title: Analysis of minimum target prices for production of entecavir to treat hepatitis B in high- and low-income countries.
abstract: BACKGROUND
  In 2013, an estimated 686,000 people died from hepatitis B virus (HBV) infection worldwide. Mass treatment programmes for hepatitis B will require very low drug costs. International treatment guidelines recommend first-line monotherapy with either entecavir or tenofovir disoproxil fumarate (TDF). While the basic patent on TDF expires in 2017/8, entecavir is already generic in several countries, including the US. The chemical structure of entecavir is related to abacavir, which costs <$200 per person-year in low-income countries.
  
  
  METHODS
  The clinical efficacy, chemical structures, daily doses, routes of chemical synthesis, costs of raw materials and patent expiry dates were analysed for entecavir and TDF. Costs of sustainable, generic production were calculated for entecavir, and compared with published originator and generic prices in high- and low-income countries.
  
  
  RESULTS
  With a daily dose of 0.5 mg, one year's supply of entecavir treatment requires <0.2 g of active pharmaceutical ingredient (API) per person, estimated to cost $4/year, based on quotations of API production from generic suppliers. With an additional $20 per year for formulation/packaging and a 50% profit margin, entecavir was estimated to cost a minimum of $36/person-year, substantially lower than current originator and generic prices. Entecavir is no longer under patent protection in the USA, China, Brazil and South Africa, with European expiry in 2017. Given differences in daily dosing, production volumes for entecavir would be 600 times lower than TDF (300 mg once daily) for treating the same numbers of patients.
  
  
  CONCLUSIONS
  Mass treatment for hepatitis B with generic entecavir could be achieved at very low cost in all countries, provided that important projections can be met in terms of pricing for the API and finished dosage form.
authors.affiliation: Department of Pharmacology and Therapeutics , Liverpool University , UK .
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.affiliation: Faculty of Medicine , Imperial College London , UK.
authors.forename: Dzintars
authors.initials: D
authors.lastname: Gotham
authors.affiliation: Faculty of Medicine , Imperial College London , UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Cooke
authors.affiliation: Department of Infectious Diseases/HIV Medicine , Royal Free Hospital , London , UK .
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bhagani
authors.affiliation: Division of Infectious Diseases , Geneva University Hospital , Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Andrieux-Meyer
authors.affiliation: Division of Infectious Diseases , University of Pennsylvania , Philadelphia , USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cohn
authors.affiliation: Chemistry and Pharmaceutical Sciences , Howard University , Washington DC , USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fortunak
keywords: entecavir; hepatitis B; lamivudine; tenofovir