Sofosbuvir approved in the US and Europe for HCV genotypes 1-6

1 February 2014. Related: Hepatitis coinfection.

Simon Collins, HIV i-Base

On 17 January 2014, the EU approved sofosbuvir, a new oral treatment for chronic hepatitis C (CHC) in adults. This indication specifically includes use by people with HCV and HIV coinfection. [1]

Sofosbuvir is a once-daily (400 mg) oral nucleotide analogue polymerase inhibitor that needs to be used in combination with other antiviral drugs (ribavirin (RBV) and pegylated interferon alpha (peg-IFN) depending on hepatitis C (HCV) genotype.

This will allow shorter treatment durations and interferon-free combinations for some patients (see Tables 1 and 2.)

• Sofosbuvir monotherapy is not recommended.
• Treatment regimen and duration are dependent on both viral genotype and patient population
• Treatment response varies based on baseline host and viral factors.

Sofosbuvir was approved in the US on 6 December 2013.

Sofosbuvir is manufactured by Gilead Sciences and is marketed under the trade name Sovaldi.

For full details, see the EU and US Summary of Product Characteristics. [3, 4]

Notes: See prescribing information for dosing recommendation for PEG-IFN for patients with genotype 1 or 4 CHC.
 Dose of ribavirin is weight-based (<75 kg = 1000 mg and ≥75 kg = 1200 mg). The daily dose of ribavirin is administered orally in two divided doses with food. Patients with renal impairment (CrCl ≤ 50 mL/min) require ribavirin dose reduction; refer to ribavirin prescribing information.

Comment

Better and more effective treatments could make hepatitis C curable for most people with just three months of oral medication. Whether this impacts the global burden of disease – and an estimated 185 million people have hepatitis C – will depend on access to treatment and this will be determined by the price.

Sofosbuvir in the US will cost $84,000 for a three-month course or roughly $1000 a day – and some people need six months. This has been the focus of much of the news coverage in the US, both from treatment activists and in mainstream reports. [5, 6, 7]

The price was apparently calculated, not based on research and development costs – or even acquisition costs (Gilead paid paid $11 billion to purchase Pharmasset in November 2011). [8] Instead, it is being justified on the potential savings to the healthcare system for future years of therapy, hospitalisations, transplants and other healthcare costs that will be avoided. This model is based on the assumption that everyone enters the healthcare system, but people also have the option to be excluded from care or to die beforehand. The model also depends on paying these estimated lifetime costs up-front now.

Premium pricing is no longer an acceptable model for bringing new drugs to market. Just as in HIV care, new HCV drugs should be matched to current treatment costs. The premium should come from greater use due to their better efficacy and tolerability. If the actual costs are cheaper then treatment costs should come down. The estimated manufacturing costs for sofosbuvir may be as little as a few hundred dollars. [9]

If the new direct acting antivirals (DAAs) in Europe are set at similar prices to sofosbuvir in the US this will result in treatment rationing and limit access in the UK to use as a salvage therapy for people who have to first fail pegylated interferon and ribavirin. Currently in the UK, only 3% of the estimated 230,000 people living with HCV are treated each year.

In the US, even if only one third of the 3-4 million people with HCV have health insurance, Gilead could largely recoup the acquisition costs if the price was $10,000. For many activists, including George Carter writing for thebody.com, this is still excessive. [7]

This is an area where patient demand should drive the solution. At least for people with genotype 1, oral only treatment should rapidly become the standard of care. Profits need to be calculated from the broadest distribution and access.

Globally, access is just as urgently needed in lower and middle-income countries, accounting for 90% of people with living with HCV. Similar strategies to those that enabled global access to ARVs need to be developed, including working with generic manufacturers and collaborations such as UNITAID and the Patent Pool.

References:

1. Gilead press statement. European Commission grants marketing authorization for Gilead’s Sovaldi (sofosbuvir) for the treatment of chronic hepatitis C infection. (17 January 2014).
   http://www.gilead.com/news/press-releases
2. US FDA. FDA approves Sovaldi for chronic hepatitis C. (06 December 2013).
   http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm377888.htm
3. Sofosbuvir Summary of Product Characteristics (Europe).
   http://www.ema.europa.eu
4. Sofosbuvir Summary of Product Characteristics (US).
   http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm377920.htm
5. FPC press statement. Fair Pricing Coalition condemns Gilead Sciences on the high price of new hepatitis C drug Sovaldi, and urges rapid and wide dissemination of support program details for uninsured and underinsured people living with hepatitis C. (11 December 2013).
   http://fairpricingcoalition.org/2013/12/11/fair-pricing-coalition-condemns-gilead-sciences
6. Armstrong J. At $84,000 Gilead hepatitis C drug sets off payer revolt. Bloomberg Market News. (27 January 2014).
   http://mobile.bloomberg.com/news/2014-01-27/at-84-000-gilead-hepatitis-c-drug-sets-off-payer-revolt.html
7. Carter G. The cure for hepatitis C, witheld. Thebody.com. (15 December 2013)
   http://www.thebody.com/content/73501/the-cure-for-hepatitis-c-withheld.html
8. HIV Treatment Bulletin (HTB). New formulations, acquisitions and company announcements. December 2011.
   https://i-base.info/htb/15925
9. Hill A et al. What is the minimum cost per person to cure HCV? 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 30 June – 3 July 2013, Kuala Lumpur. Late breaker poster TULBPE16.
   http://pag.ias2013.org/abstracts.aspx?aid=3142
   http://pag.ias2013.org/EPosterHandler.axd?aid=3142 (Poster PDF)