March 18, 2014

Provided by hep Coalition

“We are witnessing a revolution in the treatment of hepatitis C virus with powerful molecules capable of curing the infection. There is no question that these treatments that can save millions of lives must be made universally available at an affordable price.”

Pr. Françoise Barré-Sinoussi, 2008 Nobel Laureate in Medicine

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Background: the HCV pandemic
185 million people across the world are infected with HCV; 150 million are chronically infected. The HCV pandemic is concentrated in middle-income countries (MICs); while 15% of the 150 million people with chronic HCV live in high-income countries (HICs), 72% live in MICs and 13% in low-income countries (LICs). It is estimated that HCV-related liver complications kill 350,000 people annually. Currently, the standard of care is injectable peg-interferon (PEG-IFN) used in combination with ribavirin (RBV). The cure rate is 50-75%, and the treatment is associated with strong side effects. Worldwide, only a tiny percentage of people with HCV have access to treatment.

2014, a turning-point in the history of the pandemic
New treatments recently approved or soon to be authorized will offer a range of advantages compared with their predecessors: multigenotypic activity, fewer side effects, and higher cure rates, including for those in advanced stages of infection.

These direct-acting antiretrovirals (DAAs), are bringing with them great hope for millions of people, as their use may lead to excellent cure rates. Gilead’s new nucleotide polymerase inhibitor/DAA sofosbuvir (SOF) was approved by the EMA in November 2013 and by United States FDA in December 2013. The cure rate with SOF is close to 90% according to recent clinical trials results. Janssen’s simeprevir also received FDA approval in November 2013. Bristol-Myers Squibb (BMS) has submitted daclatasvir to the FDA. SOF will be most likely be followed by other DAAs marketed by AbbVie, Janssen, and BMS before the end of 2014.

The issue of access
Although these new molecules will improve the quality of life of people with HCV and increase the number of people cured, their price will be out of reach of most of the people who need it. Gilead, like the other firms, is planning to apply different marketing strategies: “standard prices” in HICs, “tiered pricing” in MICs, and voluntary licencing in LICs. This analysis, using epidemiological data specific to HCV, tries to determine whether the strategies employed by pharmaceutical companies would be good for access.

While experts estimate that the production cost of SOF is USD68-136 (per person for 12 weeks), in HIC, SOF is sold USD1,000 per pill or USD80,000-90,000 per person for 12 weeks in the United States - where it is estimated that 5,367,834 persons live with HCV. As a comparison, the median household income in the country is USD51,017 per year, and while it is estimated that 48 million of Americans do not have any health insurance. In France, the cost of SOF is set at USD905 per pill (USD76,000 per person for 12 weeks). According to calculations made on InVs/ANRS epidemiological data, to provide SOF to 55 percent of the 232,196 people affected by chronic HCV in France and who need treatment rapidly, it would be equivalent to the budget of the Assistance Publique des Hôpitaux de Paris for 2014 or 4 times what France has paid into the GFATM since 2001. In MICs, Gilead plans to sell SOF for at least USD2,000 (for a 12-week course). In Egypt, at a minimum price of USD2,000, the cost of SOF alone for 100% of people with HCV would represent fivetimes the country’s total 2011 public health expenditures. In Indonesia, it would little bit more than the total annual health budget in 2011. More generally, at the prices set by pharmaceutical companies, universal access would be practically unachievable, even in countries who have strongly committed to access to HCV care, such as Georgia, Thailand and Egypt.

During the first HCV World Community Advisory Board (CAB) that took place between February 22 and 25 2014 in Bangkok, Gilead gave more precisions on the scope of the SOF voluntary license and the countries covered. Excluding the most affected countries in terms of number of people with HCV, this license is failing to address the issue of access to SOF in LICs & MICs. Theoretically, this license leaves out 77,4 millions people with HCV from the access in LICs and MICs. But, does the license give any guarantee to provide to the 57,1 millions other covered by the scope of the license a real access to treatment? Given the fact that there is no Global Fund on HCV to purchase treatments, diagnostics, and monitoring for LICs & MICs, there are really little chance that countries such as DRC or Cameroon, who are covered in the scope of the license, will start treating people with sofosbuvir anytime soon. Given its very limited scope, the Gilead’s 60 countries voluntary license on SOF brings out the fact that its main objective is not to provide access to the people living in the countries included in the territory but to bind generic producers, mostly based in India, to prevent them to supply any excluded MICs (including China, Brazil, Thailand, Egypt, Indonesia, etc.). As for the other VLs signed in the case of HIV and projections made based on details of the HCV pandemic, they also fail to provide an appropriate answer to the HCV pandemic in LICs and MICs. Voluntary licensing will thus fail to respond to the HCV pandemic in the most affected countries and hinder the generic drug competition.

Learning the lessons from the fight against HIV/AIDS
If none of these strategies (standard pricing, tiered pricing, and voluntary licensing) are good in terms of access, what other possibilities exist? In the case of HIV/AIDS, the use of TRIPS flexibilities has shown great results for opening access and reducing drug prices. In India, the opposition and revocation of abusive patents have increased the competition and considerably helped to drive down drugs’ prices. In countries such as Thailand and Brazil, the use of compulsory licensing in the case of HIV/AIDS has led to a substantial drop of the price of medicines.

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Source

Journal of Hepatology

Article in Press

Ann-Brit Eg Hansen, Lars Haukali Omland, Henrik Krarup, Niels Obel, on behalf of the DANVIR cohort study

Received 22 December 2013; received in revised form 6 March 2014; accepted 7 March 2014. published online 18 March 2014.
Accepted Manuscript

Abstract

Background and aims

The association between Hepatitis C virus (HCV)-infection and fracture risk is not well characterized. We compared fracture risk between HCV-seropositive (HCV-exposed) patients and the general population and between patients with cleared and chronic HCV-infection.

Methods

Outcome measures were time to first fracture at any site, time to first low-energy and first non low-energy (other) fracture in 12,013 HCV-exposed patients from the DANVIR cohort compared with a general population control cohort (n = 60,065) matched by sex and age. Within DANVIR, 4500 patients with chronic HCV-infection and 2656 patients with cleared HCV-infection were studied.

Results

Compared with population controls, HCV-exposed patients had increased overall risk of fracture [adjusted incidence rate ratio (aIRR) 2.15, 95% Confidence Interval (CI) 2.03 – 2.28], increased risk of low-energy fracture (aIRR 2.13, 95% CI 1.93 – 2.35) and of other fracture (aIRR 2.18, 95% CI 2.02 – 2.34). Compared with cleared HCV-infection, chronic HCV-infection was not associated with increased risk of fracture at any site (aIRR 1.08, 95% CI 0.97 – 1.20), or other fracture (aIRR 1.04, 95% CI 0.91 – 1.19). The aIRR for low-energy fracture was 1.20 (95% CI 0.99 – 1.44).

Conclusions

HCV-exposed patients had increased risk of all fracture types. In contrast, overall risk of fracture did not differ between patients with chronic versus cleared HCV-infection, although chronic HCV-infection might be associated with a small excess risk of low-energy fractures. Our study suggests that fracture risk in HCV-infected patients is multi-factorial and mainly determined by lifestyle-related factors associated with HCV-exposure.

Abbreviations: HCV, hepatitis C virus, CI, confidence interval, aIRR, adjusted incidence rate ratio, BMD, bone mineral density, CRS, Civil Registration System, DNPR, Danish National Hospital Registry, I CD-8, International Classification of Diseases, revision 8, ICD-10, International Classification of Diseases, revision 8, IDU, intravenous drug use, CCI, Charlsons Comorbidity Index, IRR, incidence rate ratio, PY, person years of observation

Keywords: Fracture risk, Chronic HCV, Cleared HCV, Comorbidity

No full text is available. To read the body of this article, please view the PDF online.

Source

Journal of Hepatology

Article in Press

Sylvie Deuffic-Burban, Michaël Schwarzinger, Dorothée Obach, Vincent Mallet, Stanislas Pol, Georges-Philippe Pageaux, Valérie Canva, Pierre Deltenre, Françoise Roudot-Thoraval, Dominique Larrey, Daniel Dhumeaux, Philippe Mathurin, Yazdan Yazdanpanah

      Received 22 August 2013; received in revised form 4 February 2014; accepted 6 March 2014. published online 18 March 2014.
      Accepted Manuscript
      Abstract
      Background & Aims

    In treatment-naive patients mono-infected with genotype 1 chronic HCV, treatments with telaprevir/boceprevir (TVR/BOC)-based triple therapy are standard-of-care. However, more efficacious direct-acting antivirals (IFN-based new DAAs) are available and interferon-free (IFN-free) regimens are imminent (2015).

    Methods

    A mathematical model estimated quality-adjusted life years, cost and incremental cost-effectiveness ratios of (i) IFN-based new DAAs vs. TVR/BOC-based triple therapy; and (ii) IFN-based new DAAs initiation strategies, given that IFN-free regimens are imminent. The sustained virological response in F3-4/F0-2 was 71/89% with IFN-based new DAAs, 85/95% with IFN-free regimens, vs. 64/80% with TVR/BOC-based triple therapy. Serious adverse events leading to discontinuation were taken as: 0-0.6% with IFN-based new DAAs, 0% with IFN-free regimens, vs. 1-10% with TVR/BOC-based triple therapy. Costs were €60,000 for 12 weeks of IFN-based new DAAs and two times higher for IFN-free regimens.

    Results

    Treatment with IFN-based new DAAs when fibrosis stage greater than or equal to F2 is cost-effective compared to TVR/BOC-based triple therapy (€37,900/QALY gained), but not at F0-1 (€103,500/QALY gained). Awaiting the IFN-free regimens is more effective, except in F4 patients, but not cost-effective compared to IFN-based new DAAs. If we decrease the cost of IFN-free regimens close to that of IFN-based new DAAs, then awaiting the IFN-free regimen becomes cost-effective.

    Conclusions

    Treatment with IFN-based new DAAs at stage greater than or equal to F2 is both effective and cost-effective compared to TVR/BOC triple therapy. Awaiting IFN-free regimens and then treating regardless of fibrosis is more efficacious, except in F4 patients; however, the cost-effectiveness of this strategy is highly dependent on its cost.

    Abbreviations: G1, genotype 1, HCV, hepatitis C virus, TVR, telaprevir, BOC, boceprevir, DAA, direct-acting antiviral, IFN, interferon, QALYs, quality-adjusted life years, ICER, incremental cost-effectiveness ratio, GDP, gross domestic product, IL28B, interleukin-28B, DRG, diagnosis-related group, SVR, sustained virological response

    Keywords: Boceprevir, Chronic hepatitis C, Cost-effectiveness analysis, Direct-acting antivirals, Genotype 1, Interferon-free regimens, Model-based analysis, Telaprevir, Treatment initiation

    No full text is available. To read the body of this article, please view the PDF online.