Provided by NATAP
Reported by Jules Levin
64th Annual Meeting of AASLD, Washington DC, United States of America, November 2013 [Poster 1097]
Andrew Hill and Saye Khoo, Department of Pharmacology and Therapeutics, Liverpool University, UK
Bryony Simmons, Imperial College, London, UK
Nathan Ford, University of Cape Town, South Africa
(Click on images to enlarge)
Ribavirin (generic) is a nucleoside analogue, with a relatively simple chemical synthesis (conversion factor (CF) x1). The daily dose is 1000-1200mg, with an overall dose of 84-100g for 12 weeks of treatment. Production costs were estimated at $0.25 to $0.75 per gram, giving an estimated cost of $21 to $76 for a 12 week course of treatment.
Daclatasvir (patent expiry 2027) is an NS5A inhibitor, and has a straightforward synthesis given its symmetry and the availability of cheap starting materials to synthesise the side-chains (CF x1-3). The daily dose is 60mg, with a total dose of 5g for 12 weeks of treatment. Production costs were estimated conservatively at $2 to $6 per gram, giving an estimated cost of $10 to $30 for a 12 week course of treatment.
Sofosbuvir (patent expiry 2029) is a nucleotide which requires a 2'-fluro-2'-methylfuranose intermediate. This cost-limiting material complicates synthesis (CF x4). The daily dose is 400mg, with a total dose of 34g for 12 weeks of treatment. Production costs were estimated at $2 to $4 per gram, giving an estimated cost of $68 to $136 for 12 weeks of treatment.
Faldaprevir (patent expiry 2025) is a protease inhibitor which requires a tetra-substituted quinoline and a vinyl-cyclopropane amino acid : this complicates the chemical synthesis (CF x10). The daily dose is 120mg, with a total dose of 10g for 12 weeks of treatment. Production costs were estimated at $10 to $21 per gram, giving an estimated cost of $100 to $210 for 12 weeks of treatment.
Simeprevir (patent expiry 2026) , a protease inhibitor, is a medium-ring macrocycle that utilises a novel, ring-closing metathesis reaction in the late stages of API manufacturing. Novel raw material include a tetra-substituted quinoline and a vinyl-cyclopropane amino acid: this significantly complicates synthesis (CF x10). The daily dose is 150mg, with a total dose of 13g for 12 weeks of treatment. Production costs were estimated at $10 to $21 per gram, giving an estimated cost of $130 to $270 for 12 weeks of treatment.
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