Minimum costs for producing hepatitis C direct-acting antivirals for use in large-scale treatment access programs in developing countries
Author(s)
Hill, Andrew
Khoo, Saye
Fortunak, Joe
Simmons, Bryony
Ford, Nathan
Type
Journal Article
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.
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.
Date Issued
2014-04-01
Date Acceptance
2013-12-28
Citation
Clinical Infectious Diseases, 2014, 58 (7), pp.928-936
ISSN
1058-4838
Publisher
Oxford University Press (OUP)
Start Page
928
End Page
936
Journal / Book Title
Clinical Infectious Diseases
Volume
58
Issue
7
Copyright Statement
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000333055400005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
sofosbuvir
daclatasvir
ribavirin
simeprevir
faldaprevir
ANTIRETROVIRAL TREATMENT
BI 201335
INHIBITOR
HIV
SOFOSBUVIR
RIBAVIRIN
POTENT
Publication Status
Published
Date Publish Online
2014-01-06