title: Minimum costs for producing hepatitis C direct-acting antivirals for use in large-scale treatment access programs in developing countries.
abstract: BACKGROUND
  Several combinations of 2 or 3 direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naive patients. DAAs for HCV infection have similar mechanisms of action and chemical structures to antiretrovirals for human immunodeficiency virus (HIV) infection. Generic antiretrovirals are currently manufactured at very low prices, to treat 10 million people with HIV/AIDS in developing countries.
  
  
  METHODS
  Four HCV DAAs, currently either in phase 3 development or recent approval (daclatasvir, sofosbuvir, simeprevir, faldaprevir), and ribavirin were classified by chemical structure, molecular weight, total daily dose, and complexity of synthesis. The likely range of manufacturing costs per gram of DAA were then projected as formulated product cost, based upon treating a minimum of 1 million patients annually (to arrive at volume demand) combined with an analysis of the complexity of synthesis and a 40% margin for formulation. Projections were then compared with actual costs of antiretrovirals with similar structures.
  
  
  RESULTS
  Minimum manufacturing costs of antiretrovirals were US$0.2-$2.1 per gram. The complexity of chemical synthesis for HCV DAAs was ranked from lowest to highest: ribavirin, daclatasvir, sofosbuvir, faldaprevir, and simeprevir. Predicted manufacturing costs (US dollars) for 12-week courses of HCV DAAs were $21-$63 for ribavirin, $10-$30 for daclatasvir, $68-$136 for sofosbuvir, $100-$210 for faldaprevir, and $130-$270 for simeprevir.
  
  
  CONCLUSIONS
  Within the next 15 years, large-scale manufacture of 2 or 3 drug combinations of HCV DAAs is feasible, with minimum target prices of $100-$250 per 12-week treatment course. These low prices could make widespread access to HCV treatment in low- and middle-income countries a realistic goal.
authors.affiliation: Department of Pharmacology and Therapeutics, Liverpool University, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.forename: Joe
authors.initials: J
authors.lastname: Fortunak
authors.forename: Bryony
authors.initials: B
authors.lastname: Simmons
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
mesh_terms: D000621:Aminoisobutyric Acids; D019380:Anti-HIV Agents / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry / Q000191:economics* / Q000627:therapeutic use; D002219:Carbamates; D003906:Developing Countries; D004345:Drug Industry / Q000191:economics; D004359:Drug Therapy, Combination; D006297:Health Services Accessibility / Q000191:economics; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000191:economics / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000191:economics / Q000627:therapeutic use; D007930:Leucine / Q000031:analogs & derivatives; D009842:Oligopeptides / Q000737:chemistry / Q000191:economics / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives; D011759:Pyrrolidines; D011804:Quinolines; D012254:Ribavirin / Q000737:chemistry / Q000191:economics / Q000627:therapeutic use; D000069616:Simeprevir; D000069474:Sofosbuvir; D013449:Sulfonamides / Q000737:chemistry / Q000191:economics / Q000627:therapeutic use; D013844:Thiazoles / Q000737:chemistry / Q000191:economics / Q000627:therapeutic use; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000191:economics / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000621:Aminoisobutyric Acids; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D002219:Carbamates; D006575:Heterocyclic Compounds, 3-Ring; D007093:Imidazoles; D009842:Oligopeptides; D011759:Pyrrolidines; D011804:Quinolines; D013449:Sulfonamides; D013844:Thiazoles; D012254:Ribavirin; C552340:faldaprevir; D011392:Proline; D000069616:Simeprevir; D014542:Uridine Monophosphate; D007930:Leucine; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
keywords: daclatasvir; faldaprevir; ribavirin; simeprevir; sofosbuvir