Sofosbuvir/velpatasvir, sold under the brand name Epclusa among others, is a

fixed-dose combination A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC pr ...

medication for the treatment of

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

in adults. It combines

sofosbuvir Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken Oral administration, by mouth. Common side effects include fatigue, headache, nausea, and trouble sleeping. Side effects are gen ...

and

velpatasvir Velpatasvir is an NS5A inhibitor (by Gilead) which is used together with sofosbuvir in the treatment of hepatitis C infection of all six major genotypes. Side effects Side effects in studies occurred with similar frequencies as in people treat ...

. It is more than 90% effective for hepatitis C

genotypes The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

one through six. It also works for hepatitis C in those who also have

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...

HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...

. It is taken by mouth. In March 2020, sofosbuvir/velpatasvir was approved for use in the United States to treat hepatitis C virus (HCV) in children ages six years and older or weighing at least 37 pounds (17 kilograms) with any of the six HCV genotypes—or strains—without cirrhosis (liver disease) or with mild cirrhosis. Sofosbuvir/velpatasvir in combination with ribavirin is indicated for the treatment of children six years and older or weighing at least 37 pounds with severe cirrhosis. The combination is generally well tolerated. Common side effects include headaches,

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, trouble sleeping, and

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

. The combination has not been studied in pregnant women or during

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

. Greater care is required in those who are also infected with

hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

. Sofosbuvir works by blocking the

NS5B Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA-dependent RNA polymerase, having the key function of replicating HCV's viral RNA by using the viral positive RNA strand as a template to catalyze ...

protein and velpatasvir works by blocking the

NS5A Nonstructural protein 5A (NS5A) is a zinc-binding and proline-rich hydrophilic phosphoprotein that plays a key role in Hepatitis C virus RNA replication. It appears to be a dimeric form without ''trans''-membrane helices. Structure NS5A is deriv ...

protein. Sofosbuvir/velpatasvir was approved for medical use in the United States and in Europe in 2016. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

Medical uses

A single tablet regimen is used for adults with genotype 1–6 chronic hepatitis C virus (HCV) infection.

Contraindications

Combining sofosbuvir/velpatasvir with strong inducers of the liver enzymes

CYP2B6 Cytochrome P450 2B6 is an enzyme that in humans is encoded by the ''CYP2B6'' gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances. Funct ...

CYP2C8 Cytochrome P4502C8 (abbreviated CYP2C8), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-cha ...

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

, or with

P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...

, is contraindicated because such substances may reduce the effectiveness of the drug.

Side effects

Common side effects (in more than 10% of people) are headache, fatigue and nausea. In studies, severe side effects were experienced in 3% of patients, and 0.2% terminated the therapy because of adverse events. These effects occurred with similar frequencies in people treated with

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

Interactions

Pharmacokinetics

History

Beacon Pharmaceuticals in Bangladesh introduced a generic version product under the trade name of Sofosvel. Beacon received approval from the Directorate of Drug Administration,

Ministry of Health and Family Welfare The Ministry of Health and Family Welfare is an Indian government ministry charged with health policy in India. It is also responsible for all government programs relating to family planning in India. The Minister of Health and Family Welfare ...

, People's Republic of Bangladesh.US' Gilead faces competition from Bangladesh's Beacon pharma
,

The Economic Times ''The Economic Times'' is an Indian English-language business-focused daily newspaper. It is owned by The Times Group. ''The Economic Times'' began publication in 1961. As of 2012, it is the world's second-most widely read English-language bus ...

Sofosbuvir/velpatasvir was developed by the pharmaceutical company

Gilead Sciences Gilead Sciences, Inc. () is an American biopharmaceutical company headquartered in Foster City, California, that focuses on researching and developing antiviral drugs used in the treatment of HIV/AIDS, hepatitis B, hepatitis C, influenza, and CO ...

and approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) in June 2016. In the European Union it was approved in July 2016, for the treatment of chronic hepatitis C virus infection in adults. The safety and efficacy of sofosbuvir/velpatasvir for a 12-week treatment was evaluated in three Phase III clinical trials of 1,558 subjects without cirrhosis or with compensated cirrhosis (mild cirrhosis). Results demonstrated that 95–99 percent of subjects who received sofosbuvir/velpatasvir had no virus detected in the blood 12 weeks after finishing treatment, suggesting the subjects' infections had been cured. The safety and efficacy of sofosbuvir/velpatasvir was also evaluated in a clinical trial of 267 subjects with decompensated cirrhosis (moderate to severe cirrhosis), of whom 87 subjects received sofosbuvir/velpatasvir in combination with ribavirin for 12 weeks, and 94 percent of these subjects had no virus detected in the blood 12 weeks after finishing treatment. The pharmacokinetics (how the body absorbs, distributes and rids itself of a drug), safety and efficacy of sofosbuvir/velpatasvir, taken orally for 12 weeks, for the treatment of HCV genotypes 1, 2, 3, 4 or 6 infection was established in an open-label, multicenter clinical trial that included a total of 173 treatment-naïve and treatment-experienced pediatric subjects ages six years and older without cirrhosis or with mild cirrhosis. No meaningful differences in pharmacokinetics were seen in pediatric subjects compared to adults. The safety and efficacy results were comparable to those observed in adults. In 102 subjects ages 12 through 17, 93% of subjects with genotype 1 and 100% of subjects with genotypes 2, 3, 4 and 6 had no detectable virus in the blood 12 weeks after finishing treatment, suggesting the subjects' infection was cured. Among the 71 subjects ages 6 to 11 years with HCV genotypes 1, 2, 3 or 4, 93% with genotype 1, 91% with genotype 3 and 100% with genotypes 2 and genotype 4 had no virus detected in the blood 12 weeks after finishing treatment. The safety and efficacy of sofosbuvir/velpatasvir for treatment of HCV genotype 5 in pediatric subjects six years and older or weighing at least 37 pounds without cirrhosis or with mild cirrhosis are supported by sofosbuvir and velpatasvir exposures in adults and pediatric subjects with HCV genotype 1, 2, 3, 4 or 6 infection. Similar data were used to support dosing recommendations for pediatric subjects with HCV genotype 1, 2, 3, 4, 5 or 6 infection who have severe cirrhosis. The safety and effectiveness of sofosbuvir/velpatasvir have not been established in people less than six years of age. The U.S.

(FDA) granted the application of sofosbuvir/velpatasvir

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

and granted the approval of Epclusa to Gilead Sciences, Inc.

References

External links

* {{DEFAULTSORT:Sofosbuvir Velpatasvir Combination drugs Gilead Sciences NS5A inhibitors NS5B (polymerase) inhibitors World Health Organization essential medicines Wikipedia medicine articles ready to translate Breakthrough therapy