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Alan Franciscus
HCV Advocate
HBV Advocate

Drugs in Development / Clinical Trials—Updated October 13, 2014

Thursday, November 20, 2014

France pegs Gilead hepatitis C drug at "lowest price in Europe"

Nov 20 (Reuters) - France has negotiated a big discount for Gilead Sciences Inc's controversial new hepatitis C drug Sovaldi, under a government deal that ensures it will be fully reimbursable by health-funding schemes.

The Economic Committee for Health Products (CEPS) has fixed the price of a box of Sovaldi at 13,667 euros before tax, a reduction of 5,000 euros on the original price and "the lowest price in Europe", the Health Ministry said on Thursday.

Twelve weeks of treatment will now cost 41,000 euros ($51,373) before tax, against 56,000 euros previously.


At the Crossroads, Part 4: New Hep C Drugs Promise A Cure, For A Big Price

This year marks the 25th anniversary of the discovery of the hepatitis C virus. Since then, people with hepatitis C have had limited – and not very effective – options for treatment.

Until now.

Revolutionary new treatments have hit the market in just the last few months. But they’re so expensive health insurers are balking at the price.

Part four of our series “At the Crossroads: The Rise of Hepatitis C and the Fight to Stop it” looks at the high cost of these new treatments and who’s paying for them.

Listen to the podcast and read the transcript here....

Intervention to Improve HCV Treatment Uptake and Adherence in HIV/HCV Coinfection

End-stage liver disease, predominantly due to hepatitis C virus (HCV) infection, is one of the leading causes of death in person living with HIV infection. While HCV is curable and recent advances in treatment have increased the rates of cure, few patients with HIV and HCV are being treated to cure HCV. Based on formative research, the investigators developed the "Psychosocial Readiness Evaluation and Preparation for hepatitis C treatment (PREP-C)". PREP-C is a clinical interview that healthcare providers of diverse disciplines can be trained to administer. It provides an assessment of a client's psychosocial readiness to begin HCV treatment and identifies domains of functioning which require intervention to improve treatment readiness. PREP-C (www.prepC.org) is also a telemedicine resource for health care providers. Under this protocol, the existing PREP-C clinical interview (or assessment) is incorporated with a behavioral intervention. This study tests the integrated assessment-behavioral intervention to increase HCV treatment initiation among HIV-co-infected patients. The assessment-behavioral intervention under this protocol is conducted in two phases, an Intervention Development phase and a Pilot Randomized Clinical Trial (RCT) phase.

Findings from this vanguard study will inform the design parameters of a larger, more rigorous evaluation in an R01 application, if results are promising. The PREP-C web-based assessment and intervention package is designed to be scalable and can be disseminated through the live PrepC.org web site. The proposed study is innovative in that it seeks to develop the first web-based intervention for health care providers to use to increase HCV treatment initiation in HIV/HCV-co-infected persons. The study can have a major public health impact by providing needed structured resources for health care providers to increase rates of HCV treatment initiation in HIV/HCV-co-infected persons, thereby reducing mortality due to end-stage liver disease.


Hepatitis C Around the World: Hepatitis C in Canada

Hepatitis C Around the World: Hepatitis C in Canada
—Cheryl Reitz, MA, & CD Mazoff, PhD    

Some people argue that the general ignorance about hepatitis C (HCV) in Canada is a legacy of the Canadian government’s attempt to bury the memory of the tainted blood scandal of the 1980’s when thousands of Canadians were infected with HIV and HCV via tainted blood products purchased from the U.S and not tested for HCV to save money, although a test was available.1  The legacy of this tragedy is still with us in Canada, as those infected (aware and unaware) age, and their disease progresses to the point of serious illness.

Accurate statistics are almost impossible to find because they are either really out of date or not representative of real numbers, since they are based on different model projections from different agencies that are not sharing data.

Most people still cite the Public Health Agency of Canada (PHAC)2 statistics published in 2012 which are derived from surveys conducted between 2005-2010.  These numbers are tremendously out of date. 

According to the 2010 statistics, almost 0.8% of Canada’s population has hepatitis C.  Adjusted for 2014 these figures are approx. 280,000 for a population of 35 million.

Other numbers that have been derived from the collected surveys are:
  • 69% of injection drug users in Canada have hepatitis C (2005-2008).
  • 28% of Canada’s 15,000 prison inmates have hepatitis C [adjusted for 2014].
  • 5% of gay and MSM have hepatitis C (2005-2008).
  • 5% of street-involved youth have hepatitis C (2005-2006).
  • 3% of 850,000 First Nations people have hepatitis C [adjusted for 2014].
  • 3% of Canada’s immigrant population is HCV positive [adjusted for 2014].3
However more recent studies suggest that the Canadian numbers are underestimated: Since the epidemiology of hepatitis C in Canada is similar to the U.S., prevalence may be similar, i.e., about 350,000 to 400,000 cases — again much higher than previously thought.4 

Further, a new documentary on hepatitis C in Canada called “Deal With It: Untold Stories of Hepatitis C in Canada,” points out that when a recent sampling was done by Statistics Canada to determine awareness of infection, 70% of those who tested positive did not know they were infected.5

Regional differences in the epidemiology of hepatitis C in Canada, are shown in Figure 8.4

Canada has no “National Strategy” for dealing with hepatitis C, and the Federal and Provincial governments often (as in the United States) have different agendas and do not work together well.

There is no Federal screening and treatment plan in place, although we are hoping that one-time-only, “non-mandatory” Baby Boomer Cohort testing will be put in place soon.  Advocates such as those at HepCBC have been calling for national testing since 2000 when they put the world’s first HCV “Get Tested” bus ads up in Victoria, BC.  Testing is very important considering the growing burden of the disease in Canada, where, since the 1970s “the incidence rate of liver cancer has tripled in Canadian men and doubled in Canadian women, rising every year by 3.6% in men and 1.7% in women.”6

While drug approval happens at the Federal level, the decision to treat is left at the provincial level where the cost of treatment and access to it are decided.  All provinces and territories have their own versions of “Pharmacare” (free or low-cost medications for low- and middle-income), and there are private group insurance plans as well. The province of Québec provides Pharmacare coverage for treatment-naïve patients with genotypes 1 and 4 HCV infection regardless of disease severity, just a qualifying recommendation from the referring physician.  However, in Ontario and BC simeprevir plus PEG/RBV is covered for genotype 1 only (naïve, relapser, non-responder), and liver fibrosis F2 or higher.  No interferon-free regimes or off-label access is covered by any provincial Pharmacare plans as yet. However, approved drugs can be obtained at full price or via some expensive private health plans.

Registered First Nations and Inuit people get coverage for HCV drugs through the Non-Insured Health Benefits Program, which, like Quebec, has a very different approval process than the rest of Canada.  Also note that all the provinces and territories except Quebec negotiate as a group with the drug companies to obtain the best bulk pricing: “Most of Canada’s provinces and territories have joined together to form the Pan-Canadian Pharmaceutical Alliance (PCPA), with the goal of negotiating better prices on both brand name and generic prescription drugs.”  While patient groups have the opportunity to provide input to the Common Drug Review, they do not currently have a “seat at the table” for PCPA negotiations. 7

At the time of this writing, simeprevir + interferon (Galexos), Sovaldi + ribavirin, and Harvoni have been approved by the federal government (Public Health Canada) for use in Canada; but the access to and coverage of these drugs is still controlled by the provinces and the current situation is so fluid it is not easy to keep track of rapidly-changing coverage and prices of the new DAAs in Canada’s provinces and territories.

The price of drugs is almost always lower in Canada than in the USA, and this seems to follow for HCV drugs as well.  For example, Sovaldi in Canada will likely cost $640 per pill, or $55,000 to $110,000 per patient for treatment, according to a spokesperson from the BC Ministry of Health.8

Particular challenges for those trying to eliminate HCV in Canada include our great size (much larger than the US) and relatively small population (35 million), most of which is concentrated near the US border, leaving huge swaths of sparsely-populated rural areas (mostly in the Prairie Provinces and in the northern 2/3 of our country) in which HCV treatment infrastructure is limited or non-existent.

As the situation now stands, more people are contracting hepatitis C every year in Canada than are being treated for it.  The new DAAs – especially the interferon-free formats, with their shorter treatment times and positive side-effect profiles – will have a profound effect on this trend by giving medical caregivers more time, enabling them to treat more patients. However, in order to actually eliminate the virus from Canada will require more than this: At least a four-to-five-fold increase in the treatment rate per year. The tools now exist to bring about such an increase, but it would require a degree of commitment from Canada’s government that patients have yet to see here.

In 2010, local and provincial-level hepatitis B and C patient groups and organizations in Canada joined forces to form an umbrella organization, Action Hepatitis Canada (AHC – at www.actionhepatitiscanada.ca). Thanks to AHC, hepatitis C patients are speaking with one voice, and much more loudly these days, lobbying the drug companies to lower their prices while lobbying the government to fast-track drug approvals and to direct more of its resources to fighting HCV. But they aren’t only interested in eliminating HCV in Canada, they are also involved in the fight to eradicate HCV entirely from the rest of the world.

1. Factor 8: The Arkansas Prison Blood Scandal, a film by Kelly Duda, Review by C.D. Mazoff:  HCV Advocate, March 2007, p.7.  http://hcvadvocate.org/news/newsLetter
/2007 /advocate0307.html#4

2. Hepatitis C in Canada:2005-2010 Surveillance Report. Public HealthAgency of Canada; 2011.
3.The epidemiology of hepatitis C in Canada (CATIE 2013) http://www.catie.ca/en/fact-sheets/epidemiology

4. Liver Disease in Canada: A Crisis in the Making: An Assessment of Liver Disease in Canada Published by the Canadian Liver Foundation in March, 2013. http://www.liver.ca/files/PDF/Liver_Disease_Report
_2013 /Liver_Disease_in_Canada_-_E.pdf

5. Deal With It: Untold Stories of Hepatitis C in Canada. Bang Albino Films, 2014
6.Liver Cancer on the Rise: Canadian Cancer Society 2013 http://www.cancer.ca/en/about-us/for-media/media-releases /national/2013/liver-cancer-on-the-rise-cancer-statistics/?region=bc
7. http://healthydebate.ca/2014/10/topic/cost-of-care

8. http://thetyee.ca/News/2014/07/28/Hep-C-Miracle-Treatment-BC/

Cheryl Reitz is on the Board of Directors of HepCBC and HepCBC’s representative on the Executive of Action Hepatitis Canada; C.D. Mazoff, the Managing Editor & Webmaster of the HCV Advocate, is a former Executive Director of HepCBC where he currently sits on the Board.


Tuesday, November 18, 2014

UK: NHS asks Nice to delay ground-breaking hepatitis C drug

It is a drug that cures hepatitis C in 90 per cent of cases and was considered ground-breaking when it came on to the market.

Manufactured by Gilead, Sofosbuvir was licenced for use late last year. And in April this year, NHS England took the unusual step of setting up a special access scheme so patients with less than a year to live were able to be treated without waiting for the National Insitute for Health and Care Excellence (Nice) to evaluate whether it should become routinely available on the NHS.

But it is expensive – £35,000 for a 12 week course. So now NHS England is balking at the potential cost. In fact so much so, this programme has learned that they have asked Nice to delay implementation.

- See more at: http://blogs.channel4.com/victoria-macdonald-on-health-and-social-care/nhs-asks-nice-delay-groundbreaking-hepatitis-drug/2625#sthash.Kiw2q4xS.dpuf

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

-- Once-Daily Single Tablet Regimen Eliminates the Need for Interferon and Ribavirin for Patients with Genotype 1 and 4 Hepatitis C without Cirrhosis or with Compensated Cirrhosis --

FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 18, 2014-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the European Commission has granted marketing authorization for Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg), the first once-daily single tablet regimen to treat the majority of chronic hepatitis C genotype 1 and 4 infection in adults. Harvoni combines the NS5A inhibitor ledipasvir (LDV) with the nucleotide analog polymerase inhibitor sofosbuvir (SOF), approved by the European Commission under the tradename Sovaldi® in January 2014.

Harvoni is indicated for the treatment of chronic hepatitis C virus (HCV) in adults and is recommended in treatment-naïve and treatment-experienced cirrhotic and non-cirrhotic genotype 1 and 4 patients with a treatment duration of 12 or 24 weeks depending on prior treatment history and cirrhosis status. Eight weeks of treatment with Harvoni may be considered in non-cirrhotic treatment-naïve genotype 1 patients. In genotype 1 and 4 patients with decompensated cirrhosis, and genotype 3 patients with cirrhosis and/or prior treatment failure, Harvoni should be used in combination with ribavirin for 24 weeks. Harvoni is also indicated for patients with HCV who have HIV co-infection.

Today’s marketing authorization is based on the clinical development program that included more than 2,000 patients with HCV infection, and follows an accelerated assessment by the European Medicines Agency, a designation that is granted to new medicines of major public health interest. It allows for the marketing of Harvoni in all 28 countries of the European Union (EU).

“Genotype 1 patients living with hepatitis C in Europe and the physicians who treat them have been waiting for a treatment advance like this for decades,” said Graham Foster, MD, Professor of Hepatology, Queen Mary University of London. “With Harvoni, we have the potential to transform the way we treat people living with the most prevalent form of hepatitis C in Europe. We can now expect very high SVR rates, and for many patients, we can eliminate the need for interferon injections and ribavirin and offer a cure in a once-daily tablet.”

The marketing authorization is supported primarily by data from three Phase 3 studies, ION-1, ION-2 and ION-3. These studies evaluated eight, 12 or 24 weeks of treatment with Harvoni, with or without ribavirin, among nearly 2,000 genotype 1 HCV patients with compensated liver disease.

These studies included non-cirrhotic treatment-naïve patients (ION-3), cirrhotic and non-cirrhotic treatment-naïve patients (ION-1) and cirrhotic and non-cirrhotic patients who failed prior therapy with an interferon-based regimen, including regimens containing an HCV protease inhibitor (ION-2).

The primary endpoint for each study was sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV. In these studies, ribavirin was not shown to increase response rates. Trial participants in the ribavirin-free arms (n=1,080) achieved SVR12 rates of 94 to 99 percent.

The approval was also supported by preliminary data from the SOLAR-1 trial, which evaluated difficult to treat patients with decompensated cirrhosis and patients who have undergone liver transplantation, and from the ERADICATE trial, which evaluated genotype 1 HCV patients co-infected with HIV. The primary endpoint in these studies was SVR12. At the time of submission, only preliminary results were available. In the SOLAR-1 trial, participants with decompensated cirrhosis receiving a 12-week treatment regimen of Harvoni plus ribavirin had an SVR4 rate of 90 percent (n=45/50). In post-liver transplant patients without decompensated liver disease, SVR4 rates were greater than 95 percent (n=109). In an interim analysis of the ERADICATE trial, 40 of the 50 patients had reached 12 weeks post treatment and had SVR12 rates of 98 percent (n=39/40).

The ELECTRON-2 trial, a Phase 2 open-label study, provided preliminary data on genotype 3 infected HCV patients demonstrating 100 percent (n=26/26) SVR12 when Harvoni was used in combination with ribavirin for 12 weeks.

In these clinical studies, fatigue and headache were more common in patients treated with Harvoni compared to placebo.

Harvoni was approved by the U.S. Food and Drug Administration and Health Canada in October 2014 and in New Zealand in November 2014. Regulatory submissions for Harvoni are pending in Japan and Switzerland. Sovaldi as a single agent is approved for use in the European Union and in the United States, Canada, Australia, New Zealand, Egypt, Switzerland and Turkey.

Important Safety Information
The summary of product characteristics of co-prescribed medicinal products should be consulted before starting therapy with Harvoni.
  • Harvoni should not be administered concomitantly with other medicinal products containing sofosbuvir.
  • In clinical studies, fatigue and headache were more common in patients treated with Harvoni compared to placebo.
  • Contraindications include hypersensitivity to the active substances or to any of the excipients. Co-administration with rosuvastatin or St. John’s wort (Hypericum perforatum) is contraindicated. Co-administration with certain P-glycoprotein (P-gp) inducers (e.g. rifampicin, carbamazepine and phenytoin) is not recommended. Monitoring of digoxin and dabigatran is recommended when used with Harvoni. Caution and frequent renal monitoring is recommended for co-administration with certain HIV antiretroviral regimens. 
  • Safety has not been established in patients with severe renal impairment. For patients on statins dose reduction should be considered and careful monitoring for statin adverse events (myopathy and rhabdomyolysis) should be undertaken. A Summary of Product Characteristics is available at www.ema.europa.eu.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

- See more at: http://gilead.com/news/press-releases/2014/11/european-commission-grants-marketing-authorization-for-gileads-harvoni-ledipasvirsofosbuvir-the-first-single-tablet-regimen-to-treat-the-majority-of-chronic-hepatitis-c-patients-with-genotype-1-and-4#sthash.YcamaUon.dpuf

Hepatitis C Antiviral Resistance Revealed

Scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) say recent research has shed light on the response of the hepatitis C virus (HCV) to targeted therapeutics and provided new insights about HCV’s role in cancer development. Their work (“Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors”), published in Nature Communications, focused on microRNA genes, a type of regulatory gene, and used whole-genome sequencing of the virus to challenge conventional wisdom about how the virus responds to emerging therapies.

Their findings, note the researchers, may contribute to more effective development of hepatitis C drugs in the future and to more personalized treatment for patients.

In this new study, Mount Sinai researchers examined HCV response to an experimental treatment that targets and blocks the supply of a microRNA (miR-122) that the virus needs for infection of human cells. Contrary to expectations, they found that depleting the supply of miR-122 could trigger drug resistance with the emergence of HCV strains able to infect cells with negligible levels of the microRNA. This information could be used for more effective dosing of drugs targeting this gene, as well as for pre-treatment analysis to determine which patients may respond best to this class of drugs.