In 2013, an estimated 686,000 people died from Hepatitis B infection worldwide. Mass treatment programmes for Hepatitis B will require drugs available at very low costs. International treatment guidelines recommend first-line monotherapy with either entecavir or tenofovir. While the basic patent on tenofovir expires in 2017/8, entecavir is already available as a generic drug in several countries, including the US. The chemical structure of entecavir is closely related to abacavir, which costs < US$200 per person-year in low-income countries at the dose of 600 mg OD (once daily), versus 0.5 mg OD for entecavir.

The authors investigated the clinical efficacy, chemical structures, daily doses, routes of chemical synthesis, costs of raw materials and patent expiry dates for entecavir and tenofovir. Costs of sustainable generics production were calculated for entecavir and compared with published originator and generics prices worldwide. Target prices assumed at least five million people with chronic Hepatitis B treated worldwide (less than 3% of worldwide Hepatitis B epidemic).

The originator product, Bristol-Myers Squibb’s (BMS) Baraclude (entecavir), had an estimated market size of US$294 million for the 12 months ending June 2015 according to IMS [2].

Results
With a daily dose of 0.5 mg, one year’s supply of entecavir treatment requires 0.18 g of Active Pharmaceutical Ingredient (API) per person, estimated to cost US$4 per year, based on quotations of API production from generics suppliers. With an additional US$20 per year for formulation/packaging and a 50% profit margin, entecavir was estimated to cost a minimum of US$36 per person-year, substantially lower than current originator and generics prices, see Table 1. Entecavir is no longer under patent protection in China, Brazil, South Africa and the US, with European expiry in 2017. Given differences in daily dosing, production volumes for entecavir would be 600 times lower than tenofovir DF (300 mg OD), offering significant logistical advantages.

Table 1: Price of entecavir per person-year (US$)

The authors concluded that mass treatment for Hepatitis B with generic entecavir could be achieved with very low costs (minimum US$36 per person-year) in high-, middle- and low-income countries. There would be no patent restrictions to mass generic production of entecavir in most countries. However, these low prices can only be achieved if volume demand increases to at least five million people treated with entecavir worldwide. Use of entecavir could enable patients to avoid the renal and bone toxicities from long-term use of tenofovir, which is also still patented in many countries.

Abstracted by Andrew Hill, Senior Visiting Research Fellow of the Department of Pharmacology and Therapeutics, University of Liverpool, UK.

Conflict of interest
The authors of the research paper [1] declared that there were no conflicts of interest.

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References
1. Hill A, Simmons B, Gotham D, Fortunak J. Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C. J Virus Erad. 2016;2:28-31.
2. GaBI Online – Generics and Biosimilars Initiative. US FDA approval for Hep B and osteoporosis generics [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Mar 25]. Available from: www.gabionline.net/Generics/News/US-FDA-approval-for-Hep-B-and-osteoporosis-generics

Source: www.gabionline.net