According to the California Technology Assessment Forum, a panel of academic pharmacoeconomic experts, representatives of managed care organizations, and advocates for people with hepatitis, a 46% discount would bring the average price of treatment to about $40,000, at which price sofosbuvir-based treatment regimens represent a "high value" for people and healthcare systems.Because of sofosbuvirs high price in the United States, by 2017, some states—such as Louisiana—were withholding the medicine from Medicaid patients with hepatitis until their livers were severely damaged. This puts "patients at increased risk of medical complications" and contributes to the "transmission of the hepatitis C virus". In an article published in May 2016 in Health Affairs, the authors proposed the invocation of the federal "government patent use" law which would enable the government to procure "important patent-protected" drugs at lower prices while compensating "the patent-holding companies reasonable royalties ... for research and development." By July 2017, Louisianas health secretary Rebekah Gee, who described Louisiana as Americas "public-health-crisis cradle", was investigating the use of the "government patent use" as a strategy. Japan and South Korea
Unlike other comparable Western developed countries, sofosbuvir is far more affordable in Japan and South Korea at approximately $300 and $2165 cost to patients respectively for a 12-week treatment, as each government covers 99% and 70% of the original cost respectively. Germany
In Germany, negotiations between Gilead and health insurers led to a price of €41,000 for 12 weeks of treatment.
GS-461203 serves as a defective substrate for the NS5B protein, which is the viral RNA polymerase, thus acts as an inhibitor of viral RNA synthesis. Although sofosbuvir has a 3 hydroxyl group to act as a nucleophile for an incoming NTP, a similar nucleotide analogue, 2-deoxy-2-α-fluoro-β-C-methylcytidine, is proposed to act as a chain terminator because the 2 methyl group of the nucleotide analogue causes a steric clash with an incoming NTP. Sofosbuvir would act in a similar way. Pharmacokinetics
Sofosbuvir is only administered orally. The peak concentration after oral administration is 0.5–2 hours post-dose, regardless of initial dose. Peak plasma concentration of the main circulating metabolite GS-331077 occurs 2–4 hours post-dose. GS-331077 is the pharmacologically inactive nucleoside.Plasma protein binding of sofosbuvir is 61–65%, while GS-331077 has minimal binding.Sofosbuvir is activated in the liver to the triphosphate GS-461203 by hydrolysis of the carboxylate ester by either of the enzymes cathepsin A or carboxylesterase 1, followed by cleaving of the phosphoramidate by the enzyme histidine triad nucleotide-binding protein 1 (HINT1), and subsequent repeated phosphorylation. Dephosphorylation creates the inactive metabolite GS-331077. The half life of sofosbuvir is 0.4 hours, and the half life of GS-331077 is 27 hours.Following a single 400 mg oral dose of sofosbuvir, 80% is excreted in urine, 14% in feces, and 2.5% in expired air recovery. However, of the urine recovery 78% was the metabolite (GS-331077) and 3.5% was sofosbuvir. Chemistry
Prior to the discovery of sofosbuvir, a variety of nucleoside analogs had been examined as antihepatitis C treatments, but these exhibited relatively low potency.