Minimum costs for producing hepatitis C direct-acting antivirals for use in large-scale treatment access programs in developing countries

Clin Infect Dis. 2014 Apr;58(7):928-36. doi: 10.1093/cid/ciu012. Epub 2014 Jan 6.

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.

Keywords: daclatasvir; faldaprevir; ribavirin; simeprevir; sofosbuvir.

MeSH terms

  • Aminoisobutyric Acids
  • Anti-HIV Agents / chemistry
  • Antiviral Agents / chemistry
  • Antiviral Agents / economics*
  • Antiviral Agents / therapeutic use
  • Carbamates
  • Developing Countries*
  • Drug Industry / economics
  • Drug Therapy, Combination
  • Health Services Accessibility / economics
  • Hepacivirus
  • Hepatitis C / drug therapy
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Heterocyclic Compounds, 3-Ring / economics
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / economics
  • Imidazoles / therapeutic use
  • Leucine / analogs & derivatives
  • Oligopeptides / chemistry
  • Oligopeptides / economics
  • Oligopeptides / therapeutic use
  • Proline / analogs & derivatives
  • Pyrrolidines
  • Quinolines
  • Ribavirin / chemistry
  • Ribavirin / economics
  • Ribavirin / therapeutic use
  • Simeprevir
  • Sofosbuvir
  • Sulfonamides / chemistry
  • Sulfonamides / economics
  • Sulfonamides / therapeutic use
  • Thiazoles / chemistry
  • Thiazoles / economics
  • Thiazoles / therapeutic use
  • Uridine Monophosphate / analogs & derivatives
  • Uridine Monophosphate / chemistry
  • Uridine Monophosphate / economics
  • Uridine Monophosphate / therapeutic use
  • Valine / analogs & derivatives

Substances

  • Aminoisobutyric Acids
  • Anti-HIV Agents
  • Antiviral Agents
  • Carbamates
  • Heterocyclic Compounds, 3-Ring
  • Imidazoles
  • Oligopeptides
  • Pyrrolidines
  • Quinolines
  • Sulfonamides
  • Thiazoles
  • Ribavirin
  • faldaprevir
  • Proline
  • Simeprevir
  • Uridine Monophosphate
  • Leucine
  • Valine
  • daclatasvir
  • Sofosbuvir