is a randomized, open-label, three-arm study of AL-335, a nucleotide-based HCV NS5B polymerase inhibitor, odalasvir, an HCV NS5A inhibitor, and simeprevir, an HCV NS3/4A protease inhibitor. Patients will be randomized to one of three treatment arms and receive once daily treatment for a duration of four, six or eight weeks. The primary objective of the study is to establish the safety of the treatment regimen with secondary endpoints consisting of pharmacokinetics, the proportion of subjects achieving sustained viral response (SVR), and the effect on the viral resistance profile after treatment. The study is expected to enroll approximately 60 patients across the three treatment arms.
As previously announced on May 19, 2015, Achillion has granted Janssen an exclusive, worldwide license to develop and, upon regulatory approval, commercialize HCV products and regimens containing one or more of Achillion's HCV assets which include odalasvir (ACH-3102), ACH-3422, and sovaprevir.
Further information about the study can be found at www.clinicaltrials.gov. Study identifier: NCT02569710.

How insurance providers deny hepatitis C patients lifesaving drugs - Doctors say up to 80 percent of patients are denied expensive but effective drugs like Harvoni

Amber Rojas was almost eight months pregnant when she learned she had hepatitis C. After her daughter was born on Dec. 23, 2014, Rojas had hoped to start treatment with a newly approved, highly effective drug called Harvoni.
After filing for prior authorization and waiting for months, the 34-year old mother received an unwelcome letter on August 27, 2015 — her treatment request had been denied because her liver was still too healthy. Rojas said that even though she felt very sick with flu-like symptoms, her insurance provider deemed her “not sick enough to qualify.”
Rojas is one of an estimated 3.2 million Americans with hepatitis C, an infection that attacks the liver. In the United States, hepatitis C kills more people every year than HIV. Drugs like Harvoni promise to cure more than 90 percent of patients, yet many insurance providers authorize treatment only if a patient has extensive liver damage, or a fibrosis score of 3 or 4.

Hepatitis C rates exploding among suburban N.J. heroin users, study finds

Researchers recently confirmed what many in the medical and drug treatment community had feared: Rates of Hepatitis C are skyrocketing among New Jersey's suburban heroin users, particularly among the young.

A study that tested 861 suburban heroin users admitted to Princeton House, an inpatient treatment center, found that 44 percent tested positive for Hepatitis C, a potentially fatal but treatable disease that affects the liver. Of those, nearly two-thirds were under the age of 35.

"It's crazy. I'm not sure I even expected to see the number that high," said Ronald Nahass, an infectious disease specialist with ID Care, who conducted the study with researchers from Princeton House. "On the other hand, I don't know that I'm terribly surprised. We've noticed this happening, and it really wasn't being recognized, which is really upsetting me, frankly."

Read more....

Thursday, October 15, 2015

President coming to Charleston Wednesday

This is encouraging that the President is coming to West Virginia to talk about an outbreak of prescription drug use--hopefully it will lead to support for needle exchange and funding for support services.  Alan

CHARLESTON, W.Va. (WSAZ) -- Battling heroin addiction by giving addicts clean needles may sound counter-productive, but Charleston is now the second city in West Virginia working to authorize a needle-exchange program.

Just like the program that started last week in Huntington, it will allow people to exchange dirty needles for clean ones.

The bill was introduced at Tuesday night's city council meeting.

The goal is to help addicts get information on treatment and recovery as well as stopping the spread of diseases like hepatitis.

Read more.....

Hepatitis C May Increase Risk of Heart Disease

Positive hepatitis C infection may increase risk for liver damage as well as future heart problems, according to findings published in The Journal of Infectious Diseases.  

Researchers from Johns Hopkins Medicine evaluated almost 1,000 men aged 40 to 70 years with or without human immunodeficiency virus (HIV), of which 87 also had hepatitis C in order to measure associations between hepatitis C with coronary atherosclerosis. About 750 men participating in the study also underwent CT angiography. The participants, who did not have overt existing heart disease, were recruited from the Multicenter AIDS Cohort Study, a larger study focused on men who have sex with men.

Prior research demonstrated that people with HIV already have an elevated risk for heart disease, but the researchers believe their findings here offer strong support for hepatitis C also contributing to cardiovascular damage independent of HIV status.

Read more....

Tuesday, October 13, 2015

Can Non-Invasive Tests Assess Fibrosis in Hepatitis?

 Percutaneous liver biopsy is a proven way to rate the fibrosis stage both in hepatitis in chronic hepatitis C patients and hepatitis B  patients. But it is uncomfortable for patients, risks complications and is prone to assembling errors.

Reporting at ID Week 2015 in San Diego, CA, Tuma Demirdal, DR, and colleagues at the Katip Celebi University in Izmir, Turkey compared these invasive tests with non-invasive methods.

They looked at 236 patients with chronic hepatitits C and hepatitis B who had ultrasound guided liver biopsy over a seven year period Histological grading of necroinflammation and fibrosis ere performed according to Knodell an ISAK scoring systems. APRI, n-APRI, FIB-4, FI scores were calculated.

  Read more....

SNAPSHOTS —Alan Franciscus, Editor-in-Chief

This month’s (October 2015) column features a variety of studies, including treatment of people with advanced liver disease, treating people who have not achieved a cure with direct acting antiviral therapy, including people who had developed RAVs.

Article:  Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease—M Charlton et al. 

Source:  Gastroenterology. 2015 Sep;149(3):649-59. doi: 10.1053/j.gastro.2015.05.010. Epub 2015 May 15.

Results and Conclusions
This was a phase 2 study of 337 patients with decompensated cirrhosis with genotype 1 (332 patients) and genotype 4 (5 patients) who received 12 or 24 weeks of Harvoni plus ribavirin twice daily.  None of the patients previously treated developed resistance to sofosbuvir.  People who had been previously treated with an NS5A inhibitor were excluded from the study. 

There were two groups in the study:
  •  Group A, who had NOT had a liver transplant: 59 patients with Child-Pugh class B cirrhosis and 49 patients with Child-Pugh class C  cirrhosis*
  •  Group B who HAD undergone liver transplantation:  111 patients without cirrhosis, 51 patients with Child-Pugh class A cirrhosis, 52 with Child-Pugh class B cirrhosis, 9 with Child-Pugh class C cirrhosis, and 6 with fibrosing cholestatic hepatitis*

 *Child-Pugh cirrhosis scoring is a system that uses various types of blood markers and liver disease progression such as ascites to evaluate a patient to establish the severity of cirrhosis and long-term patient survival.  The classes are A, B and C with A as the less severe and C as the most severe.  Cholestatic hepatitis is bile duct blockage with fibrosis.

Group A and B had 12- and 24-week treatment arms, but cure rates were similar regardless of treatment duration.
     
 The Bottom Line
In group A (those who had not received a liver transplant), the cure rate was 86% to 89%.  In group B (transplant group) the people who did not have cirrhosis or Class A cirrhosis—the cure rate was 96% to 98%.  Furthermore, in group B with class B cirrhosis (compensated) the cure rate was 85% to 88%, and those with class C cirrhosis (moderate impairment) achieved 60% to 75% cure rates. The people who had fibrosing cholestatic hepatitis achieved 100% cure rates.  There were 13 patients (4%) who discontinued treatment.  Ten patients died in the trial.  The deaths were mainly attributed to complications from hepatic decompensation or end-stage liver disease.

Editorial Comment
In the past, people with these types of severe disease progression have been very difficult to cure or even treat, but now with these ‘miracle’ drugs many people now have a second chance at life.  Now if we could just get these drugs to everyone with hepatitis C before this stage, we would eliminate the need to treat at these stages of disease severity. 

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Article:  Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent—X Forns et al.

Source:  J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.

Results and Conclusions
There were 79 HCV genotype 1 patients in the study. 
  • Sixty-six patients who had been previously treated patients with an NS3/4A protease inhibitor but had not been cured. 
  • Of the 13 remaining patients, 12 had discontinued treatment due to side-effect(s). 
  • Thirty-four patients had NS3 resistance-associated variants (RAVs), and eight patients had NS5A RAVs. 
  • Eight patients treated with the combination of grazoprevir and elbasvir plus ribavirin twice daily.

 The Bottom Line
The overall cure rates were 96% (76 of 79 patients)—this included 93% (63 of 66 patients) of the genotype 1a, one hundred percent of the patients (43 of 43 patients) who DID NOT have RAVs achieved a cure.  Ninety-one percent of those who DID have NS3 RAV’s were cured and 75% (6 of 8 patients) of those who had NS5A RAVs were cured.  Of those with cirrhosis 94% were cured with this combination. 

Editorial Comment
The addition of ribavirin to grazoprevir and elbasvir works to help cure resistance-associated variants in people who have been previously treated but who have not been cured.  It is also good strategy to treat other negative predictors to current  medications.
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Article:  Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens—D Wyles et al.  

Source:  Hepatology. 2015 Jun;61(6):1793-7. doi: 10.1002/hep.27814. Epub 2015 Apr 27.

Results and Conclusions
There were 51 genotype 1 patients enrolled in the study (Note: one patient was incorrectly typed as genotype 1, but was subsequently correctly genotyped as genotype 3).  All of the patients in this trial were previously treated with a sofosbuvir containing regimes in Gilead’s phase 1 or phase 2 studies.  The treatment duration in this study was 12 weeks. 
Breaking it down by type of prior type of non-response:
  • 25 pts (49%) had previously received sofosbuvir plus pegylated interferon plus ribavirin
  • 20 pts (39%) had previously received sofosbuvir plus ribavirin
  • 5 pts (10%) received sofosbuvir (sugar pill/placebo) plus pegylated interferon and ribavirin
  • 1 pt (2%) received GS-0938 only fourteen patients (27%) had compensated cirrhosis.

 The Bottom Line
The total number of patients who achieved a cure was 98% (50 of 51 patients).  Among those who had received a prior course of sofosbuvir 98% (44 of 45) were cured.  The only patient who did not achieve a cure was the patient who was originally misdiagnosed as a genotype 1. 

The most common side effects were fatigue, headache and diarrhea.  The patients in this trial are considered some the most difficult to treat—those who have not achieved a cure with a previous course of a direct acting antiviral medication, those with cirrhosis, and people with resistant antiviral variants (RAVs). 

Editorial Comment
The addition of ledipasvir and ribavirin to sofosbuvir increased the cure rates to 100% for genotype 1.  Excellent results!  This is a good strategy with another type of direct acting antiviral to stop the virus from replicating and escaping.

Gilead, Merck, AbbVie, Janssen, and Achillion are working on other HCV drugs that have a higher barrier to resistance to avoid the development of resistance and to work for people who are not responding to the current medications.