Sofosbuvir: Difference between revisions

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Common side effects include fatigue, headache, nausea, and trouble sleeping.<ref name=AHFS2016/> Side effects are generally more common in interferon-containing regimens.<ref name="Sovaldi FDA label">{{cite web | title=Sovaldi- sofosbuvir tablet, film coated Sovaldi- sofosbuvir pellet | website=DailyMed | date=27 September 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=80beab2c-396e-4a37-a4dc-40fdb62859cf | access-date=4 February 2020}}</ref>{{rp|7}} Sofosbuvir may reactivate [[hepatitis B]] in those who have been previously infected.<ref name=FDAwarning2016>{{cite web|title=Direct-Acting Antivirals for Hepatitis C: Drug Safety Communication - Risk of Hepatitis B Reactivating|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm523690.htm|website=FDA|access-date=6 October 2016|date=4 October 2016|url-status=dead|archive-url=https://web.archive.org/web/20161006160327/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm523690.htm|archive-date=6 October 2016 }}</ref> In combination with [[ledipasvir]], [[daclatasvir]] or [[simeprevir]], it is not recommended with [[amiodarone]] due to the risk of an [[bradycardia|abnormally slow heartbeat]].<ref name="Sovaldi FDA label"/> Sofosbuvir is in the [[nucleotide analog]] family of medications and works by blocking the hepatitis C [[NS5B]] protein.<ref name=UKlabel>{{cite web|title=Sovaldi 400 mg film coated tablets - Summary of Product Characteristics|url=https://www.medicines.org.uk/emc/medicine/28539|publisher=UK Electronic Medicines Compendium|access-date=10 November 2016|date=September 2016|url-status=live|archive-url=https://web.archive.org/web/20161110235042/https://www.medicines.org.uk/emc/medicine/28539|archive-date=10 November 2016 }}</ref>

Sofosbuvir was discovered in 2007 and approved for medical use in the United States in 2013.<ref name="Sovaldi FDA label"/><ref name=UW2017>{{cite web|title=Sofosbuvir (Sovaldi) - Treatment - Hepatitis C Online|url=http://www.hepatitisc.uw.edu/page/treatment/drugs/sofosbuvir-drug|website=www.hepatitisc.uw.edu|access-date=8 January 2017 |url-status=live |archive-url=https://web.archive.org/web/20161223152415/http://www.hepatitisc.uw.edu/page/treatment/drugs/sofosbuvir-drug|archive-date=23 December 2016 }}</ref><ref name=NewYorker>{{cite magazine|last1 vauthors = Gounder|first1=Celine C |title=A Better Treatment for Hepatitis C|url=http://www.newyorker.com/tech/elements/a-better-treatment-for-hepatitis-c|magazine=[[The New Yorker]]|date=9 December 2013|url-status=live|archive-url=https://web.archive.org/web/20160920171440/http://www.newyorker.com/tech/elements/a-better-treatment-for-hepatitis-c|archive-date=20 September 2016 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref>

Compared to previous treatments, sofosbuvir-based regimens provide a higher cure rate, fewer side effects, and a two- to four-fold reduction in therapy duration.<ref name=dutch2014>{{cite journal | vauthors = Berden FA, Kievit W, Baak LC, Bakker CM, Beuers U, Boucher CA, Brouwer JT, Burger DM, van Erpecum KJ, van Hoek B, Hoepelman AI, Honkoop P, Kerbert-Dreteler MJ, de Knegt RJ, Koek GH, van Nieuwkerk CM, van Soest H, Tan AC, Vrolijk JM, Drenth JP | display-authors = 6 | title = Dutch guidance for the treatment of chronic hepatitis C virus infection in a new therapeutic era | journal = The Netherlands Journal of Medicine | volume = 72 | issue = 8 | pages = 388–400 | date = October 2014 | pmid = 25387551 }}</ref><ref>{{cite journal | vauthors = Cholongitas E, Papatheodoridis GV | title = Sofosbuvir: a novel oral agent for chronic hepatitis C | journal = Annals of Gastroenterology | volume = 27 | issue = 4 | pages = 331–337 | year = 2014 | pmid = 25332066 | pmc = 4188929 }}</ref><ref>{{cite journal | vauthors = Tran TT | title = A review of standard and newer treatment strategies in hepatitis C | journal = The American Journal of Managed Care | volume = 18 | issue = 14 Suppl | pages = S340–9S340–S349 | date = December 2012 | pmid = 23327540 }}</ref> Sofosbuvir allows most people to be treated successfully without the use of peginterferon, an injectable drug with severe side effects that is a key component of older drug combinations for the treatment of hepatitis C virus.<ref name=Yau2014rev>{{cite journal | vauthors = Yau AH, Yoshida EM | title = Hepatitis C drugs: the end of the pegylated interferon era and the emergence of all-oral interferon-free antiviral regimens: a concise review | journal = Canadian Journal of Gastroenterology & Hepatology | volume = 28 | issue = 8 | pages = 445–51445–451 | date = September 2014 | pmid = 25229466 | pmc = 4210236 | doi = 10.1155/2014/549624 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Calvaruso V, Mazza M, Almasio PL | title = Pegylated-interferon-α(2a) in clinical practice: how to manage patients suffering from side effects | journal = Expert Opinion on Drug Safety | volume = 10 | issue = 3 | pages = 429–35429–435 | date = May 2011 | pmid = 21323500 | doi = 10.1517/14740338.2011.559161 | hdl-access = 10447/73456free | s2cid = 207487328 | hdl-access = free10447/73456 }}</ref>

Sofosbuvir used alone and in combination with other drugs such as [[ribavirin]] with or without a peginterferon has a good safety profile. Common side effects are fatigue, headache, nausea, rash, irritability, dizziness, back pain, and anemia. Most side effects are more common in interferon-containing regimens as compared to interferon-free regimens. For example, fatigue and headache are nearly reduced by half, influenza-like symptoms are reduced to 3–6% as compared to 16–18%, and [[neutropenia]] is almost absent in interferon-free treatment.<ref name="Sovaldi FDA label"/>{{rp|7}}<ref>{{cite journal | vauthors = Bhatia HK, Singh H, Grewal N, Natt NK | title = Sofosbuvir: A novel treatment option for chronic hepatitis C infection | journal = Journal of Pharmacology & Pharmacotherapeutics | volume = 5 | issue = 4 | pages = 278–84278–284 | date = October 2014 | pmid = 25422576 | pmc = 4231565 | doi = 10.4103/0976-500X.142464 | doi-access = free }}</ref>

Sofosbuvir may reactivate hepatitis B in those who have been previously infected.<ref name=FDAwarning2016/> The [[European Medicines Agency]] (EMA) has recommended screening all people for hepatitis B before starting sofosbuvir for hepatitis C in order to minimize the risk of hepatitis B reactivation.<ref>{{cite web | title=Direct-acting antivirals indicated for treatment of hepatitis C (interferon-free) | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/referrals/direct-acting-antivirals-indicated-treatment-hepatitis-c-interferon-free | access-date=4 February 2020}}</ref>

Sofosbuvir inhibits the hepatitis C [[NS5B]] protein.<ref name=UKlabel/> Sofosbuvir appears to have a high barrier to the development of resistance.<ref>{{cite journal | vauthors = Pol S, Corouge M, Vallet-Pichard A | title = Daclatasvir-sofosbuvir combination therapy with or without ribavirin for hepatitis C virus infection: from the clinical trials to real life | journal = Hepatic Medicine: Evidence and Research| volume = 8 | pages = 21–621–26 | date = March 2016 | pmid = 27019602 | pmc = 4786064 | doi = 10.2147/HMER.S62014 | doi-access = free }}</ref>

Sofosbuvir is a [[prodrug]] of the [[Protide]] type, whereby the active phosphorylated nucleotide is granted cell permeability and oral bioavailability. It is metabolized to the active antiviral agent GS-461203 (2'-deoxy-2'-α-fluoro-β-''C''-methyluridine-5'-triphosphate). 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.<ref>{{cite journal | vauthors = Fung A, Jin Z, Dyatkina N, Wang G, Beigelman L, Deval J | title = Efficiency of incorporation and chain termination determines the inhibition potency of 2'-modified nucleotide analogs against hepatitis C virus polymerase | journal = Antimicrobial Agents and Chemotherapy | volume = 58 | issue = 7 | pages = 3636–453636–3645 | date = July 2014 | pmid = 24733478 | pmc = 4068585 | doi = 10.1128/AAC.02666-14 }}</ref> 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.<ref>{{cite journal | vauthors = Ma H, Jiang WR, Robledo N, Leveque V, Ali S, Lara-Jaime T, Masjedizadeh M, Smith DB, Cammack N, Klumpp K, Symons J | display-authors = 6 | title = Characterization of the metabolic activation of hepatitis C virus nucleoside inhibitor beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) and identification of a novel active 5'-triphosphate species | journal = The Journal of Biological Chemistry | volume = 282 | issue = 41 | pages = 29812–2029812–29820 | date = October 2007 | pmid = 17698842 | doi = 10.1074/jbc.M705274200 | doi-access = free }}</ref> Sofosbuvir wouldmay act in a similar way.{{cn|date=November 2022}}

Sofosbuvir is only administered orally. The peak concentration after oral administration is 0.5–2 hours post-dose, regardless of initial dose.<ref name=KirbyPKrev2015>{{cite journal | vauthors = Kirby BJ, Symonds WT, Kearney BP, Mathias AA | title = Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of the Hepatitis C Virus NS5B Polymerase Inhibitor Sofosbuvir | journal = Clinical Pharmacokinetics | volume = 54 | issue = 7 | pages = 677–90677–690 | date = July 2015 | pmid = 25822283 | doi = 10.1007/s40262-015-0261-7 | s2cid = 20488837 }}</ref> Peak plasma concentration of the main circulating metabolite GS-331077 occurs 2–4 hours post-dose.<ref name=KirbyPKrev2015/> GS-331077 is the pharmacologically inactive [[nucleoside]].<ref name="Sovaldi FDA label"/>

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]].<ref>{{cite book|title=Arzneistoff-Profile| veditors = Dinnendahl V, Fricke U | publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|date=2015|edition=28|volume=9|isbn=978-3-7741-9846-3|language=de}}</ref> [[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.<ref name="Sovaldi FDA label"/>Following a single 400&nbsp;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.<ref name=KirbyPKrev2015/>

Prior to the discovery of sofosbuvir, a variety of nucleoside analogs had been examined as antihepatitis C treatments, but these exhibited relatively low potency. This low potency arose in part because the enzymatic addition of the first of the three phosphate groups of the triphosphate is slow. The design of sofosbuvir, based on the [[ProTide]] approach, avoids this slow step by building the first phosphate group into the structure of the drug during synthesis. Additional groups are attached to the phosphorus to temporarily mask the two negative charges of the phosphate group, thereby facilitating entry of the drug into the infected cell.<ref name="pmid20801890">{{cite journal | vauthors = Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA | display-authors = 6 | title = Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977 | journal = The Journal of Biological Chemistry | volume = 285 | issue = 45 | pages = 34337–4734337–34347 | date = November 2010 | pmid = 20801890 | pmc = 2966047 | doi = 10.1074/jbc.M110.161802 | doi-access = free }}</ref> The NS5B protein is a [[RNA-dependent RNA polymerase]] critical for the viral reproduction cycle.{{cn|date=November 2022}}

Sofosbuvir was discovered in 2007 by [[Michael J. Sofia]], a scientist at [[Pharmasset]], and the drug was first tested in people in 2010. In 2011, [[Gilead Sciences]] bought Pharmasset for about $11 billion.<ref name=NewYorker/> Gilead submitted the [[New Drug Application]] for sofosbuvir in combination with [[ribavirin]] in April 2013, and in October 2013 it received the FDA's [[Breakthrough therapy|Breakthrough Therapy Designation]].<ref name=FDAreview>{{cite web|title=Application Number: 204671Orig1s000: Medical Reviews|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204671Orig1s000MedR.pdf|publisher=FDA|date=November 20, 2013|url-status=live|archive-url=https://web.archive.org/web/20161110175252/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204671Orig1s000MedR.pdf|archive-date=November 10, 2016 }}</ref> In December 2013, the [[FDA]] approved sofosbuvir in combination with ribavirin for oral dual therapy of [[Hepatitis C virus#Genotypes|HCV genotypes]] 2 and 3, and for triple therapy with injected [[pegylated interferon]] (pegIFN) and RBV for treatment-naive people with HCV genotypes 1 and 4.<ref name=FDA2013>{{cite web | url = https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm377888.htm | title = FDA approves Sovaldi for chronic hepatitis C | date = 2013-12-06 | work = FDA New Release | publisher = U.S. Food and Drug Administration | url-status = live | archive-url = https://web.archive.org/web/20131209000157/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm377888.htm | archive-date = 2013-12-09 }}</ref><ref name="medscape">{{cite web| url = http://www.medscape.com/viewarticle/817371| title = FDA Approves 'Game Changer' Hepatitis C Drug Sofosbuvir| author = Tucker M| date = December 6, 2013| website = Medscape| url-status = live| archive-url = https://web.archive.org/web/20150517012529/http://www.medscape.com/viewarticle/817371| archive-date = May 17, 2015}}</ref> Two months before, the FDA had approved another drug, [[simeprevir]], as a hepatitis C treatment.<ref name=FDA2013/>

Prior to the availability of sofosbuvir, hepatitis C treatments involved 6 to 12 months of treatment with an interferon-based regimen. This regimen provided cure rates of 70% or less and was associated with severe side effects, including anemia, depression, severe rash, nausea, diarrhea, and fatigue. As sofosbuvir clinical development progressed, physicians began to "warehouse" people in anticipation of its availability.<ref>{{cite news|url=https://www.wsj.com/articles/SB10001424127887323293704578330712442353712|title=Hepatitis C Dilemma: Treat Illness With Interferon Now or Wait? - WSJ|newspaper=Wall Street Journal|date=5 March 2013|url-status=live|archive-url=https://web.archive.org/web/20170602215108/https://www.wsj.com/articles/SB10001424127887323293704578330712442353712|archive-date=2017-06-02 |last1 vauthors = Loftus|first1=Peter P }}</ref> Sofosbuvir's U.S. launch was the fastest of any new drug in history.<ref name=Herper2014>{{cite news|last1 vauthors = Herper|first1=Matthew M |title= Gilead's Hepatitis C Pill Takes Off Like A Rocket|url=https://www.forbes.com/sites/matthewherper/2014/02/21/gileads-hepatitis-c-pill-takes-off-like-a-rocket/|work=Forbes|date=February 21, 2014|url-status=live|archive-url=https://web.archive.org/web/20170831233640/https://www.forbes.com/sites/matthewherper/2014/02/21/gileads-hepatitis-c-pill-takes-off-like-a-rocket/|archive-date=August 31, 2017 }}</ref>

Following its approval by the FDA in 2013,<ref name="FDA2013" /> the price of sofosbuvir as quoted in various media sources in 2014 ranged from $84,000 to $168,000 depending on course of treatment in the U.S.<ref name=NYTprice2014>{{cite news |last1 vauthors = Harris |first1=GardinerG |title=Maker of Costly Hepatitis C Drug Sovaldi Strikes Deal on Generics for Poor Countries |url=https://www.nytimes.com/2014/09/16/business/international/maker-of-hepatitis-c-drug-strikes-deal-on-generics-for-poor-countries.html |work=[[The New York Times]] |date=15 September 2014 |url-status=live |archive-url=https://web.archive.org/web/20170131153408/https://www.nytimes.com/2014/09/16/business/international/maker-of-hepatitis-c-drug-strikes-deal-on-generics-for-poor-countries.html?_r=0 |archive-date=31 January 2017 }}</ref> and £35,000 in the United Kingdom for a 12-week regimine,<ref name=Guardian2015>{{cite news |last1 vauthors = Boseley |first1=SarahS |title=Hepatitis C drug delayed by NHS due to high cost |url=https://www.theguardian.com/society/2015/jan/16/sofosbuvir-hepatitis-c-drug-nhs |work=[[The Guardian]] |date=15 January 2015 |url-status=live |archive-url=https://web.archive.org/web/20161110174558/https://www.theguardian.com/society/2015/jan/16/sofosbuvir-hepatitis-c-drug-nhs |archive-date=10 November 2016 }}</ref> causing considerable controversy.<ref name="Stanton"/><ref name="Waldman"/> Sofosbuvir was more affordable in Japan and South Korea at approximately $300 and $5900 respectively for a 12-week treatment, with each government covering 99% and 70% of the cost respectively.<ref name="view.asiae.co.kr"/><ref name="edaily.co.kr"/> In 2014, Gilead announced it would work with generic manufacturers in 91 developing countries to produce and sell sofosbuvir, and that it would sell a name brand version of the product in [[India]] for approximately $300 per course of treatment; it had signed agreements with generic manufacturers by September 2015.<ref name=Prices2014>{{cite journal | vauthors = van de Ven N, Fortunak J, Simmons B, Ford N, Cooke GS, Khoo S, Hill A | title = Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus | journal = Hepatology | volume = 61 | issue = 4 | pages = 1174–821174–1182 | date = April 2015 | pmid = 25482139 | pmc = 4403972 | doi = 10.1002/hep.27641 }}</ref><ref name=ReutersIndia2015>{{cite news |last1=Kalra |first1=Adityavauthors |last2=Siddiqui |first2=ZebaKalra |A, name-list-style =Siddiqui vancZ |title=Gilead licenses hepatitis C drug to Cipla, Ranbaxy, five others|url=http://in.reuters.com/article/gilead-sciences-india-idINKBN0HA0TI20140915 |publisher=Reuters India |date=September 15, 2014 |url-status=livedead |archive-url=https://web.archive.org/web/20141210072017/http://in.reuters.com/article/2014/09/15/gilead-sciences-india-idINKBN0HA0TI20140915 |archive-date=December 10, 2014 }}</ref>

Since its launch, the price of sofosbuvir declined as more competitors entered the [[Direct-acting antivirals|direct-acting antiviral]] (DAA) market.<ref>{{Citecite web|title=Analysis of prescription drugs for the treatment of hepatitis C in the United States|url=https://www.milliman.com/en/insight/analysis-of-prescription-drugs-for-the-treatment-of-hepatitis-c-in-the-united-states|access-date=2022-02-04|website=www.milliman.com|language=en}}</ref> In 2020, the price for a course of sofosbuvir was $64,693 in the United States.<ref name=":0">{{Citecite journal |last1 vauthors = Barber|first1=Melissa J.|last2=MJ, Gotham|first2=Dzintars|last3= D, Khwairakpam|first3=Giten|last4= G, Hill A |first4=Andrew|date=2020-09-01| title = Price of a hepatitis C cure: Cost of production and current prices for direct-acting antivirals in 50 countries | journal = Journal of Virus Eradication |language=en| volume = 6 | issue = 3 | pages = 100001 | date = September 2020 | pmid = 33251019 | pmc = 7646676 | doi = 10.1016/j.jve.2020.06.001|pmid=33251019|pmc=7646676|issn=2055-6640 }}</ref> In 2014, the list price of a 12-week combination treatment with a sofosbuvir-based regimen ranged from {{currency|84000|US}} to $94,000.<ref>{{Citecite news |first vauthors =Andrew |last=Pollack | name-list-style = vancA |url=https://www.nytimes.com/2014/10/11/business/harvoni-a-hepatitis-c-drug-from-gilead-wins-fda-approval.html |title=Harvoni, a Hepatitis C Drug from Gilead, Wins F.D.A. Approval |date=October 10, 2014 |work= [[The New York Times]] |url-status=live |archive-url=https://web.archive.org/web/20170126220951/https://www.nytimes.com/2014/10/11/business/harvoni-a-hepatitis-c-drug-from-gilead-wins-fda-approval.html |archive-date=January 26, 2017 }}</ref><ref name="ap122014">{{cite news |agency=[[Associated Press]] |date=December 11, 2014 |title=Gilead Faces Lawsuit Over Hepatitis C Drug Pricing |work=Drug Discovery & Development |publisher=Advantage Business Media |url=http://www.dddmag.com/news/2014/12/gilead-faces-lawsuit-over-hepatitis-c-drug-pricing |url-status=live |archive-url=https://web.archive.org/web/20141213080109/http://www.dddmag.com/news/2014/12/gilead-faces-lawsuit-over-hepatitis-c-drug-pricing |archive-date=December 13, 2014 }}</ref><ref name="NYTimes. com">{{cite web |title=F. D. A. Approves Pill to Treat Hepatitis |url=https://www.nytimes.com/2013/12/07/business/fda-approves-pill-to-treat-hepatitis-c.html | lastvauthors = Pollack | first = Andrew | name-list-style = vancA |date=December 6, 2013 |work=[[The New York Times]] |url-status=live |archive-url=https://web.archive.org/web/20170203145754/http://www.nytimes.com/2013/12/07/business/fda-approves-pill-to-treat-hepatitis-c.html |archive-date=February 3, 2017 }}</ref> In April 2014, U.S. House Democrats Henry Waxman, [[Frank Pallone]] Jr., and [[Diana DeGette]] wrote Gilead Sciences Inc. questioning the $84,000 price for sofosbuvir. They specifically asked Gilead CEO [[John C. Martin (businessman)|John Martin]] to "explain how the drug was priced, what discounts are being made available to low-income patients and government health programs, and the potential impact to public health by insurers blocking or delaying access to the medicine because of its cost."<ref name="bloomberg_2014">{{cite web |url=https://www.bloomberg.com/news/articles/2014-03-21/gilead-s-84-000-treatment-questioned-by-congress |title=Gilead's $84,000 Treatment Questioned by U.S. Lawmakers |publisher=Bloomberg |date=21 March 2014 |access-date=27 October 2015 |last=Armstrong |firstvauthors =Drew |Armstrong name-list-style = vancD | url-status=live |archive-url=https://web.archive.org/web/20151208203321/http://www.bloomberg.com/news/articles/2014-03-21/gilead-s-84-000-treatment-questioned-by-congress |archive-date=8 December 2015 }}</ref> Sofosbuvir is cited as an example of how specialty drugs present both benefits and challenges.<ref name="bloomberg_2014" /><ref name="pppmag_2015">{{cite web |url=http://www.pppmag.com/article_print.php?articleid=1637 |title=The Increasing Impact of High-Cost Specialty Therapies |volume=12 |number=2 |date=February 2015 |work=Pharmacy Purchasing & Products |access-date=4 December 2015 |last=Lucio |firstvauthors =Steven |Lucio name-list-style = vancS |url-status=dead |archive-url= https://web.archive.org/web/20151208051829/http://www.pppmag.com/article_print.php?articleid=1637 |archive-date=8 December 2015 }}</ref><ref name="JAMA">{{cite journal | vauthors = Brennan T, Shrank W | title = New expensive treatments for hepatitis C infection | journal = JAMA | volume = 312 | issue = 6 | pages = 593–4593–594 | date = August 2014 | pmid = 25038617 | doi = 10.1001/jama.2014.8897 }}</ref>

In February 2015, Gilead announced that due in part to negotiated discounts with pharmacy benefit managers and legally mandated discounts to government payers, the average discount-to-list price in 2014 was 22%. The company estimated that the average discount in 2015 would be 46%.<ref name="Martin_2014">{{cite web |url=http://seekingalpha.com/article/2880996-gilead-sciences-gild-ceo-john-martin-on-q4-2014-results-earnings-call-transcript?page=4 |title=Gilead Q4 2014 Earnings Call |date=3 February 2015 |url-status=live |archive-url=https://web.archive.org/web/20150222163149/http://seekingalpha.com/article/2880996-gilead-sciences-gild-ceo-john-martin-on-q4-2014-results-earnings-call-transcript?page=4 |archive-date=2015-02-22 }}</ref> 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.<ref>{{cite press release |url=http://www.ctaf.org/about-ctaf/news/2015/new-lower-prices-gilead-hepatitis-c-drugs-reach-ctaf-threshold-high-health |title=New Lower Prices for Gilead Hepatitis C Drugs Reach CTAF Threshold for High Health System Value |date=2015-02-17 |access-date=2015-02-22 |url-status=live |archive-url=https://web.archive.org/web/20150222163142/http://www.ctaf.org/about-ctaf/news/2015/new-lower-prices-gilead-hepatitis-c-drugs-reach-ctaf-threshold-high-health |archive-date=2015-02-22 }}</ref><ref>{{Citecite web| title = Treatments for Hepatitis C| author = California Technology Assessment Forum| date = 2014-03-10| url = http://www.ctaf.org/reports/treatments-hepatitis-c| url-status = dead| archive-url = https://web.archive.org/web/20141020015735/http://www.ctaf.org/reports/treatments-hepatitis-c| archive-date = 2014-10-20}}</ref><ref>{{cite news |url=https://www.nytimes.com/aponline/2014/03/11/business/ap-us-hepatitis-c-drug-cost.html |title=Medical Groups Question Price of New Hep C Drug|date=11 March 2014|agency=[[Associated Press]] |work=[[The New York Times]]}}</ref>

Because of sofosbuvir's 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.<ref name="WaPo_2017_Johnson">{{cite news |url=https://www.washingtonpost.com/business/economy/louisiana-considers-radical-step-to-counter-high-drug-prices-federal-intervention/2017/07/03/456b99f6-4a59-11e7-a186-60c031eab644_story.html?tid=sm_tw |title=Louisiana considers radical step to counter high drug prices: Federal intervention |first=Carolyn Y.vauthors |last= Johnson | name-list-style = vancCY |date=July 3, 2017 |access-date=July 4, 2017 |location=Baton Rouge, Louisiana |url-status=live |archive-url=https://web.archive.org/web/20170923235702/https://www.washingtonpost.com/business/economy/louisiana-considers-radical-step-to-counter-high-drug-prices-federal-intervention/2017/07/03/456b99f6-4a59-11e7-a186-60c031eab644_story.html?tid=sm_tw |archive-date=September 23, 2017 }}</ref> This puts "patients at increased risk of medical complications" and contributes to the "transmission of the hepatitis C virus".<ref name="Kapczynski_2016_patent">{{cite journal | vauthors = Kapczynski A, Kesselheim AS | title = 'Government Patent Use': A Legal Approach To Reducing Drug Spending | journal = Health Affairs | volume = 35 | issue = 5 | pages = 791–7791–797 | date = May 2016 | pmid = 27140984 | doi = 10.1377/hlthaff.2015.1120 | url = https://law.yale.edu/system/files/documents/faculty/papers/kapcyznski_govpatentuse.pdf | access-date = June 4, 2017 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20170901111149/https://law.yale.edu/system/files/documents/faculty/papers/kapcyznski_govpatentuse.pdf | url-status = live | archive-date = September 1, 2017 | doi-access = free }}</ref> In an article published in May 2016 in ''Health Affairs'', the authors proposed the invocation of the federal "[[Government patent use (United States)|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."<ref name="Kapczynski_2016_patent"/> By July 2017, Louisiana's health secretary Rebekah Gee, who described Louisiana as America's "public-health-crisis cradle", was investigating the use of the "government patent use" as a strategy.<ref name="WaPo_2017_Johnson"/>

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.<ref name="view.asiae.co.kr">{{cite web|url=http://view.asiae.co.kr/news/view.htm?idxno=2016042011590218400|title=C형간염 치료제 건강보험 적용|date=20 April 2016|access-date=2 August 2016|url-status=live|archive-url=https://web.archive.org/web/20160530185816/http://view.asiae.co.kr/news/view.htm?idxno=2016042011590218400|archive-date=30 May 2016 }}</ref><ref name="edaily.co.kr">{{cite web|url=http://www.edaily.co.kr/news/NewsRead.edy?SCD=JG11&newsid=02391126612618088&DCD=A00701&OutLnkChk=Y|title=C형 간염 치료제 신약, 내달 1일부터 건강보험 적용 |first1 trans-title =Ⓒ 종합New 경제정보hepatitis 미디어C treatment to be covered by health insurance from the 1st of next month 이데일리-상업적|last1 language =무단전재|first2=재배포|last2=금지 Korean |date=20 April 2016|access-date=2 August 2016|url-status=live|archive-url=https://web.archive.org/web/20160531042623/http://www.edaily.co.kr/news/NewsRead.edy?SCD=JG11&newsid=02391126612618088&DCD=A00701&OutLnkChk=Y|archive-date=31 May 2016 }}</ref><ref>{{cite web | url=https://www.medigatenews.com/news/3352513398 | title=Medi:gate News 6월 1일부터 하보니·소발디 가격 절반된다…하보니 급여도 확대 | trans-title = From the 1st of the month, the price of Harboni and Sovaldi will be halved… Harboni salary increase | language = Korean }}</ref>

In Switzerland, the price is fixed by the government every three years. The price in 2016 was CHF 16,102.50 (about 1:1 to the US dollar) for 24 pills of 400&nbsp;mg.<ref name="Deindoktor_2016">{{cite web|url=https://www.deindoktor.ch/en/online-medication/sovaldi-400-mg_7680632180016.html|title=Sovaldi / Sofosbuvir medication in Switzerland|url-status=live|archive-url=https://web.archive.org/web/20161004000943/https://www.deindoktor.ch/en/online-medication/sovaldi-400-mg_7680632180016.html|archive-date=2016-10-04 }}</ref>

As of 2015, sofosbuvir is included on the list of essential medications in Croatia and its cost is fully covered by the [[Croatian Health Insurance Fund]]. As a result of negotiations with the manufacturer, only therapies with successful outcome would be paid by the Fund with the rest being covered by the manufacturer.<ref name=PoslovniDnevnik>[{{cite web|url=http://www.poslovni.hr/hrvatska/tri-skupa-lijeka-za-hepatitis-c-od-danas-na-besplatnoj-listi-hzzo-a-299564 |title=Tri skupa lijeka za hepatitis C od danas na besplatnoj listi HZZO-a]}}</ref>

In July 2014, Gilead Sciences filed a patent for sofosbuvir in India. If the office of the controller general of patents had granted it, Gilead would have obtained exclusive rights to produce and sell sofosbuvir in the country. However, in January 2015, the [[Indian Patent Office]] rejected Gilead's application. Gilead's lawyers moved the [[Delhi High Court]] against this decision. That decision was overturned on appeal in February 2015.<ref>{{cite web|url=http://www.raps.org/Regulatory-Focus/News/2015/02/04/21240/India-Gilead-Patent/|title=Follow the Rules, Indian Court Tells Patent Office in Sovaldi Case|last vauthors = Mezher|first=Michael M |date=February 4, 2015|publisher=Regulatory Affairs Professionals Society|archive-url=https://web.archive.org/web/20160501185954/http://www.raps.org/Regulatory-Focus/News/2015/02/04/21240/India-Gilead-Patent/|archive-date=2016-05-01|url-status=live}}</ref><ref>{{cite web|url=http://www.thehindubusinessline.com/companies/more-patentopposition-on-gileads-hepatitis-c-drug-sofosbuvir/article6847904.ece|title=More patent-opposition on Gilead's hepatitis C drug, sofosbuvir|last vauthors = Datta|first=Jyothi J |date=2 February 2015|work=Hindu Business Line|archive-url=https://web.archive.org/web/20170923235702/http://www.thehindubusinessline.com/companies/more-patentopposition-on-gileads-hepatitis-c-drug-sofosbuvir/article6847904.ece|archive-date=23 September 2017|url-status=live|name-list-style=vanc}}</ref> In the meantime, it{{clarify|date=July 2021}} granted Indian companies voluntary licenses (VLs), which allowed them to make and sell in a selected few countries at a discounted price. This agreement also granted 7% of the royalties to Gilead. However, the list of countries open to Indian firms under this agreement excluded 73 million people with hepatitis C.<ref>{{Citecite web|url=https://caravanmagazine.in/reportage/drug-deals|title=How big pharma and the Indian government are letting millions of patients down |last vauthors = Krishnan|first=co-authored by MandakiniV, Gahlot,Vidya M |website=The Caravan|language=en|access-date=2019-07-25}}</ref>

In Egypt, which had the world's highest incidence of hepatitis C, Gilead offered sofosbuvir at the discounted price of $900 to the Egyptian government. The government in turn made it free to patients. Later, Gilead licensed a generic version to be available in Egypt.<ref>{{Citecite news|url=https://www.nytimes.com/2015/12/16/health/hepatitis-c-treatment-egypt.html|title=Curing Hepatitis C, in an Experiment the Size of Egypt|date=Dec 15, 2015|work=New York Times}}</ref>

The price has generated considerable controversy.<ref name="Stanton">{{cite web |last=Stanton |firstvauthors =Tracy | name-list-style =Stanton vancT |title=Activists pounce on $1,000-a-day price for Gilead's hep C wonder drug, Sovaldi |url=http://www.fiercepharma.com/story/activists-pounce-1000-day-price-gileads-hep-c-wonder-drug-sovaldi/2013-12-09 |work=FiercePharma |access-date=22 February 2014 |url-status=live |archive-url=https://web.archive.org/web/20140218200421/http://www.fiercepharma.com/story/activists-pounce-1000-day-price-gileads-hep-c-wonder-drug-sovaldi/2013-12-09|archive-date=18 February 2014 }}</ref><ref name="Waldman">{{cite web |last=Waldman |firstvauthors =Ron | name-list-style =Waldman vancR |title=Gilead's HCV drug sofosbuvir approved by the FDA but accessible for how many?|url=http://doctorsoftheworld.org/wp-content/uploads/2013/07/Gileads-HCV-drug-sofosbuvir-approved-but-accessible-for-how-many-09DEC2013.pdf|publisher=Doctors of the World|access-date=22 February 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140226224657/http://doctorsoftheworld.org/wp-content/uploads/2013/07/Gileads-HCV-drug-sofosbuvir-approved-but-accessible-for-how-many-09DEC2013.pdf|archive-date=26 February 2014 }}</ref> In 2017, the range of costs per treatment varied from about $84,000<ref name=Hill2016>{{cite journal | vauthors = Hill A, Simmons B, Gotham D, Fortunak J | title = Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C | journal = Journal of Virus Eradication | volume = 2 | issue = 1 | pages = 28–31 | date = January 2016 | pmid = 27482432 | pmc = 4946692 | doi = 10.1016/S2055-6640(20)30691-9 | pmid = 27482432 | pmc = 4946692 }}</ref> to about $50.<ref name=merlot/>

In February 2015, it was reported<ref>{{cite web|title=Doctors of the World—Médecins Du Monde opposes sofosbuvir patent in Europe|url=http://www.medecinsdumonde.org/gb/Doctors-of-the-World-Medecins-du-Monde-is-filing-a-patent-challenge-to-Gilead-s-patent-on-sofosbuvir-at-the-European-Patent-Office|publisher=Médecins du Monde|access-date=12 February 2015|url-status=live|archive-url=https://web.archive.org/web/20150212143338/http://www.medecinsdumonde.org/gb/Doctors-of-the-World-Medecins-du-Monde-is-filing-a-patent-challenge-to-Gilead-s-patent-on-sofosbuvir-at-the-European-Patent-Office|archive-date=12 February 2015 }}</ref> that [[Doctors of the World]] had submitted an objection to Gilead's patent<ref>{{cite web|title=European Patent EP2203462, granted 21 May 2014|url=https://register.epo.org/espacenet/regviewer?AP=08732818&CY=EP&LG=en&DB=REG|website=European Patent Register|publisher=European Patent Office|access-date=12 February 2015}}</ref> at the [[European Patent Office]], claiming that the structure of sofosbuvir is based on already known molecules.<ref name=spiegel2015>{{cite magazine |url=http://www.spiegel.de/wissenschaft/medizin/sovaldi-aerzte-der-welt-erhebt-einspruch-gegen-patent-a-1017728.html | first = Nicola | lastvauthors = Kuhrt |N name-list-style = vanc |title=Hepatitis-Pille Sovaldi: "Ärzte der Welt" geht gegen Patent vor | trans-title = Hepatitis pill Sovaldi: "Doctors of the World" takes action against the patent |magazine=[[Der Spiegel]] |language=de |date=February 10, 2015 |access-date=February 10, 2015 |url-status=live |archive-url=https://web.archive.org/web/20150210201434/http://www.spiegel.de/wissenschaft/medizin/sovaldi-aerzte-der-welt-erhebt-einspruch-gegen-patent-a-1017728.html |archive-date=February 10, 2015 }}</ref> In particular, Doctors of the World argued that the [[Protide]] technology powering sofosbuvir was previously invented by the [[Chris McGuigan]] team at [[Cardiff University]] in the UK, and that the Gilead drug is not therefore inventive.<ref>{{cite news|title=Conflit autour d'un traitement contre l'hépatite C| newspaper=Le Monde.fr | url=http://www.lemonde.fr/planete/article/2015/02/10/conflit-autour-d-un-traitement-contre-l-hepatite-c_4573300_3244.html |language=fr |date=February 10, 2015 |access-date=March 4, 2015}}</ref><ref>{{cite web|title=Charity challenges Gilead's European patent on hepatitis C therapy Sovaldi|url=http://www.firstwordpharma.com/node/1263122#axzz3RPviNrRF|date=February 10, 2015|access-date=March 4, 2015|url-status=live|archive-url=https://web.archive.org/web/20150402095143/http://www.firstwordpharma.com/node/1263122 |archive-date=April 2, 2015 }}</ref> The group filed challenges in other developing countries as well.<ref>{{cite news|url=https://www.nytimes.com/2015/05/20/business/high-cost-of-hepatitis-c-drug-prompts-a-call-to-void-its-patents.html|title=High Cost of Sovaldi Hepatitis C Drug Prompts a Call to Void Its Patents | work = The New York Times |date=20 May 2015 |url-status=live|archive-url=https://web.archive.org/web/20150523082146/http://www.nytimes.com/2015/05/20/business/high-cost-of-hepatitis-c-drug-prompts-a-call-to-void-its-patents.html?_r=0|archive-date=2015-05-23 |last1 vauthors = Pollack |first1=AndrewA }}</ref> These challenges were unsuccessful and the court recognized the innovative step in pro-drug design and application to the specific example of sofosbuvir.{{cn|date=November 2022}}

Combinations of sofosbuvir with NS5A inhibitors, such as [[daclatasvir]], [[ledipasvir]] or [[Velpatasvir/sofosbuvir|velpatasvir]], have shown sustained virological response rates of up to 100% in people infected with HCV. Most studies indicate that the efficacy rate is between 94% and 97%; much higher than previous treatment options.<ref>{{cite journal | vauthors = Childs-Kean LM, Hand EO | title = Simeprevir and sofosbuvir for treatment of chronic hepatitis C infection | journal = Clinical Therapeutics | volume = 37 | issue = 2 | pages = 243–67243–267 | date = February 2015 | pmid = 25601269 | doi = 10.1016/j.clinthera.2014.12.012 }}</ref><ref>{{cite journal | vauthors = Smith MA, Chan J, Mohammad RA | title = Ledipasvir-sofosbuvir: interferon-/ribavirin-free regimen for chronic hepatitis C virus infection | journal = The Annals of Pharmacotherapy | volume = 49 | issue = 3 | pages = 343–50343–350 | date = March 2015 | pmid = 25515863 | doi = 10.1177/1060028014563952 | s2cid = 20944806 }}</ref><ref name=FDA2017Ep>{{Citecite journal|url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm508915.htm|title = FDA approves Epclusa for treatment of chronic Hepatitis C virus infection|last publisher = FDAU.S. Food and Drug Administration |first journal = News Release|date = June 28, 2016|url-status = live|archive-url = https://web.archive.org/web/20170603100010/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm508915.htm|archive-date = June 3, 2017}}</ref> That treatments could be conducted at very low costs was demonstrated by Hill and coworkers who presented data on 1,160 patients who used generic versions of solfosbuvir, ledipasvir, plus daclatasvir from suppliers in India, Egypt, China and other countries and reported over 90% success at costs of about $50 per therapy.<ref name=merlot>{{cite magazine |url=http://www.spiegel.de/gesundheit/diagnose/hepatitis-c-koennte-fuer-50-dollar-therapiert-werden-a-1176133.html | first = Julia | lastvauthors = Merlot | name-list-style = vancJ |title=Hepatitis C könnte für 50 Dollar geheilt werden |magazine=[[Der Spiegel]] |language=de| date=November 2, 2017 |access-date=November 2, 2017}}</ref>

Sofosbuvir has also been tested against other viruses such as the [[Zika virus]]<ref>{{cite journal |last1 vauthors = Sacramento |first1=CarolinaCQ, Q. |last2=de Melo |first2=GabrielleGR, R. |last3=de Freitas |first3=CarolineCS, S. |last4=Rocha |first4=NatashaN, |last5=Hoelz |first5=LucasLV, Villas Bôas |last6=Miranda |first6=MileneM, |last7=Fintelman-Rodrigues |first7=NataliaN, |last8=Marttorelli |first8=AndressaA, |last9=Ferreira |first9=AndréAC, C. |last10=Barbosa-Lima |first10=GiselleG, |last11=Abrantes |first11=JulianaJL, L. |last12=Vieira |first12=YasmineYR, Rangel |last13=Bastos |first13=MônicaMM, M. |last14=de Mello Volotão |first14=EduardoE, |last15=Nunes |first15=EstevãoEP, Portela |last16=Tschoeke |first16=DiogoDA, A. |last17=Leomil |first17=LucianaL, |last18=Loiola |first18=ErickEC, Correia |last19=Trindade |first19=PabloP, |last20=Rehen |first20=StevensSK, K. |last21=Bozza |first21=FernandoFA, A. |last22=Bozza |first22=PatríciaPT, T. |last23=Boechat |first23=NubiaN, |last24=Thompson |first24=FabianoFL, L. |last25=de Filippis |first25=AnaAM, M.Brüning B.K, |last26=BrüningSouza |first26=KarinTM |last27=Souza |first27display-authors =Thiago Moreno L.6 | title = The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication | journal = Scientific Reports |date=18 January 2017 |volume = 7 | issue = 1 |page pages = 40920 |doi date =10.1038/srep40920 January 2017 | pmid = 28098253 | pmc = 5241873 | doi = 10.1038/srep40920 | bibcode = 2017NatSR...740920S | doi-access = free }}</ref> and [[severe acute respiratory syndrome coronavirus 2]] (SARS-CoV-2).<ref>{{cite journal |last1 vauthors =Elfiky Mesci P, de Souza JS, Martin-Sancho L, Macia A, Saleh A, Yin X, Snethlage C, Adams JW, Avansini SH, Herai RH, Almenar-Queralt A, Pu Y, Szeto RA, Goldberg G, Bruck PT, Papes F, Chanda SK, Muotri AR |first1 display-authors =Abdo 6 | title =Sofosbuvir CanSARS-CoV-2 Inhibitinfects thehuman Newlybrain Emergedorganoids Coronaviruscausing (2019-nCoV)cell indeath Wuhan,and Chinaloss of synapses that can be rescued by treatment with Sofosbuvir |date journal =20 JanuaryPLOS 2020Biology |url volume =https://ssrn.com/abstract 20 | issue =3523869 11 |access- pages = e3001845 | date =2 FebruaryNovember 20202022 |publisher pmid =Social Science36327326 Research| Networkpmc = 9632769 |language doi =en 10.1371/journal.pbio.3001845 | doi-access = free }}</ref>

* [[Tenofovir alafenamide]]—a nucleotide [[reverse-transcriptase inhibitor]] that uses similar phosphoramidate prodrug technology<ref>{{cite web|title=Comparison of tenofovir prodrugs: TAF vs TDF|url=https://yixiblog.wordpress.com/tag/tenofovir-alafenamide-fumarate/|website=DRUG R&D INSIGHT|date=24 January 2015 |access-date=24 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151125032215/https://yixiblog.wordpress.com/tag/tenofovir-alafenamide-fumarate/|archive-date=25 November 2015 }}</ref><ref name="pmid20801890"/>