Wednesday, May 30, 2018

FDA Accepts Supplemental New Drug Application for Cabozantinib in Advanced HCC

Exelixis Announces U.S. FDA Accepts Supplemental New Drug Application for CABOMETYX® (cabozantinib) in Previously Treated Advanced Hepatocellular Carcinoma

– U.S. Food and Drug Administration assigns Prescription Drug User Fee Act action date of January 14, 2019 –

– The supplemental New Drug Application is based on the CELESTIAL phase 3 pivotal trial, in which CABOMETYX provided a statistically significant and clinically meaningful improvement versus placebo in overall survival –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--May 29, 2018-- Exelixis, Inc. (Nasdaq:EXEL) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the company’s supplemental New Drug Application (sNDA) for CABOMETYX® (cabozantinib) tablets as a treatment for patients with previously treated advanced hepatocellular carcinoma (HCC). The FDA has completed its filing review and has determined that the application is sufficiently complete to permit a substantive review. The filing has been assigned a Prescription Drug User Fee Act (PDUFA) action date of January 14, 2019.

“Patients with this aggressive form of advanced liver cancer urgently need new treatment options after they progress on first-line therapy,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “The acceptance of our sNDA filing for CABOMETYX is a critical step forward as we work to help address this unmet need, and we intend to work closely with the FDA as they review the application.”

An sNDA is an application to the FDA that, if approved, will allow a drug sponsor to make changes to a previously approved product label, including modifications to the indication. Exelixis announced they submitted the sNDA for the treatment of previously treated advanced HCC to the FDA in March 2018 based on results from the CELESTIAL phase 3 pivotal trial of CABOMETYX in patients with advanced HCC who received prior sorafenib.

About the CELESTIAL Study
CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is overall survival, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

In October 2017, Exelixis announced that the independent data monitoring committee for the CELESTIAL study recommended that the trial be stopped for efficacy following review at the second planned interim analysis, with cabozantinib providing a statistically significant and clinically meaningful improvement in overall survival compared with placebo in patients with previously treated advanced HCC. In March 2017, the FDA granted orphan drug designation to cabozantinib for the treatment of advanced HCC.

Please see Important Safety Information below and full U.S. prescribing information at

Hepatitis A is usually not a problem to recover from. But in Michigan, 27 people died since this outbreak began.

USA Today Network
May 29, 2018
Kristen Jordan Shamus, Detroit Free Press

Hepatitis A is usually not a problem to recover from. But in Michigan, 27 people died since this outbreak began.
WARREN, Mich.— Michigan is in the throes of the largest hepatitis A outbreak in the USA, a flareup that began in August 2016 and has killed 27 people, state health officials say.

The hepatitis A virus, which attacks the liver, is highly contagious. Just ask Christopher Larime ,46, of Grosse Pointe Park, who goes out to lunch most days with co-workers from the General Motors Tech Center here.
Read the article: 

May 29, 2018

Prospective Study: No psychiatric side effects with new IFN-free treatment for HCV

BMC Psychiatry
Direct-acting antiviral treatment in real world patients with hepatitis C not associated with psychiatric side effects: a prospective observational study
Isak Sundberg, Anders Lannergård, Mia Ramklint and Janet L. Cunningham

BMC Psychiatry 2018
Received: 26 September 2017
Accepted: 11 May 2018
Published: 29 May 2018

Treatment of Hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based treatments to direct-acting antivirals (DAAs). Patients with HCV have an elevated psychiatric morbidity (including substance abuse) and patients with such comorbidity have often been excluded from treatment with IFN. To date, little is known about psychiatric adverse effects of DAA-based regimens. We therefore aimed to study the psychiatric side effects of new IFN-free treatment for HCV (including depressive symptoms and sleep) in real world patients also including those with a history of psychiatric diagnosis, substance abuse or drug dependence.

Consecutive patients were monitored during treatment with three of the latest DAA agents (sofosbuvir, simeprevir and daclatasvir). Repeated expert psychiatric assessments from baseline to 12 weeks post-treatment were performed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) clinical version and the self-report versions of the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Pittsburgh Sleep Quality Index (PSQI). Friedman’s test was performed to calculate differences in the MADRS-S and PSQI over time. In a post-hoc analysis Wilcoxon’s test was used to compare baseline depressive symptoms with those at post-treatment. Spearman’s rank correlation test was conducted in another post-hoc analysis to evaluate the correlation between symptoms of depression and HCV viral load at baseline.

At baseline, 15/17 patients (88%) had a history of any psychiatric diagnosis; 11 (65%) had a history of substance abuse or dependence; and 11 (65%) had previously been treated with IFN and six of those had experienced psychiatric side effects. There was no correlation between depressive symptoms and HCV viral load at baseline. Symptoms of depression did not increase during DAA treatment and were lower 12 weeks post-treatment compared with baseline: MADRS-S 10.7 vs. 8.3 (p = 0.01). This observation held when excluding patients taking antidepressant medication. Sleep quality did not significantly change during treatment. Adherence to treatment was estimated to 95% and sustained virological response was 88%.

Despite high psychiatric morbidity, including previous substance abuse, patients successfully completed DAA treatment without increasing depressive symptoms or sleep disturbance. Symptoms of depression were significantly reduced 12 weeks after DAA treatment.

Hepatitis C virus Direct-acting antiviral Depression Sleep Side effects

Read the full article ›

China Drug Administration Approves Epclusa® (Sofosbuvir/Velpatasvir)

China Drug Administration Approves Epclusa® (Sofosbuvir/Velpatasvir), Gilead's Pan-Genotypic Treatment for Chronic Hepatitis C Virus Infection

- Epclusa is the First Approved Pan-Genotypic Once Daily Single Table Regimen for Chronic Hepatitis C Virus Infection in China -

FOSTER CITY, Calif.--(BUSINESS WIRE)--May 30, 2018-- Gilead Sciences, Inc. (NASDAQ: GILD) announced today that the China Drug Administration (CDA) has approved Epclusa® (sofosbuvir 400 mg/velpatasvir 100 mg) for the treatment of adults with genotype 1-6 chronic hepatitis C virus (HCV) infection. The CDA also approved Epclusa in combination with ribavirin (RBV) for adults with HCV and decompensated cirrhosis. Epclusa is the first pan-genotypic HCV single tablet regimen (STR) approved in China.

The approval of Epclusa in China is supported by five international Phase 3 studies, ASTRAL-1, ASTRAL-2, ASTRAL-3, ASTRAL-4 and ASTRAL-5. High overall rates of SVR12 (defined as undetectable HCV RNA 12 weeks after completing therapy), ranging from 92-100 percent, were achieved across difficult-to-cure patient populations including treatment-experienced patients and those with compensated or decompensated cirrhosis.

"The safety and efficacy profile of Epclusa are supported by large clinical and real-world global datasets," said Professor Lai Wei, Peking University People's Hospital and Institute of Hepatology, Peking University. "With high cure rates across all HCV genotypes, Epclusa could increase HCV treatment in China by potentially eliminating the need for genotype testing, which can be a barrier to treatment in many settings."

HCV is the fourth-most commonly reported infectious disease in China, with approximately 10 million people infected. HCV genotypes 1, 2, 3 and 6 account for more than 96 percent of all cases.

In the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,035 treatment-naïve and treatment-experienced patients with genotype 1-6 HCV infection, without cirrhosis or with compensated cirrhosis, received 12 weeks of Epclusa. Ninety-eight percent (1,015/1,035) of patients achieved SVR12. In the ASTRAL-5 study, 106 treatment-naïve and treatment-experienced patients with genotype 1-6 HCV infection, without cirrhosis or with compensated cirrhosis, who were coinfected with HIV and on a stable antiretroviral therapy, received 12 weeks of Epclusa. Ninety-five percent (101/106) of patients achieved SVR12.

The ASTRAL-4 study assessed the safety and efficacy of 12 weeks of Epclusa with or without RBV or 24 weeks of Epclusa in 267 HCV-infected patients with genotypes 1-4 and 6 decompensated cirrhosis (Child-Pugh B). Patients with decompensated cirrhosis receiving Epclusa with RBV for 12 weeks achieved 94 percent (82/87) SVR12.

The most common adverse reactions (=10 percent) experienced by patients treated with Epclusa in ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-5 were headache and fatigue. The placebo-treated patients in the ASTRAL-1 experienced headache and fatigue at a similar frequency. The most common adverse reactions (=10 percent) experienced by HCV-infected patients with decompensated cirrhosis treated with Epclusa and RBV in ASTRAL-4 were fatigue, anemia, nausea, headache, diarrhea and insomnia. Four patients treated with Epclusa with RBV, discontinued treatment due to adverse events.

"As the first once-daily, interferon-free single tablet regimen for HCV patients regardless of genotype, Epclusa offers physicians in China an important new option for effectively treating their patients while potentially helping to reduce the significant burden of HCV at a population level," said John F. Milligan, PhD, Gilead's President and Chief Executive Officer. "Gilead has now launched two direct-acting antiviral treatments in China, and we are committed to supporting efforts to screen and link patients to treatment, to help address the country's HCV epidemic."

Epclusa received marketing approval from the U.S. Food and Drug Administration (FDA) and the European Commission in 2016 as the first pan-genotypic STR for HCV infection. It is also approved for use in 54 countries.

Sovaldi (sofosbuvir) as a single agent received marketing approval from the China Food and Drug Administration in 2017 for the treatment of adults infected with HCV genotype 1, 2, 3, 4, 5 or 6 and for adolescents (aged 12 to 18 years) with HCV genotype 2 or 3, as a component of a combination antiviral treatment regimen.

Tuesday, May 29, 2018

Can anti-viral therapy reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus

Available on Medscape
Viral Eradication Reduces Both Liver Stiffness and Steatosis in Patients With Chronic Hepatitis C Virus Infection Who Received Direct-acting Anti-viral Therapy
In this study, we investigated changes in liver stiffness and steatosis as determined by MRI in patients with chronic HCV genotype 1 or 2 infection who received direct-acting anti-viral therapy and achieved SVR.
May 29, 2018 

Viral Eradication Reduces Both Liver Stiffness and Steatosis in Patients With Chronic Hepatitis C Virus Infection Who Received Direct-acting Anti-viral Therapy
T. Tada; T. Kumada; H. Toyoda; Y. Sone; K. Takeshima; S. Ogawa; T. Goto; A. Wakahata; M. Nakashima; M. Nakamuta; J. Tanaka

Background Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear.

Aims To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR).

Methods A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24).

Results Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70–4.18) kPa and 2.80 (2.40–3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7–3.4)% and 1.9 (1.3–2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24.

Conclusion Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020).

Novel Medicaid Strategy Proposed to Increase Access to HCV Treatment

Infectious Disease Advisor
Novel Medicaid Strategy Proposed to Increase Access to HCV Treatment
Zahra Masoud
Implementing a novel drug purchasing strategy may dramatically increase access to drugs for hepatitis C virus (HCV) infection for patients enrolled in Medicaid without increasing state and federal costs, according to a study recently published in the Annals of Internal Medicine.

Although the annual HCV-related death toll in the United States exceeds that of a combination of HIV and 59 other infectious diseases, curative treatments introduced in 2013 resulted in sustained virologic response that has been associated with lower mortality in individuals with chronic HCV infection.

Read More:

New At Infectious Disease Advisor
Does Substance Use Disorder Affect Sustained Virologic Response to DAAs?
Infectious Disease Advisor
Although hepatitis C virus (HCV) treatment adherence is worse in patients with comorbid substance use disorders, sustained virologic response (SVR) to …

Most popular vitamin and mineral supplements provide no health benefit, study finds

Most popular vitamin and mineral supplements provide no health benefit, study finds
May 28, 2018, St. Michael's Hospital 

The most commonly consumed vitamin and mineral supplements provide no consistent health benefit or harm, suggests a new study led by researchers at St. Michael's Hospital and the University of Toronto

Published today in the Journal of the American College of Cardiology, the systematic review of existing data and single randomized control trials published in English from January 2012 to October 2017 found that multivitamins, vitamin D, calcium and vitamin C—the most common supplements—showed no advantage or added risk in the prevention of cardiovascular disease, heart attack, stroke or premature death. Generally, vitamin and mineral supplements are taken to add to nutrients that are found in food.

"We were surprised to find so few positive effects of the most common supplements that people consume," said Dr. David Jenkins, the study's lead author. "Our review found that if you want to use multivitamins, vitamin D, calcium or vitamin C, it does no harm—but there is no apparent advantage either."

The study found folic acid alone and B-vitamins with folic acid may reduce cardiovascular disease and stroke. Meanwhile, niacin and antioxidants showed a very small effect that might signify an increased risk of death from any cause.

"These findings suggest that people should be conscious of the supplements they're taking and ensure they're applicable to the specific vitamin or mineral deficiencies they have been advised of by their healthcare provider," Dr. Jenkins said.

His team reviewed supplement data that included A, B1, B2, B3 (niacin), B6, B9 (folic acid), C, D and E; and β-carotene; calcium; iron; zinc; magnesium; and selenium. The term 'multivitamin' in this review was used to describe supplements that include most vitamins and minerals, rather than a select few.

"In the absence of significant positive data—apart from folic acid's potential reduction in the risk of stroke and heart disease—it's most beneficial to rely on a healthy diet to get your fill of vitamins and minerals," Dr. Jenkins said. "So far, no research on supplements has shown us anything better than healthy servings of less processed plant foods including vegetables, fruits and nuts." 

Journal of the American College of Cardiology

Monday, May 28, 2018

Canada launches call for proposals under its Harm Reduction Fund

Government of Canada launches call for proposals under its Harm Reduction Fund
Reducing the risk of HIV, hepatitis C and other blood-borne infections

OTTAWA, May 28, 2018 /CNW/ - Sexually transmitted and blood-borne infections, including HIV and hepatitis C, are largely preventable but remain a significant public health concern in Canada. The Government of Canada is taking action to reduce transmission of these diseases, including measures to prevent the spread of HIV and hepatitis C through the sharing of drug-use equipment, such as needles and pipes.

Through its Harm Reduction Fund, the Public Health Agency of Canada is investing $30 million over five years to support community initiatives to address the risk of infection among people who share drug-use equipment.

Today, the Honourable Ginette Petitpas Taylor, Minister of Health, launched an open call for proposals to support community projects that will reduce the rate of infections of HIV and hepatitis C among people who share injection and other drug-use equipment. Successful projects will implement evidence-based, time-limited interventions such as the development of educational resources for people who use drugs, peer outreach initiatives and training for health service providers.

The open call for proposals will allow applicants to apply for up to three years of funding for time-limited projects.

"The Harm Reduction Fund will help organizations implement response activities in communities where there are high rates of infections among people who share drug-use equipment, with the goal of reducing the rates of diseases, like HIV and hepatitis C, across our country."

The Honourable Ginette Petitpas Taylor, P.C., M.P.
Minister of Health

"Evidence shows that harm reduction is a vital part of a comprehensive, compassionate and collaborative public health approach to prevent the transmission of infectious diseases that result from the sharing of drug-use equipment. The Harm Reduction Fund will help Canadians who use drugs to adopt safer behaviours, and will reduce the rate of preventable diseases like HIV and hepatitis C."

Dr. Theresa Tam
Chief Public Health Officer of Canada

Quick Facts
Eligible activities under the Harm Reduction Fund include front-line prevention activities and capacity-building of individuals, providers and systems.
Additional calls for project proposals are planned for spring 2019 and 2020.
People who share drug-use equipment continue to be disproportionately represented among those acquiring HIV and hepatitis C infections in Canada.
In 2014, 10.5% of new HIV infections were among people who injected drugs.
68% of people who inject drugs and who were surveyed between 2010 and 2012 indicated that they had at one point been infected with hepatitis C.

Associated Links
Harm Reduction Fund
Canadian Drugs and Substances Strategy

SOURCE Public Health Agency of Canada

Saturday, May 26, 2018

Weekend Video: HCV From Screening to Cure - Hosted By Ira M. Jacobson, MD.

Good day folks, the following video presentation; "HCV From Screening to Cure: A Closer Look at Changing At-Risk Populations and an Evolving Treatment Landscape" with Ira M. Jacobson, MD., and provided by Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education, is now available for your viewing pleasure.

In this learning activity the good doctor will discuss screening strategies, stigma, patient-related barriers to treatment, hepatitis C testing for identifying current infection, and tests used to stage fibrosis. Also discussed is treatment for HCV patients with cirrhosis, as well as treatment adherence, duration, treatment according to HCV genotype, ending with "How Much Care Do The Cured Need?"

Although the learning activity is aimed at HCV specialists, this short patient-friendly presentation is beneficial for anyone considering HCV testing and treatment.

PeerView CME
Published on May 25, 2018
Released April 30, 2018
Ira M. Jacobson, MD, discusses hepatitis C virus in this CME/CE activity titled "HCV From Screening to Cure: A Closer Look at Changing At-Risk Populations and an Evolving Treatment Landscape." For the full presentation and infographics, complete CME/CE information, and to apply for credit, please visit us at CME/CE credit will be available until April 29, 2019.

This CME/CE activity is jointly provided by Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education.

Quick blood test can detect liver damage before symptoms appear

UMass Amherst Chemists, International Team Develop New Blood Test to Detect Liver Damage in Under an Hour 
May 24, 2018
Vincent Rotello

AMHERST, Mass. – Chemist Vincent Rotello at the University of Massachusetts Amherst, with colleagues at University College London (UCL), U.K., announce today that they have developed a “quick and robust” blood test that can detect liver damage before symptoms appear, offering what they hope is a significant advance in early detection of liver disease. Details appear in Advanced Materials.

Their new method can detect liver fibrosis, the first stage of liver scarring that can lead to fatal disease if left unchecked, from a blood sample in 30-45 minutes, the authors note. They point out that liver disease is a leading cause of premature mortality in the United States and U.K., and is rising. It often goes unnoticed until late stages of the disease when the damage is irreversible.

For this work, Rotello and his team at UMass Amherst’s Institute of Applied Life Sciences (IALS) designed a sensor that uses polymers coated with fluorescent dyes that bind to blood proteins based on their chemical processes. The dyes change in brightness and color, offering a different signature or blood protein pattern.

He says, “This platform provides a simple and inexpensive way of diagnosing disease with potential for both personal health monitoring and applications in developing parts of the world.” Rotello and colleagues hope the new test can be used routinely in medical offices, clinics and hospitals to screen people with elevated liver disease risk so they can be treated “before it’s too late.”

The UCL team tested the sensor by comparing results from small blood samples equivalent to finger-prick checks from 65 people, in three balanced groups of healthy patients and among those with early-stage and late-stage fibrosis. This was determined using the Enhanced Liver Fibrosis (ELF) test, the existing benchmark for liver fibrosis detection. They found that the sensor identified different protein-level patterns in the blood of people in the three groups. The ELF test requires samples to be sent away to a lab.

Co-author William Peveler, a chemist now at the University of Glasgow, adds, “By comparing the different samples, the sensor array identified a ‘fingerprint’ of liver damage. It’s the first time this approach has been validated in something as complex as blood, to detect something as important as liver disease.”

The investigators report that the test distinguished fibrotic samples from healthy blood 80 percent of the time, reaching the standard threshold of clinical relevance on a widely-used metric and comparable to existing methods of diagnosing and monitoring fibrosis. The test distinguished between mild-moderate fibrosis and severe fibrosis 60 percent of the time. The researchers plan further tests with larger samples to refine the method’s effectiveness.

Peter Reinhart, director of UMass Amherst’s IALS says, “These exciting findings epitomize the mission of IALS to translate excellent basic science into diagnostics, therapeutic candidates and personalized health monitoring devices to improve human health and well-being.”

Peveler adds, “This may open the door to a cost-effective regular screening program thanks to its simplicity, low cost and robustness. We’re addressing a vital need for point-of-care diagnostics and monitoring, which could help millions of people access the care they need to prevent fatal liver disease.”

Rotello explains that the sensing strategy uses a “signature-based” approach that is highly versatile and should be useful in other areas. “A key feature of this sensing strategy is that it is not disease-specific, so it is applicable to a wide spectrum of conditions, which opens up the possibility of diagnostic systems that can track health status, providing both disease detection and monitoring wellness.”

In addition to UMass Amherst, UCL and the University of Glasgow, the U.K.-based research and development firm iQur Ltd. took part in the study. The work was supported by the U.K. Royal Society, the U.K. Engineering and Physical Sciences Research Council, the U.S. National Institutes of Health and the U.K. National Institute for Health Research UCLH Biomedical Research Centre.

Advanced Materials article

Friday, May 25, 2018

UK - Increasing treatment uptake to eradicate hepatitis C infection

Nursing Times [online]; 114: 6, 38-42.
Increasing treatment uptake to eradicate hepatitis C infection
Gemma Botterill
25 May, 2018

Full Article:
View Online

Viral hepatitis is a major cause of death across the world and hepatitis C virus infection represents a large share of the burden. Curing hepatitis C has become more feasible since the emergence of direct-acting antivirals, which have cure rates of >95%. NHS England has set up a national network of treatment services and, since February 2017, treatment has been available to all infected patients, regardless of genotype and liver fibrosis staging. Today the challenge is not so much how to treat patients, but how to identify them in the first place, as many are not known to health services. This is because they are unaware of their infection, they do not feel they need treatment, do not know about the new treatments available, or they belong to hard-to-reach groups such as homeless people, prisoners and injecting drug users. This article looks at the methods used at Queen Elizabeth Hospital Birmingham to re-engage with patients lost to follow-up and to engage with local drug users and prison inmates.

Extending DAA regimens
At the beginning of 2016, patients without cirrhosis became eligible for the new all-oral DAA regimens, except for genotype 3 patients, which led to many becoming disengaged from health services and lost to follow-up.

Finally, in February 2017, NHSE made DAA regimens available to all patients infected with HCV, regardless of genotype or liver fibrosis staging. The number of patients to treat in 2017/18 was increased by a quarter, with a corresponding increase in funding for the drugs, so 12,500 patients could be treated with an excellent chance of cure (Vine et al, 2015). The primary aim was to continue engaging with patients, particularly those without cirrhosis who could now be offered an all-oral treatment regimen (NHSE, 2016b).

Removing the Barriers from the Path to Eliminate Hepatitis C

Overcoming Barriers to Eliminate Hepatitis C

Happy Friday folks, hope you have some great plans for the upcoming holiday weekend!

If you get a chance check out this special issue on HCV elimination published in the June issue of Infectious Disease Clinics Of North America.

For your reading pleasure a few open access articles: 

Removing the Barriers from the Path to Eliminate Hepatitis C
Camilla S. Graham, Stacey B. Trooskin
Published in issue: June 2018

New Treatments Have Changed the Game: Hepatitis C Treatment in Primary Care
Shelley N. Facente, Katie Burk, Kelly Eagen, Elise S. Mara, Aaron A. Smith, Colleen S. Lynch
Published in issue: June 2018

Hepatitis C Virus Diagnosis and the Holy Grail
Tanya L. Applegate, Emmanuel Fajardo, Jilian A. Sacks
Published in issue: June 2018

Begin here.....

HCV Guidance Updates Recommendations for Screening and Treating Key Populations

HCV Guidance Updates Recommendations for Screening and Treating Key Populations

05/24/2018 — a website developed by the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) to provide up-to-date guidance on the management of hepatitis C (HCV) — has updated several sections of the website to reflect new testing and management recommendations for pregnant women, people who inject drugs, men who have sex with men and people who are incarcerated.

“Today, hepatitis C is curable for over 95 percent of people who undergo treatment,” explain HCV Guidance Co-Chairs, Marc G. Ghany, MD, MHSc; Arthur Y. Kim, MD; Kristen M. Marks, MD; and Hugo E. Vargas, MD. “With the success of HCV treatments, the medical community must now shift our focus toward eliminating HCV as a public health problem. As a first step, our Panel has made new recommendations to re-emphasize the importance of testing key populations and treating virtually all patients with the virus. We feel these recommendations are in alignment with the 2016 World Health Organization and National Academies of Sciences, Engineering and Medicine (NASEM) goals of eliminating HCV infection by 2030.”

Universal screening for pregnant women
Drawing from recent studies highlighting a sharp increase of HCV-infected women giving birth in the United States between 2011-2014, and a lack of evidence that risk-factor-based testing is effective in identifying chronic HCV infection, the updated HCV Guidance recommends all pregnant women be tested for HCV infection, ideally at the start of their prenatal care.

By screening all pregnant women at the beginning of prenatal care, physicians will increase opportunities for education and referral and allow early testing and treatment for exposed infants. Treatment of women post-pregnancy will improve the health of women and ultimately prevent future HCV transmission.

Men who have sex with men
Several outbreaks of sexually transmitted HCV infection among HIV-infected men who have sex with men have been reported since 2000. Additionally, HCV incidence is increasing among HIV infected men who have sex with men.

With these things in mind, the Panel has made new recommendations that focus on sexually active adult and adolescent men who have sex with men who are HIV-infected, who are initiating pre-exposure prophylaxis (PrEP) for HIV, or who have been successfully treated or spontaneously cleared HCV infection.

For these men, the Guidance recommends:
• At least annual (or more often, based on risk) testing for HCV antibody for those who have never been exposed to the virus.
• HCV RNA testing for those who were treated or spontaneously cleared HCV infection.

People who inject drugs
To address the growing number of cases of HCV infection due to the opioid epidemic, the updated Guidance recommends annual HCV testing for people who inject drugs and have never been tested for the virus. The guidance also recommends annual testing for people who have previously tested negative for the virus but continue to use injection drugs and treatment for those who test positive.

Additionally, the Guidance recommends:
• Substance use disorder treatment programs and needle/syringe exchange programs should offer routine, opt-out HCV antibody testing with reflexive or immediate confirmatory RNA testing and connection to care for those who are infected.
• People who inject drugs should be counseled on measures to reduce risk of HCV transmission to others.
• People who inject drugs should be connected to harm reduction services when available, including needle/syringe service programs and substance use disorder treatment programs.

People in correctional institutions
Research has shown that HCV infection disproportionately affects people in correctional institutions. The updated Guidance recommends that jails and prisons should implement opt-out testing for incarcerated individuals.

The Guidance also recommends:
• Chronically infected people in jail settings should receive counseling about HCV infection and be connected to follow-up community health care for evaluation of liver disease and treatment upon release.
• Chronically infected people in prisons — and those whose jail sentences are sufficiently long enough to complete a total course of antiviral therapy — should receive antiviral therapy according to AASLD/IDSA Guidance while incarcerated. Upon release, these patients should be connected to community health care to monitor for HCV-related complications.
• To prevent HCV re-infection and reduce the risk of progression of HCV-associated liver disease, prisons should provide harm reduction and evidence-based treatment for underlying substance use disorders.
• Jails and prisons should facilitate continuation of HCV therapy for individuals on treatment at the time of incarceration.

May 24, 2018
New and updated: 
Management of HCV in MSM
The determinants of sexually transmitted incident HCV among HIV-positive men who have sex with men (MSM) have not been thoroughly characterized, but risk factors have been identified.

Visit for more information about these recommendations and to view other sections of the HCV Guidance.

Read More>>

NVHR Applauds New AASLD and IDSA Guidelines for Hepatitis C Screening and Treatment for At-Risk Populations
Updated Hepatitis C Recommendations Emphasize Screening for Key Populations and Treatment for All People Living with HCV

WASHINGTON, DC (May 25, 2018) – The National Viral Hepatitis Roundtable (NVHR), a national coalition working together to eliminate hepatitis B and C in the United States, today applauded the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) for updating their hepatitis C virus (HCV) screening and treatment recommendations to focus on eradicating HCV among key populations. The new guidelines focus on groups most at-risk for HCV, including pregnant women who previously were not regularly screened, people who inject drugs, men who have sex with men and individuals who are incarcerated.

Thursday, May 24, 2018

Hepatitis C Virus Infection Treatments to Be Discontinued:Technivie, Viekira XR and Simeprevir

In Case You Missed It

FDA Website:

Also discontinued:

Janssen Pharmaceuticals (New 05/23/2018)
Simeprevir Capsules
Status: Discontinuation

Viekira XR

Abbvie (New 05/22/2018)
Dasabuvir Sodium; Ombitasvir; Paritaprevir; Ritonavir (Viekira XR) Tablets
Status: Discontinuation
Estimated product availability until January 1, 2019.
The product discontinuation is voluntary and not related to product quality, safety or efficacy.

Abbvie (New 05/22/2018)
Ombitasvir; Paritaprevir; Ritonavir (Technivie) Tablets
Status: Discontinuation
Estimated product availability until January 1, 2019. The product discontinuation is voluntary and not related to product quality, safety or efficacy.

MPR > News > Two Hepatitis C Virus Infection Treatments to Be Discontinued
Da Hee Han, PharmD
May 24, 2018
Two Hepatitis C Virus Infection Treatments to Be Discontinued
Two hepatitis C virus (HCV) combination treatments, Technivie (ombitasvir, paritaprevir, ritonavir) and Viekira XR (dasabuvir sodium, ombitasvir, paritaprevir, ritonavir), have been discontinued by AbbVie, according to the Food and Drug Administration (FDA). The discontinuation is voluntary and is not related to product quality, safety or efficacy.
Read the article:

What causes chronic fatigue? What we know, don’t know and suspect

Recommended Reading
February 2017
Persistent Neuropsychiatric Impairment in HCV Patients Despite Clearance of the Virus?!
Many patients with HCV infection report disabling chronic fatigue--even after viral clearance. Might HCV be implicated in a virus infection-associated chronic fatigue syndrome?
Link To Article: 2017 full-text article is open access over at Medscape (free registration required), discussion only, here (no registration). Patients can also read an overview with commentary at Infectious Disease Advisor. Original article was published 9 February 2017 in Journal of Viral Hepatitis.

May 16, 2018
Do fatigue and quality of life improve after hepatitis C is cured?
Keith Alcorn
Published: 16 May 2018
Patient-reported outcomes such as fatigue, vitality and mental health improve substantially in the two years following hepatitis C cure for people with cirrhosis, but people with cirrhosis are less likely than others to experience rapid resolution of severe fatigue after successful hepatitis C treatment, according to two studies from the Center for Outcomes Research in Liver Diseases reported last month at the 2018 International Liver Congress in Paris.

Today's Article
What causes chronic fatigue? What we know, don’t know and suspect
Mark Guthridge 
Senior Research Fellow, Monash University 

Around 200,000 people in Australia suffer from a debilitating illness often branded with the unfortunate name of chronic fatigue syndrome (CFS). I say “unfortunate” because this implies patients are simply tired, run-down, burnt-out or overly stressed.

But myalgic encephalomyelitis, or ME/CFS as it is now more commonly called, is a serious and incapacitating disease that can have a devastating impact on a patient’s life. Symptoms include:

profound and unexplained fatigue for more than six months
memory or concentration difficulties
muscle pain (myalgia) and weakness
joint pain
sleep disturbances
flu-like symptoms
light headedness, palpitations, breathlessness
heightened sensitivity to light and sound
tender lymph nodes, sore throats
new sensitivities to food, medicines or chemicals.

Initially bewildered by their incapacitating fatigue, many ME/CFS patients continue trying to go about their daily lives. But such efforts come at a severe cost. Even small amounts of activity can trigger “crashes” called post-exertional malaise that worsen symptoms, sometimes for many days.

Simple activities such as showering, grocery shopping or meeting a friend for coffee become difficult, if not impossible. Sadly, for around 25% of patients, symptoms are so severe they remain bed-bound or house-bound, and suicide risk is elevated.

Most patients face a major challenge getting a diagnosis. One UK study found less than half of doctors were confident with the diagnosis or treatment of ME/CFS and more than 85% of patients go from doctor to doctor for over two years without a diagnosis.

What we know
The underlying causes of ME/CFS have proved difficult to pinpoint. For many patients, blood and pathology testing are entirely normal.

This has led some to suggest ME/CFS is a psychological condition. In 2011, the findings of a clinical trial suggested patients could recover through psychological therapy (cognitive behavioural therapy or CBT) and graded exercise therapy. These findings have fuelled debate as to whether ME/CFS might be a disease of the mind.

But a landmark US study examining nearly 10,000 research publications suggested otherwise, concluding that ME/CFS is a serious, chronic, complex and systemic disease.

Criticisms of psychological and exercise therapy for ME/CFS have been widespread, with over 50 published letters in leading scientific journals (BMJ, Journal of Health Psychology, Nature, Lancet) raising serious concerns about the robustness of the claims.

Australian guidelines continue to recommend exercise and CBT therapies despite the US Centers for Disease Control and Prevention discontinuing these recommendations.

While exercise can clearly benefit patients with a wide range of illnesses, physical activity can cause a rapid deterioration of symptoms in patients with ME/CFS.

What we don’t know
There are no laboratory tests available to categorically diagnose someone with ME/CFS. But Australian research is playing a leading role in the discovery of possible diagnostic markers. For example, inflammatory blood proteins such as activin B and interferon are increased in ME/CFS. Other studies have shown metabolic waste products from some gut bacteria accumulate in ME/CFS patients and so may also provide diagnostic information in the future.

Women are four times more likely to be diagnosed with ME/CFS than men, but the reason for this is unclear. Also, having a first-degree relative with ME/CFS more than doubles the risk of developing the disease, but the role of genetics is not known.

For some, the onset of symptoms is slow. In others, ME/CFS begins with infections causing glandular fever (infectious mononucleosis), respiratory or gastrointestinal illnesses.

While ME/CFS patients have immune disruptions and abnormal inflammatory responses, the underlying causes remain elusive. The vicious cycles of tissue damage typical of autoimmune diseases such as multiple sclerosis or lupus don’t seem to occur in ME/CFS.

One theory is that ME/CFS patients have a “chink” in their immunological armour, possibly leading to persistent “smouldering” infections and chronic inflammation.

But it’s remarkably difficult to find direct evidence for such ongoing infections in most ME/CFS patients. And antiviral drugs or antibiotics seem to have very modest activity in ME/CFS despite their life-saving activities in many other infectious diseases.

ME/CFS patients also have metabolic defects in the way energy is generated in their bodies - pointing to one reason why they rapidly succumb to muscle fatigue during exercise. But whether this metabolic defect is due to immune attack, chronic infection or some other cause is unknown.

With no approved treatments or cures for ME/CFS, more research is urgently needed. So far, clinical trials examining the effects of immunosuppressive drugs, antibody therapies, anti-viral drugs, attention deficit hyperactivity disorder therapies and anti-depressants have not led to major improvements.

Diets and nutritional supplements also seem to provide little help. While some dietary supplements involved in generating metabolic energy seem to improve some ME/CFS symptoms, larger and better studies are required.

A reboot of ME/CFS research is now underway. Sufferers are hopeful the recent establishment of a National Health and Medical Research Council ME/CFS Advisory Committee will reinvigorate Australian biomedical ME/CFS research to find new treatments and possibly a cure.
Read the original article.

Blood test may predict who is most at risk for diabetes

Blood test may predict who is most at risk for diabetes 
Lisa Rapaport
(Reuters Health) - Adding a test normally used for diabetes monitoring to employee wellness exams could identify people who don’t have the disease but are at high risk of developing it, a recent study suggests. Researchers examined data from two different types of blood sugar test for more than 34,000 participants in a U.S. employee wellness program who didn’t have diabetes. At the start of the study, they all also had fasting blood sugar in a healthy range.

Diabetes Care, online April 26, 2018
Dov Shiffman, Carmen H. Tong, Charles M. Rowland, James J. Devlin, James B. Meigs and Michael J. McPhaul
Diabetes Care 2018 Apr; dc172500.

Recommended reading
HCV-Infected Patients With Diabetes Improve With Direct-Acting Antiviral Therapy: Presented at AACE

Localized US Efforts to Eliminate Hepatitis C

Localized US Efforts to Eliminate Hepatitis C 

The following full-text article is available for download, shared by Henry E. Chang via twitter

Download Full Article:

Elimination of Hepatitis C Virus in Australia: Laying the Foundation

The following full-text article is available for download, shared by Henry E. Chang via twitter

Elimination of Hepatitis C Virus in Australia: Laying the Foundation
Gregory J. Dore BSc, MBBS, MPH, FRACP, PhD Behzad Hajarizadeh MD, MPH, PhD

The development of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection is one of the great advances in clinical medicine in recent decades. Involving simple (once daily oral dosing), tolerable, short duration (8–12weeks), and highly efficacious (cure rates of >95%) regimens, DAA therapy has the potential to markedly increase HCV treatment uptake and turn around the escalating global disease burden associated with chronic HCV infection.1 The transformative nature of DAA therapy underpinned the development of World Health Organization(WHO) goals to eliminate HCV as a public health threat, which include 80% of eligible patients treated, a 65% decrease in HCV-related mortality, and an 80% decrease in new HCV infections by 2030.

-Australia has laid the foundation for hepatitis C virus elimination within the next decade.
-Key aspects of this foundation include high levels of screening and diagnosis, unrestricted access to direct-acting antiviral therapy, a diverse range of models of care, and high coverage of harm reduction strategies.
-Key features include government risk-sharing arrangement with the pharmaceutical companies, minimal out-of-pocket cost, no restrictions based on liver disease stage or drug/ alcohol use, prescribing authorization for all registered medical practitioners; and retreatment is allowed.
-Although initial uptake of direct-acting antiviral therapy was high, more efforts are required to continue the momentum.
-An hepatitis C virus elimination monitoring and evaluation program is in progress to inform further strategies required to achieve hepatitis C virus elimination targets


With highest hepatitis C mortality rate in U.S., Oregon expands access to life-saving drugs

PBS News Hour
May 23, 2018

Watch the program

With highest hepatitis C mortality rate in U.S., Oregon expands access to life-saving drugs
New drugs can cure up to 95 percent of patients with hepatitis C, a virus that can be debilitating or deadly. And there’s been a 20 percent rise in new infections from 2015 to 2016 due to the opioid epidemic. In Oregon, a state hard-hit by the disease, new medicines combined with the big surge in those looking for treatment has led to a unique care model. Special correspondent Cat Wise reports.

Full Transcript

Judy Woodruff: Now the latest on a medical breakthrough that’s starting to have an impact on a hidden, deadly epidemic in this country. New drugs can cure up to 95 percent of patients with hepatitis C, a virus that often leads to debilitating or deadly results. The drugs can save lives, prevent expensive hospitalizations and liver transplants. But some states are feeling the squeeze of the cost of this medicine. Special correspondent Cat Wise has our report for our weekly series on the Leading Edge of science.

Cat Wise: Three-point-five million Americans are living with a potentially deadly virus, and half don’t even know it. It’s hepatitis C, a blood-borne pathogen which attacks the liver and can eventually cause serious liver problems, including cirrhosis and liver cancer. Three-quarters of those with the virus are baby boomers, exposed from unscreened blood transfusions, I.V. drug use, and other blood-to-blood contact prior to the early ’90s. But now the opioid epidemic has led to a 20 percent rise in new infections from 2015 to 2016. One state where the young and the old have been hit hard by the disease is Oregon. Oregon has the highest hepatitis C mortality rate, per capita, in the country. It’s estimated about 100,000 Oregonians have been infected with the virus and more than 500 die every year. It’s been a very difficult disease to treat, but over the last four years, there’s been a revolution in hep C drugs. Many are being cured around the country now, and here in Oregon, many are coming here to the Oregon Clinic for those treatments.

Dr. Kent Benner: We never talked about cure of hep C until the last few years, and now we’re all talking about cure of hep C.

Cat Wise: Dr. Kent Benner is a gastroenterologist and hepatologist at the clinic in Portland. He says people are still dying from the disease, often because they haven’t been tested and aren’t aware they have virus until they are quite sick. But Benner says much has changed since he first started treating patients several decades ago.

Dr. Kent Benner: Treatment at that time was interferon. This required injections, shots several times a week. Quite a few side effects. We felt we were doing well if we could cure 15 or 20 percent of patients. Since late 2013, there’s been a remarkable development from a number of different companies. They have developed drug combinations that provide 95 percent cure rates in patients we treat.

Cat Wise: Costly liver transplants are often the only option when the liver becomes too badly damaged. But at earlier disease stages, the liver often starts to heal once the medicines have cleared virus from the body.

Dr. Kent Benner: Not only are we seeing liver function improve, but patients with more advanced liver disease occasionally can come off the transplant list.

Cat Wise: Sixty-four-year-old Rob Shinney, who recently had knee surgery, is one of those cured by the new hep C drugs known as direct-acting antivirals, or DAAs. Like many others of his generation, he doesn’t really know how he contracted the virus. Under the care of Dr. Benner, Shinney began a three-month treatment in late 2016 after his liver showed signs of moderate scarring known as fibrosis. Tests later confirmed he was virus-free.

Rob Shinney: I had a serious chronic illness hanging over my head that I knew could kill me. And that’s gone now.

Cat Wise: We spoke at a local pub he visits now and again with his choir friends, something he never did when he had the virus.

Rob Shinney: I swear I felt like I was 20 years younger. I had energy. I could do things. It’s great just to be able to sit around and have a beer with everybody and, you know, just enjoy life. Cat Wise: The cost of the drugs used to cure Shinney, who has private insurance, aren’t cheap. Since Gilead Sciences’ Sovaldi first hit the market in late 2013 at a whopping $84,000 for a course of therapy, competitors have steadily lowered the costs. Last year, a new medication called Mavyret was released for around $26,000. Many payers often, though, negotiate even lower prices with the drug company. Still, the drugs are expensive, and they aren’t a vaccine. If someone is cured, they can become reinfected. Access to the drugs varies widely around the country. A report last year by two national advocacy organizations found that many public and private payers choose to limit access to DAAs due to their cost, as well as other concerns. Oregon is among a number of states which have had restrictive Medicaid requirements, including denying coverage to patients in the early stages of disease and those who are abusing drugs and alcohol. But some of those restrictions are beginning to ease.

Dr. Dana Hargunani: In January, we just started covering individuals with lower stages or lower levels of fibrosis.

Cat Wise: Dr. Dana Hargunani is the chief medical officer for the Oregon Health Authority, which oversees the state’s Medicaid program. She says, while the state is starting to expand access, costs are still a significant issue. Oregon has spent more than $94 million on the drugs since 2014, covering about 1,500 people.

Dr. Dana Hargunani: The newer treatments for hepatitis C have a significant budget impact for our state. We had to get additional funding through the legislative process. We’re trying to manage our limited resources to ensure coverage for those who need it immediately for the hepatitis C treatment, as well as all the other individuals in our Medicaid program.

Cat Wise: Hargunani says another reason the state delays coverage until patients have mild liver scarring, not everyone needs the medicines.

Dr. Dana Hargunani: One in five individuals who get infected with hepatitis C will spontaneously clear their infection. Right now, the data doesn’t help us understand how to know which individuals will need to have a high-cost drug to treat and cure their infection.

Dr. Brianna Sustersic: Luckily, he doesn’t have any evidence of cirrhosis.

Cat Wise: Dr. Brianna Sustersic is a medical director at Central City Concern, a federally funded health center in downtown Portland which serves a large number of homeless individuals, many of whom have substance abuse disorders; 25 percent to 50 percent of the patients have hep C.

Dr. Brianna Sustersic: The Medicaid requirements have limited access to treatment for many of our patients. From a public health standpoint, if we are able to treat the population who is contracting this, and spreading it, then we can move toward eradicating the disease.

Cat Wise: To prove that point, and to meet a big need, the clinic and a local syringe exchange program began a small drug company-sponsored study last year to treat patients who otherwise wouldn’t have qualified for the medications; 56-year-old Kim Trano is now virus-free thanks to that trial. She says she’s felt a lot of stigma being a recovering drug user and it was hard to learn she had initially been denied drug coverage. To those who would question giving expensive medicines to someone who might become reinfected, she says:

Kim Trano: Everyone is worthy of a chance. If I were to relapse, I would all precautions not to be reinfected. And that’s pretty easy to do. Most people know how to do that.

Cat Wise: The new medicines combined with the big surge in those looking for treatment has led to a unique care model. Chris Hulstein is not a doctor. He’s a clinical pharmacist and part of a new program at Portland’s Providence Hospital. Over the past year, about 50 patients have been successfully treated by Hulstein and his colleagues. Another 30 are currently in treatment.

Chris Hulstein: A lot of the specialists are very busy managing very complex patients, and that is their role. Having a pharmacist being able to manage the patient gets patients treated faster and more successfully than we ever have been able to do before.

Cat Wise: Hepatitis C advocates are now working with the state and private insurers to open up more access to the drugs. For the “PBS NewsHour,” I’m Cat Wise in Portland, Oregon.

Wednesday, May 23, 2018

HCV-Infected Patients With Diabetes Improve With Direct-Acting Antiviral Therapy: Presented at AACE

FirstWord Pharma

HCV-Infected Patients With Diabetes Improve With Direct-Acting Antiviral Therapy: Presented at AACE
By Michael Bassett
BOSTON -- May 22, 2018 -- Treatment of hepatitis C virus (HCV)-infected patients who have diabetes with direct-acting antiviral therapy results in significant and durable improvement in their diabetes, according to study presented here at the American Association of Clinical Endocrinologists 27th Annual Scientific & Clinical Congress (AACE)...

Although 66% of the patients had no improvement in diabetes with HCV eradication, 10% of the patients showed improvement but not sustained, and 24% experienced sustained improvement...

Drugmakers Blamed For Blocking Generics Have Jacked Up Prices And Cost U.S. Billions

Drugmakers Blamed For Blocking Generics Have Jacked Up Prices And Cost U.S. Billions
May 23, 2018
Sydney Lupkin, Kaiser Health News

Makers of brand-name drugs called out by the Trump administration for potentially stalling generic competition have hiked their prices by double-digit percentages since 2012 and cost Medicare and Medicaid nearly $12 billion in 2016, a Kaiser Health News analysis has found.

As part of President Donald Trump’s promise to curb high drug prices, the Food and Drug Administration posted a list of pharmaceutical companies that makers of generics allege refused to let them buy the drug samples needed to develop their products. For approval, the FDA requires so-called bioequivalence testing using samples to demonstrate that generics are the same as their branded counterparts.

The analysis shows that drug companies that may have engaged in what FDA Commissioner Scott Gottlieb called “shenanigans” to delay the entrance of cheaper competitors onto the market have indeed raised prices and cost taxpayers more money over time.

The FDA listed more than 50 drugs whose manufacturers have withheld or refused to sell samples, and cited 164 inquiries for help obtaining them. Thirteen of these pleas from makers of generics pertained to Celgene’s blockbuster cancer drug Revlimid, which accounted for 63 percent of Celgene’s revenue in the first quarter of 2018, according to a company press release.

The brand-name drug companies “wouldn’t put so much effort into fighting off competition if these weren’t [such] lucrative sources of revenue,” said Harvard Medical School instructor Ameet Sarpatwari. “In the case of a blockbuster drug, that can be hundreds of millions of dollars of revenue for the brand-name drugs and almost the same cost to the health care system.”

Indeed, a KHN analysis found that 47 of the drugs cost Medicare and Medicaid almost $12 billion in 2016. The spending totals don’t include rebates, which drugmakers return to the government after paying for the drugs upfront but are not public. The rebates ranged from 9.5 percent to 26.3 percent for Medicare Part D in 2014, the most recent year that data are available.

The remaining drugs do not appear in the Medicare and Medicaid data.

By delaying development of generics, drugmakers can maintain their monopolies and keep prices high. Most of the drugs cost Medicare Part D more in 2016 than they did in 2012, for an average spending increase of about 60 percent more per unit. This excludes drugs that don’t appear in the 2012 Medicare Part D data.

Revlimid cost Medicare Part D $2.7 billion in 2016, trailing only Harvoni, which treats hepatitis C and is not on the FDA’s new list. The cost of Revlimid, which faces no competition from generics, has jumped 40 percent per unit in just four years, the Medicare data show, and cost $75,200 per beneficiary in 2016.

Some drugs on the FDA’s list, including Celgene’s, are part of a safety program that can require restricted distribution of brand-name drugs that have serious risks or addictive qualities. Drugmakers with products in the safety program sometimes say they can’t provide samples unless the generics manufacturer jumps through a series of hoops “that generic companies find hard or impossible to comply with,” Gottlieb said in a statement.

The Department of Health and Human Services Office of Inspector General issued a report in 2013 that said the FDA couldn’t prove that the program actually improved safety, and Sarpatwari said there’s evidence drugmakers are abusing it to stave off competition from generics.

Gottlieb said the FDA will be notifying the Federal Trade Commission about pleas for help from would-be generics manufacturers about obtaining samples, and he encouraged the manufacturers to do the same if they suspect they’re being thwarted by anticompetitive practices.

Celgene spokesman Greg Geissman said the company has sold samples to generics manufacturers and will continue to do so. He stressed maintaining a balance of innovation, generic competition and safety.

“Even a single dose of thalidomide, the active ingredient in Thalomid, can cause irreversible, debilitating birth defects if not properly handled and dispensed. Revlimid and Pomalyst are believed to have similar risks,” Geissman said.

The highest number of pleas for help related to Actelion Pharmaceuticals’ pulmonary hypertension drug Tracleer. In 2016, that drug cost Medicare $90,700 per patient and more than $304 million overall. Meanwhile, spending per unit jumped 52 percent from 2012 through 2016.

Actelion was acquired by Johnson & Johnson’s pharmaceutical arm, Janssen, in 2017.

Actelion spokeswoman Colleen Wilson said that the company “cooperate[s]” with makers of generic drugs and “has responded to all requests it has received directly from generic manufacturers seeking access to its medications for bioequivalence testing.”

PhRMA, the trade group for makers of brand-name pharmaceuticals, said the FDA’s list was somewhat unfair because it lacked context and responses from those it represents.

“While we must continue to foster a competitive marketplace, PhRMA is concerned that FDA’s release of the ‘inquiries’ it has received lacks proper context and conflates a number of divergent scenarios,” said PhRMA spokesman Andrew Powaleny.

Congress is considering the CREATES Act, which stands for “Creating and Restoring Equal Access to Equivalent Samples” and would foster competition in part by allowing generics manufacturers to sue brand-name drug manufacturers to compel them to provide samples.

The bill’s sponsor, Sen. Patrick Leahy (D-Vt.), said more transparency from the FDA is helpful, but more work from the agency is needed to end the anticompetitive tactic. “With billions of dollars at stake, a database alone will not stop this behavior,” Leahy said.

Co-sponsor Sen. Chuck Grassley (R-Iowa), chairman of the Judiciary Committee, expressed similar sentiments, telling KHN: “The CREATES Act is necessary because it would serve as a strong deterrent to pharmaceutical companies that engage in anticompetitive practices to keep low-cost generic drugs off the market.”

The FDA hasn’t come out in support of CREATES. “They should know that this is going to require a legislative solution,” Sarpatwari said. “Why are they not stepping into this arena and saying that?”

This article was reprinted from with permission from the Henry J. Kaiser Family Foundation. Kaiser Health News, an editorially independent news service, is a program of the Kaiser Family Foundation, a nonpartisan health care policy research organization unaffiliated with Kaiser Permanente.

Tuesday, May 22, 2018

More patients with severe alcoholic hepatitis receiving liver transplants

More patients with severe alcoholic hepatitis receiving liver transplants
Medical centers willing to perform transplants without mandated six-month wait

Washington, DC (May 22, 2018) -- Increasingly, liver transplant centers are changing a long-standing practice of delaying potentially life-saving liver transplantation for patients with severe alcoholic hepatitis until after they stopped drinking alcohol for six months, according to a new study scheduled for presentation at Digestive Disease Week® (DDW) 2018.

Study implications
"Liver transplant for severe alcoholic hepatitis is being increasingly accepted, with positive outcomes, and the hope is that more and more patients will be evaluated for transplants," said Saroja Bangaru, MD, chief resident in internal medicine at the University of Texas Southwestern Medical Center, Dallas, and co-author of the study. "The hope is that survival rates are encouraging enough for centers, so that even more of them will reverse past practices."

Severe alcoholic hepatitis has an extremely high mortality rate. The primary treatment option has been the use of steroids, predominantly prednisolone. But, many patients do not respond to steroids, and a significant percentage of them will die within three months.

Historically, centers would not perform transplants until patients had stopped drinking for six months due to concerns about a return to drinking after transplant. Additionally, there was a perceived high risk that patient's continued drinking would cause them to miss medical appointments and failure to take their immunosuppressant medications, which prevent organ rejection, all of which could contribute to transplant failure.

Only in recent years have limited studies begun to show greater success for transplants for severe alcoholic hepatitis, Bangaru said. These studies have also shown that a variety of other factors -- aside from recent drinking -- influence whether a patient relapses. These include whether the patient has good social support, suffers from psychiatric ailments and accepts that they have an alcohol problem. "These studies suggest that predicting risk of relapse is much more complicated than just duration of abstinence," Bangaru said.

Study design and results
Researchers gathered data from 45 transplant centers, of which 23 said they were now performing such transplants. Among those, 17 centers reported that patients had a one-year survival rate of more than 90 percent, which is higher than that reported in several previous studies.

The survey found that centers have become more willing to perform transplants, as long as patients are carefully screened. Researchers reported that centers use highly selective criteria in approving candidates for transplant, assessing their medical history, social support system and whether they have additional health problems, particularly psychiatric disorders.

"If patients are selected well, according to these criteria, it allows for the excellent survival that we are seeing post-transplant," Bangaru said. Past policy has done a disservice to those patients who were previously unaware that they had liver disease. "Some patients come in for the first time with severe alcoholic hepatitis, and no one has ever told them to stop drinking. Because they are not eligible for transplant, they have a really high mortality rate."

The survey also concluded that most transplant centers had "inadequate" post-transplant support for patients. While most offered the services of social workers, only a limited number provided psychiatric or group therapy support that could be very important in helping patients avoid relapse and further medical problems.

Next steps
Dr. Bangaru said further study is needed to encourage more transplants, in particular a controlled clinical trial that follows survival rates over one, three and five years, along with an assessment of rates of alcoholic relapse.

DDW presentation details
Dr. Saroja Bangaru will present data from the study, "Increased use of liver transplantation as therapeutic option for severe alcoholic hepatitis," abstract Sa1457, on Saturday, June 2, at noon EDT. For more information about featured studies, as well as a schedule of availability for featured researchers, please visit

Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place June 2-5 at the Walter E. Washington Convention Center in Washington, DC. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. 
More information can be found at

FDA warns companies selling illegal, unapproved kratom products marketed for opioid cessation, pain treatment and other medical uses

The U.S. Food and Drug Administration has issued warning letters to three marketers and distributors of kratom products – Front Range Kratom of Aurora, Colorado; Kratom Spot of Irvine, California and Revibe, Inc., of Kansas City, Missouri – for illegally selling unapproved kratom-containing drug products with unproven claims about their ability to help in the treatment of opioid addiction and withdrawal. The companies also make claims about treating pain, as well as other medical conditions like lowering blood pressure, treating cancer and reducing neuron damage caused by strokes.
“Despite our warnings that no kratom product is safe, we continue to find companies selling kratom and doing so with deceptive medical claims for which there’s no reliable scientific proof to support their use,” said FDA Commissioner Scott Gottlieb, M.D. “As we work to combat the opioid epidemic, we cannot allow unscrupulous vendors to take advantage of consumers by selling products with unsubstantiated claims that they can treat opioid addiction. Far from treating addiction, we’ve determined that kratom is an opioid analogue that may actually contribute to the opioid epidemic and puts patients at risk of serious side effects. If people believe that the active ingredients in kratom have drug-like effects that can treat pain or addiction, then the FDA is open to reviewing that data under our new drug approval process. In the meantime, I promised earlier this year that the FDA would step up our actions against unapproved and unsafe products that are being deceptively marketed for the treatment of opioid addiction and withdrawal symptoms. At the same time, we also promised to make the approval process more efficient for novel, safe and effective medical treatments aimed at the treatment of addiction; and to help more people suffering from addiction get access to approved therapies. In fulfilling these commitments, we’ll continue to take enforcement actions against unscrupulous products to protect the public health.”
The FDA continues to warn consumers not to use Mitragyna speciosa, commonly known as kratom, a plant which grows naturally in Thailand, Malaysia, Indonesia and Papua New Guinea. The FDA is concerned that kratom, which affects the same opioid brain receptors as morphine, appears to have properties that expose users to the risks of addiction, abuse and dependence. There are no FDA-approved uses for kratom, and the agency has received concerning reports about the safety of kratom.
The FDA is actively evaluating all available scientific information on this issue and continues to warn consumers not to use any products labeled as containing the botanical substance kratom or its psychoactive compounds, mitragynine and 7-hydroxymitragynine. The FDA encourages more research to better understand kratom’s safety profile, including the use of kratom combined with other drugs.
The companies receiving warning letters use websites where they take orders for kratom products or they use social media to make unproven claims about the ability of their kratom drug products to cure, treat, or prevent a disease, which is against the law. Examples of claims being made by these companies include:
  • “Along with helping drug addiction, the health benefits of kratom leaves include their ability to lower blood pressure, relieve pain, boost metabolism, increase sexual energy, improve the immune system, prevent diabetes, ease anxiety, eliminate stress, and induce healthy sleep.”
  • “The mood elevation qualities of kratom reduces opiate withdrawal effects.”
  • “Kratom, like any other pain killer, relieves temporary or even chronic pain.”
  • “This plant can relieve headaches, vascular pain, arthritic pain, muscle pain among others.”
  • “Kratom can be used as a remedy for stroke-related ailments and condition as it is a powerful antioxidant that works to reduce neuron damage.”
  • “It can . . . help in lowering blood pressure.”
  • “Kratom is also said to have elements that control blood sugar level in the body for diabetic patients.”
  • “It is said, that kratom is very effective against cancer.”
Health fraud scams like these can pose serious health risks. These products have not been demonstrated to be safe or effective and may keep some patients from seeking appropriate, FDA-approved therapies. Selling these unapproved products with claims that they can treat opioid addiction and withdrawal and treat other serious medical conditions is a violation of the Federal Food, Drug, and Cosmetic Act.
Reducing the number of Americans who are addicted to opioids and cutting the rate of new addiction is one of the FDA’s highest priorities. This work includes promoting more widespread innovation and access to opioid addiction treatments for the more than 2 million of Americans with an opioid use disorder. The FDA is taking new steps to make safe and effective medication assisted treatments (MAT) available to those who suffer from opioid use disorder and to reduce the stigma that is sometimes associated with use of these therapies. Using products with unsubstantiated claims may prevent those addicted to opioids from seeking treatments that have been demonstrated to be safe and effective. Reliance on products with unsubstantiated claims may delay their path to recovery and put them at greater risk of addiction, overdose and death. In fact, patients receiving FDA-approved medication-assisted treatment cut their risk of death in half, according to the Substance Abuse and Mental Health Services Administration.
The warning letters included more than 65 kratom products. Some of these products include:
Front Range Kratom:
  • “Maeng Da Red Vein Powder”
  • “Maeng Da White Vein Capsules”
  • “Liquid Kratom Red Maeng Da Enhanced Pain Formulation”
  • “Bali White Vein Kratom Powder”
  • “Bali Green Vein Powder”
  • “Maeng Da White Energizing Formula”
Kratom Spot:
  • “Red Thai Kratom Powder”
  • “Indo White Vein Kratom Powder”
  • “Borneo White Vein Kratom Powder”
  • “Green Malay Kratom Powder”
  • “Super Green Indo Kratom Capsules”
  • “Ultra Enhanced Malay Kratom Powder”
  • “Kratom Extract 8x Kratom Powder”
  • “50x Black Diamond Extract”
  • “Green Horn Kratom”
  • “Green Indo”
  • “Green Sumatra,” “Lucky 7”
  • “Red Borneo”
  • “Super Elephant”
  • “White Sumatra”
  • “Yellow Vietnam Kratom”
The FDA requested responses from each of the companies within 15 working days. The companies are directed to inform the agency of the specific actions taken to address each of the agency’s concerns. The warning letters also state that failure to correct violations may result in law enforcement action such as seizure or injunction.
Previous FDA testing also confirmed salmonella contamination in kratom products distributed by Revibe. On March 26, 2018, the FDA contacted Revibe regarding a recall of all Revibe kratom containing products that may be contaminated with salmonella. On April 3, 2018, the agency oversaw the destruction of products at Revibe’s facility, but, as of April 19, 2018, the company has not provided the FDA information to confirm that they have recalled the products it distributed. The FDA reminds consumers of the risks and urges them not to use these or any other kratom products.
Health care professionals and consumers are encouraged to report any adverse events related to these products to the FDA’s MedWatch Adverse Event Reporting program. To file a report, use the MedWatch Online Voluntary Reporting Form. The completed form can be submitted online or via fax to 800-FDA-0178.
The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.