MedPath

Sofosbuvir

Generic Name
Sofosbuvir
Brand Names
Epclusa, Harvoni, Sovaldi, Vosevi
Drug Type
Small Molecule
Chemical Formula
C22H29FN3O9P
CAS Number
1190307-88-0
Unique Ingredient Identifier
WJ6CA3ZU8B

Overview

Sofosbuvir (tradename Sovaldi) is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients . Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as sofosbuvir. As a prodrug nucleotide analog, Sofosbuvir is metabolized into its active form as the antiviral agent 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-triphosphate (also known as GS-461203), which acts as a defective substrate for NS5B (non-structural protein 5B) . NS5B, an RNA-dependent RNA polymerase, is essential for the transcription of Hepatitis C viral RNA and for its high replicative rate and genetic diversity . Sofosbuvir and other direct acting antivirals are therefore very potent options for the treatment of Hepatitis C, as they exhibit a high barrier to the development of resistance . This is an important advantage relative to HCV drugs that target other viral enzymes such as the protease, for which rapid development of resistance has proven to be an important cause of therapeutic failure. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Sofosbuvir as first line therapy in combination with other antivirals for all six genotypes of Hepatitis C . Depending on the genotype, sofosbuvir is often used in combination with other antivirals such as Ledipasvir, Velpatasvir, Daclatasvir, Simeprevir, Elbasvir, Grazoprevir, Ribavirin, Peginterferon alfa-2a, or Peginterferon alfa-2b with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality . Treatment with direct acting antivirals such as sofosbuvir is associated with very minimal side effects, with the most common being headache and fatigue . Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon- and ribavirin-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects . Since 2014, sofosbuvir has been available as a fixed dose combination product with Ledipasvir (tradename Harvoni) used for the treatment of chronic Hepatitis C. Approved in October 2014 by the FDA, Harvoni is indicated for the treatment of HCV genotypes 1, 4, 5, and 6 with or without Ribavirin depending on the level of liver damage or cirrhosis . When combined together, ledipasvir and sofosbuvir as the combination product Harvoni has been shown to achieve a SVR between 93 and 99% after 12 weeks of treatment . Its use has also proven successful in the treatment of HCV in patients co-infected with HIV . Sofosbuvir is also available as a fixed dose combination product with Velpatasvir as the commercially available product Epclusa. First approved in June 2016, Epclusa is the first combination HCV product indicated for the treatment of all genotypes of Hepatitis C with or without cirrhosis. Epclusa is also currently the most potent HCV antiviral medication on the market with a sustained virologic response (SVR) after 12 weeks of therapy of 93-99% depending on genotype and level of cirrhosis . Both Canadian and American guidelines list Epclusa as a first line recommendation for all genotypes of HCV . Notably, sofosbuvir has come under intense scrutiny since its release to market in 2013. With the price per pill set at $1000, a 12-week treatment can cost upwards of $84,000 per patient .

Indication

Sofosbuvir is used in combination therapy with other antiviral medications to treat chronic hepatitis C virus (HCV) infected patients with HCV genoptypes 1-6, and to treat HCV and HIV co-infected patients. Depending on the level of cirrhosis or decompensation, combination therapy can also include either ribavirin alone or ribavirin and peg-interferon alfa. When used in combination with Ledipasvir, sofosbuvir has the following indications: treatment of genotypes 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis; in combination with Ribavirin for genotype 1 infection with decompensated cirrhosis; or in combination with Ribavirin for the treatment of genotype 1 or 4 infection who are liver transplant recipients without cirrhosis or with compensated cirrhosis. When used in combination with Velpatasvir as the combination product Epclusa, sofosbuvir is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) genotypes 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis, or in combination with Ribavirin if associated with decompensated cirrhosis. Resistance: Reduced susceptibility to sofosbuvir has been associated with the NS5B substitution mutation S282T .

Associated Conditions

  • Chronic Hepatitis C - Genotype 3
  • Chronic Hepatitis C Genotype 1
  • Chronic Hepatitis C Virus (HCV) Infection
  • Chronic hepatitis C genotype 1a
  • Chronic hepatitis C genotype 2
  • Chronic hepatitis C genotype 5
  • Genotype 4 Chronic Hepatitis C
  • Genotype 6 chronic hepatitis C infection

Research Report

Published: Jul 22, 2025

Sofosbuvir (DB08934): A Comprehensive Monograph

I. Introduction and Drug Identification

A. Executive Summary

Sofosbuvir represents a paradigm shift in the treatment of chronic Hepatitis C Virus (HCV) infection, a global public health threat responsible for significant liver-related morbidity and mortality. As a first-in-class, direct-acting antiviral (DAA), Sofosbuvir is a highly potent, pan-genotypic nucleotide analog inhibitor of the HCV non-structural protein 5B (NS5B) RNA-dependent RNA polymerase.[1] Its development heralded the era of interferon-free, all-oral therapeutic regimens, fundamentally transforming the management of HCV from a chronic, difficult-to-treat condition to a curable disease.

The clinical success of Sofosbuvir is rooted in its sophisticated prodrug design, which facilitates efficient oral absorption and targeted delivery to hepatocytes, the site of viral replication.[2] Once intracellularly activated to its triphosphate form, it acts as a chain terminator, halting viral RNA synthesis with a high barrier to the development of resistance.[1] This mechanism underpins the remarkable efficacy of Sofosbuvir-based combination therapies, which consistently achieve sustained virologic response (SVR) rates exceeding 90-95%, effectively curing the infection.[1] These regimens offer a dramatically improved safety profile and shorter treatment durations compared to older interferon-based therapies.[1]

Continue reading the full research report

Clinical Trials

Title
Posted
Study ID
Phase
Status
Sponsor
2025/05/01
Phase 4
Recruiting
2023/12/22
N/A
Recruiting
The Third Affiliated Hospital of Guangzhou Medical University
2023/05/11
Phase 3
Recruiting
2023/02/08
Phase 4
Terminated
2022/11/15
Phase 2
Completed
2022/08/17
N/A
Not yet recruiting
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
2021/08/09
Phase 4
UNKNOWN
2021/05/13
Phase 2
Completed
Muhammad Radzi Abu Hassan
2021/02/26
Phase 4
Completed
2021/01/05
Phase 4
Completed

FDA Drug Approvals

Approved Product
Manufacturer
NDC Code
Route
Strength
Effective Date
Gilead Sciences, Inc.
61958-2202
ORAL
400 mg in 1 1
12/18/2020
Gilead Sciences, Inc.
61958-2204
ORAL
200 mg in 1 1
4/30/2022
Gilead Sciences, Inc.
61958-2201
ORAL
400 mg in 1 1
4/30/2022
Asegua Therapeutics LLC
72626-2701
ORAL
400 mg in 1 1
4/30/2022
Gilead Sciences, Inc.
61958-2401
ORAL
400 mg in 1 1
11/21/2019
Asegua Therapeutics LLC
72626-2601
ORAL
400 mg in 1 1
3/13/2020
Gilead Sciences, Inc.
61958-2203
ORAL
200 mg in 1 1
4/30/2022
Gilead Sciences, Inc.
61958-2205
ORAL
150 mg in 1 1
4/30/2022
Gilead Sciences, Inc.
61958-1505
ORAL
200 mg in 1 1
3/12/2020
Gilead Sciences, Inc.
61958-1503
ORAL
200 mg in 1 1
3/12/2020

NMPA Drug Approvals

Approved Product
Company
Approval Number
Drug Type
Dosage Form
Approval Date
No NMPA approvals found for this drug.

PPB Drug Approvals

Approved Product
Registration No.
Company
Licence No.
Strength
Registration Date
VOSEVI TABLETS
N/A
N/A
N/A
6/19/2018

Health Canada Drug Approvals

Approved Product
Company
DIN
Dosage Form
Strength
Market Date
SOVALDI
gilead sciences canada inc
02418355
Tablet - Oral
400 MG
1/6/2014
EPCLUSA
gilead sciences canada inc
02456370
Tablet - Oral
400 MG
8/2/2016

CIMA AEMPS Drug Approvals

Approved Product
Company
Registration Number
Pharmaceutical Form
Prescription Type
Status
HARVONI 90 MG/400 MG COMPRIMIDOS RECUBIERTOS CON PELICULA
114958001
COMPRIMIDO RECUBIERTO CON PELÍCULA
Diagnóstico Hospitalario
Commercialized
VOSEVI 400 MG/100 MG/100 MG COMPRIMIDOS RECUBIERTOS CON PELICULA
1171223001
COMPRIMIDO RECUBIERTO CON PELÍCULA
Diagnóstico Hospitalario
Commercialized
EPCLUSA 200 MG/50 MG GRANULADO RECUBIERTO EN SOBRE
1161116004
GRANULADO RECUBIERTO
Diagnóstico Hospitalario
Commercialized
EPCLUSA 400 MG/100 MG COMPRIMIDOS RECUBIERTOS CON PELICULA
1161116001
COMPRIMIDO RECUBIERTO CON PELÍCULA
Diagnóstico Hospitalario
Commercialized
SOVALDI 400mg comprimidos recubiertos con pelicula
113894001
COMPRIMIDO RECUBIERTO CON PELÍCULA
Diagnóstico Hospitalario
Commercialized
EPCLUSA 150 MG/37,5 MG GRANULADO RECUBIERTO EN SOBRE
1161116003
GRANULADO RECUBIERTO
Diagnóstico Hospitalario
Commercialized
EPCLUSA 400 MG/100 MG COMPRIMIDOS RECUBIERTOS CON PELICULA
1161116001IP
COMPRIMIDO RECUBIERTO CON PELÍCULA
Diagnóstico Hospitalario
Commercialized

Philippines FDA Drug Approvals

Approved Product
Company
License Number
Dosage Form
Strength
Approval Date
No Philippines FDA approvals found for this drug.

Saudi SFDA Drug Approvals

Approved Product
Company
License Number
Dosage Form
Strength
Approval Date
No Saudi SFDA approvals found for this drug.

Malaysia NPRA Drug Approvals

Approved Product
Company
Registration Number
Dosage Form
Strength
Approval Date
No Malaysia NPRA approvals found for this drug.

UK EMC Drug Information

Medicine Name
MA Holder
MA Number
Pharmaceutical Form
Active Ingredient
Authorization Date
No UK EMC drug information found for this drug.

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