Friday, October 19, 2018

HCV Drug Ravidasvir is on the List of Proposed Priority Review by the Chinese Food and Drug Administration

Ascletis’Ravidasvir NDA Proposed for Priority Review by the CFDA
Hangzhou and Shaoxing, China (Oct. 18, 2018) - Ascletis Pharma Inc. (1672.HK) announces today the New Drug Application (NDA) of Ravidasvir is on the List of Proposed Priority Review, according to the public notification by the China Food and Drug Administration (CFDA) on Oct 17th, 2018. Such Priority Review will accelerate Ravidasvir NDA approval process significantly. Ravidasvir is Ascletis’ second category 1 drug for Hepatitis C.

Ravidasvir is a next-generation, best-in-class and pan-genotypic HCV NS5A inhibitor with a high genetic barrier to resistance. Ravidasvir in combination with Ganovo® (RDV/DNV Regimen) is the first all-oral interferon-free HCV regimen developed by a domestic company in China. Phase II/III clinical trial conducted in China has shown that RDV/DNV Regimen demonstrated a cure rate of 99 % (SVR12) with a short treatment duration of 12 weeks in genotype 1 patients. In patients with baseline NS5A resistance mutations, RDV/DNV Regimen demonstrated a cure rate of 100% (SVR12). Ascletis received the acceptance letter from the CFDA for Ravidasvir NDA on Aug. 1, 2018.

”We launched our first breakthrough HCV regimen 3 months ago. Ganovo Regimen has been well recognized and accepted by the doctors and experts,” said Jinzi J. Wu, Ph.D., Ascletis’ founder, Chairman and CEO. ”The Priority Review for Ravidasvir NDA will accelerate the launch of Ascletis’ all-oral regimen. This will enable Ascletis to soon provide two breakthrough HCV treatment regimens for Chinese patients and further strengthen our leadership position as an integrated solution provider in HCV treatment in China.” 

Of Interest
April 12, 2018 An affordable hepatitis C combination treatment including the new drug candidate ravidasvir has been shown to be safe and effective, with extremely high cure rates for patients, including hard-to-treat cases, according to interim results from the Phase II/III STORM-C-1 trial presented by the non-profit research and development organisation Drugs for Neglected Diseases initiative (DNDi) at the International Liver Conference in Paris.  The results indicate that the sofosbuvir/ravidasvir combination is comparable to the very best hepatitis C therapies available today, but it is priced affordably and could allow an alternative option in countries excluded from pharmaceutical company access programmes,” said Dr Bernard Pécoul, Executive Director, DNDi….

Long‐term prognostic value of the FibroTest in patients with non‐alcoholic fatty liver disease, compared to chronic hepatitis C, B, and alcoholic liver disease

Long‐term prognostic value of the FibroTest in patients with non‐alcoholic fatty liver disease, compared to chronic hepatitis C, B, and alcoholic liver disease 
Mona Munteanu Raluca Pais Valentina Peta Olivier Deckmyn Joseph Moussalli Yen Ngo Marika Rudler Pascal Lebray Frederic Charlotte Vincent Thibault

First published: 17 October 2018 https://doi.org/10.1111/apt.14990

Full-text

Summary
Background
Although the FibroTest has been validated as a biomarker to determine the stage of fibrosis in non‐alcoholic fatty liver disease (NAFLD) with results similar to those in chronic hepatitis C (CHC), B (CHB), and alcoholic liver disease (ALD), it has not yet been confirmed for the prediction of liver‐related death.

Aim
To validate the 10‐year prognostic value of FibroTest in NAFLD for the prediction of liver‐related death.

Method
Patients in the prospective FibroFrance cohort who underwent a FibroTest between 1997 and 2012 were pre‐included. Mortality status was obtained from the physician, the hospital or the national register. Survival analyses were based on univariate (Kaplan‐Meier, log rank, AUROC) and multivariate Cox risk ratio taking into account age, gender and response to anti‐viral treatment as covariates. The comparator was the performance of the FibroTest in CHC, the most validated population.

Results
7082 patients were included; 1079, 3449, 2051, and 503 with NAFLD, CHC, CHB, and ALD, respectively. Median (range) follow‐up was 6.0 years (0.1‐19.3). Ten year survival (95% CI) without liver‐related death in patients with NAFLD was 0.956 (0.940‐0.971; 38 events) and 0.832 (0.818‐0.847); 226 events; P = 0.004) in CHC. The prognostic value (AUROC / Cox risk ratio) of FibroTest in patients with NAFLD was 0.941 (0.905‐0.978)/1638 (342‐7839) and even higher than in patients with CHC 0.875 (0.849‐0.901; P = 0.01)/2657 (993‐6586).

Conclusions
The FibroTest has a high prognostic value in NAFLD for the prediction of liver‐related death. (ClinicalTrials.gov number, NCT01927133).

Source:

Thursday, October 18, 2018

Fentanyl test strips prove useful in preventing overdoses

Fentanyl test strips prove useful in preventing overdoses
October 18, 2018
Mollie Rappe 

A Brown University study found that many young adults who tried fentanyl test strips reduced overdose risk by using less, going slower or using with someone else present.

PROVIDENCE, R.I. [Brown University] — Among more than 72,000 deaths in the U.S. last year, fentanyl — a highly potent prescription opioid often used to lace other heroin or cocaine, but hard for drug users to detect — factored into many of cases.

In the search for solutions, a team of researchers led by Brandon Marshall, an associate professor of epidemiology at Brown University’s School of Public Health, provided rapid-acting fentanyl test strips to young adults at risk of overdose in the state. New research by the team found that most of those young adults used the strips — and many who detected fentanyl reported changing their behavior to reduce overdose risk.

“We found that fentanyl test strips are an effective harm-reduction tool to prevent overdose,” Marshall said. “Harm reduction is important because everyone deserves to be able to take care of themselves and make informed decisions about their health, whether they use drugs or not. These tests strips could be a life-saving intervention for many young adults who use drugs.”

The findings were published on Thursday, Oct. 18, in the International Journal of Drug Policy.

The fentanyl test strips work like an over-the-counter pregnancy test, said Max Krieger, a research assistant in Marshall’s lab and the lead author of the study. Each single-use strip is dipped into water containing a bit of drug residue, and after a minute, either one or two red lines appear — one line means the liquid contains fentanyl, and two lines means the test did not detect the drug.


In this pilot study, the researchers provided test strips to 93 young adults who reported injecting opioids or using heroin, cocaine or prescription pills bought off the streets in the past month, and taught them how to use the strips.

Each participant received 10 strips,which cost about $1 each but aren’t commercially available. The study found that 77 percent of them used at least one test strip. Of the participants who used the strips, 12 percent used all 10 strips, and about half gave strips to friends. All participants also received overdose prevention education and a naloxone kit — commonly known by the brand name Narcan — to take home.

Half of the participants who used the strips detected fentanyl in their drug supply. Of those, 45 percent reported using smaller amounts, 42 percent proceeded more slowly when using, and 39 percent used with someone else present, who could call 911 or administer naloxone in the case of overdose. Some participants used multiple overdose-reducing strategies, and a few reported discarding fentanyl-laced drugs, Marshall said.

“Our study shows that the fentanyl test strips are effective at preventing overdoses,” Krieger said. “A majority of our participants who received a positive result changed their drug-using behavior. The harm reduction concept behind these test strips, adding a cheap but effective layer of protection against known overdose risks, is similar to other health precautions such as using condoms to prevent sexually transmitted diseases.”

Almost all of the participants (98 percent) — even those who didn’t use a single strip — said they were confident in their ability to use the strips, and 95 percent wanted to continue using them.

The study also found that participants would feel most comfortable obtaining rapid-acting fentanyl test strips at health clinics and other community-based organizations. The authors suggest that “community-based organizations that conduct overdose prevention education and outreach efforts may be ideal venues for rapid fentanyl test strip training and distribution, as these organizations also distribute other harm reduction supplies.”

Marshall cautioned that the findings might not apply to older drug users. The average age of the participants was 27.

The research team is analyzing the results from in-depth interviews with participants to learn more about their overdose risks and how they used the fentanyl test strips to avoid overdose, Marshall said. He hopes to build from this pilot study and conduct a larger efficacy trial to assess the effectiveness of the test strips in reducing overdoses in a larger population.

In addition to Krieger and Marshall, the research team included William Goedel, Dr. Josiah Rich and Traci Green of Brown; Jane Buxton and Dr. Mark Lysyshyn of the University of British Columbia; Dr. Edward Bernstein and Dr. Scott Hadland of the Grayken Center for Addiction, Boston University School of Medicine; and Susan Sherman of Johns Hopkins University’s Bloomberg School of Public
Health.

Funding from Brown’s Office of the Vice President of Research supported the pilot study.

https://news.brown.edu/articles/2018/10/fentanyl

Wednesday, October 17, 2018

Effect of cannabis use on chronic liver disease from Hepatitis C Virus infection

In The Media
Marijuana Use May Improve Cirrhosis Risk in Patients With Hepatitis C
Kenneth Bender, PharmD, MA
Publish Date: Wednesday, October 17, 2018
In an observation of a large pool of patients with hepatitis C virus (HCV), cannabis users had a lower prevalence of liver cirrhosis, more favorable health status at hospital discharge, and lower total health care costs than non-users.
Read the article...

In The Journal 
Canadian Journal of Gastroenterology and Hepatology
Volume 2018, Article ID 9430953, 9 pages
https://doi.org/10.1155/2018/9430953

Research Article
Reduced Incidence and Better Liver Disease Outcomes among Chronic HCV Infected Patients Who Consume Cannabis
Received 1 May 2018; Revised 13 August 2018; Accepted 29 August 2018; Published 23 September 2018

Abstract
Background and Aim. The effect of cannabis use on chronic liver disease (CLD) from Hepatitis C Virus (HCV) infection, the most common cause of CLD, has been controversial. Here, we investigated the impact of cannabis use on the prevalence of CLD among HCV infected individuals. Methods. We analyzed hospital discharge records of adults (age ≥ 18 years) with a positive HCV diagnosis. We evaluated records from 2007 to 2014 of the Nationwide Inpatient Sample (NIS). We excluded records with other causes of chronic liver diseases (alcohol, hemochromatosis, NAFLD, PBC, HBV, etc.). Of the 188,333 records, we matched cannabis users to nonusers on 1:1 ratio (4,728:4,728), using a propensity-based matching system, with a stringent algorithm. We then used conditional regression models with generalized estimating equations to measure the adjusted prevalence rate ratio (aPRR) for having liver cirrhosis (and its complications), carcinoma, mortality, discharge disposition, and the adjusted mean ratio (aMR) of total hospital cost and length of stay (LOS) [SAS 9.4]. Results. Our study revealed that cannabis users (CUs) had decreased prevalence of liver cirrhosis (aPRR: 0.81[0.72-0.91]), unfavorable discharge disposition (0.87[0.78-0.96]), and lower total health care cost ($39,642[36,220-43,387] versus $45,566[$42,244-$49,150]), compared to noncannabis users (NCUs). However, there was no difference among CUs and NCUs on the incidence of liver carcinoma (0.79[0.55-1.13]), in-hospital mortality (0.84[0.60-1.17]), and LOS (5.58[5.10-6.09] versus 5.66[5.25-6.01]). Among CUs, dependent cannabis use was associated with lower prevalence of liver cirrhosis, compared to nondependent use (0.62[0.41-0.93]). Conclusions. Our findings suggest that cannabis use is associated with decreased incidence of liver cirrhosis, but no change in mortality nor LOS among HCV patients. These novel observations warrant further molecular mechanistic studies.

Combination immunotherapy may increase liver injury risk

Combination immunotherapy may increase liver injury risk
October 17, 2018
PHILADELPHIA – Patients who received treatment with multiple immunotherapy drugs had increased risks for drug-induced liver injury compared with single therapy courses, as presented at the American College of Gastroenterology Annual Meeting.

“This is a rather new subsection of drug-induced liver injury that has come to our attention since the advent of immunotherapy drugs in the treatment of various different cancers, ranging from metastatic melanoma ... to colorectal cancer and renal cell carcinoma,” Vivek Bose, MD, from the Rutgers Robert Wood Johnson Medical Group in New Jersey, said during his presentation. 

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See more from American College of Gastroenterology Annual Meeting

Shortened Therapy of Eight Weeks With Paritaprevir/ritonavir/Ombitasvir and Dasabuvir Is Highly Effective in People With Recent HCV Genotype 1 Infection

Is an 8-week therapy of paritaprevir/ritonavir/ombitasvir and dasabuvir + ribavirin as effective as the standard 12-week regimen in individuals with recent HCV infection?

October 17, 2018 
Articles Available on Medscape 
J Viral Hepat. 2018;25(10):1180-1188. 
and dasabuvir

Abstract 
Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12 weeks are approved for treatment of chronic HCV genotype 1 infection. This study assessed the efficacy of shortened duration paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 8 weeks among people with recent HCV infection. In this open-label single-arm trial conducted in Australia, England and New Zealand, adults with recent HCV (duration of infection <12 months) received paritaprevir/ritonavir/ombitasvir and dasabuvir (with weight-based ribavirin for genotypes 1a and 1, no subtype) for 8 weeks. The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) population. Thirty people (median age 38 years, male 93%) commenced treatment (with ribavirin, 97%), of whom 77% (n = 23) were HIV-positive, 93% (n = 28) had genotype 1a infection and 53% (n = 16) had ever injected drugs. Median maximum ALT in the preceding 12 months was 433 IU/L (IQR 321, 1012). Acute clinical hepatitis with ALT > 10 x ULN was documented in 83% (n = 25); one participant (3%) had jaundice. At baseline, median estimated duration of infection was 30 weeks (range 11, 51), and median HCV RNA was 5.7 log10 IU/mL (range 2.7, 7.3). SVR12 was achieved in 97% (29/30; early discontinuation at week 2, n = 1; per protocol 100%, 29/29). No relapse or reinfection was observed. In conclusion, paritaprevir/ritonavir/ombitasvir and dasabuvir (with ribavirin) for eight weeks were highly effective among HIV-positive and HIV-negative individuals with recent HCV infection. These data support the use of this shortened duration direct-acting antiviral regimen in this population.

Read the full-text articlehttp://www.medscape.com/viewarticle/902923

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UC researchers support universal screening to tackle rise in hepatitis C

Recommended Reading
At-Risk Teens and Young Adults Overlooked During Opioid Crisis Too Few Tested for Hepatitis C, Research Suggests
SAN FRANCISCO – Teens and young adults who have injected drugs are at risk for contracting hepatitis C, but most aren’t tested and therefore don’t receive life-saving treatment, according to a national study being presented at IDWeek 2018. The study of more than 250,000 at-risk youth found only one-third of those with diagnosed opioid use disorder (OUD) were tested for hepatitis C...
Read more...

UC researchers support universal screening to tackle rise in hepatitis C 
Physicians are encountering a growing number of younger patients who are testing positive for hepatitis C virus (HCV) fueled largely by the opioid crisis impacting communities around the country. That increase and more effective and tolerable drug regimens for HCV infection, means one-time universal screening of all adults for HCV is now cost effective and recommended, say physician researchers in the University of Cincinnati (UC) College of Medicine.

The researchers used a computerized Markov state transition model to estimate the impact of one-time universal screening of adults 18 years of age and older compared either with no screening at all or with the current guideline-based strategy of largely screening baby boomers—adults born between 1945 and 1965—for HCV, says Mark Eckman, MD, Posey Professor of Clinical Medicine and Director of UC Division of General Internal Medicine.

They measured effectiveness with quality-adjusted life years (QALYs)—that’s the gain of in life expectancy adjusted for the quality of life—and costs from the health system perspective in 2017 U.S. dollars, says Eckman, lead author of the study and a UC Health physician. Universal screening followed by guideline-based treatment of all those with chronic HCV infection has an incremental cost effectiveness ratio of $11,378 per quality-adjusted life year compared with birth cohort-based screening alone.

"Most health economists consider anything less than $50,000 per quality-adjusted life year to be highly cost-effective,” says Eckman.

The results of the study are available online in the scholarly journal Clinical Gastroenterology and Hepatology.

The Centers for Disease Control and Prevention (CDC) estimates 2.7 million individuals in the U.S. have chronic HCV infection with 81 percent of that group consisting of baby boomer adults. In 2011, in addition to testing individuals at high risk due to intravenous drug use or other possible exposures to HCV, the CDC recommended one-time testing for the baby boomer cohort. That recommendation was later endorsed by the U.S. Preventive Services Task Force.

But since then the face and treatment of hepatitis C has changed.

"So what happened to make it reasonable to screen a wider population for HCV?” asks Eckman. "The incidence of hepatitis C among younger drug-injecting patients is skyrocketing so we have a blip in HCV cases that’s no longer isolated to the baby boomer cohort.

"We are also now in an era of HCV treatments that are more effective than even five or six years ago. Furthermore, these new regimens are easier to tolerate, have fewer severe side effects and require a short period of treatment,” says Eckman.

"All these factors coming together are what drove the model to show that screening a broader population than just the baby boomer cohort is effective,” says Eckman.

The baby boomer generation came of age during a time of experimentation, and many individuals who may have tried injectable drugs, even once, and never thought of themselves as having a problem, may be infected with the hepatitis C virus, says Eckman. "While these silent cases have been hanging out for decades what has changed recently is the new epidemic of hepatitis C in younger patients related to drug use,” he says.

Eckman says the cost to treat HCV can range from $9,000 to $30,000 per month depending on the medications being used, and that many health insurance plans, including Medicare Part D and most Medicaid plans cover the costs of treatment. For individuals without health insurance, treatment may remain a challenge, he adds.

Eckman says the U.S. Preventive Services Task Force is currently reviewing and updating guidelines for hepatitis C and it’s possible a broadening of the current screening recommendations may occur.

"Early diagnosis and treatment of hepatitis C infection prevents development of progressive liver disease, and reduces long-term risk of cirrhosis, liver cancer and other HCV-associated health problems”, says study co-author and liver expert, Kenneth Sherman, MD, PhD, Gould Professor of Medicine and Director in the UC Division of Digestive Diseases.


John Ward, MD from the Task Force for Global Health and the Centers for Disease Control and Prevention is also a co-author of the study. Funding for the study came from the CDC Foundation along with support coming from multiple donors to the CDC Foundation’s Viral Hepatitis Action Coalition.

Sherman has grants/contracts (institutional funding) from AbbVie, Bristol-Myers Squibb, Gilead, Inovio, Intercept, MedImmune, and Merck, and serves on advisory boards for Abbott Laboratories, Gilead, MedImmune, Merck, and Inovio. Sherman also serves on safety monitoring boards for Watermark and MedPace. Eckman has grant support from Merck through the Merck Investigator Studies Program.

Monday, October 15, 2018

Liver Cancer Treatment Paradigm Undergoing Major Overhaul

Liver Cancer Treatment Paradigm Undergoing Major Overhaul
Christine Lehmann, MA
Published Online: Oct 15,2018

Until recently, few systemic therapies had been approved for the treatment of patients with liver cancer, as few agents could demonstrate significant benefit over placebo. Sorafenib (Nexavar) was the first systemic therapy that extended median overall survival (OS) over placebo by nearly 3 months (10.7 versus 7.9 months),1 and, in December 2007, it became the first systemic therapy approved by the FDA for patients with unresectable hepatocellular carcinoma (HCC).

Read the article: