Medications to Treat Hepatitis C – A Timeline
The Hepatitis C virus was discovered in 1989. Since then significant research, testing and public health awareness has led to a decrease in HCV transmission as well as treatments leading to a cure. Since 1989 interferon has been the main component of treatment options, however new medications have been made available in recent years showing higher sustained virologic response (SVR) rates, especially for genotype 1, the most predominant genotype in the world.
Below is a timeline summarizing the history of HCV and treatment options in the United States. For treatment protocols, please see Hepatitis C Treatments By Genotype.
Generic versions of sofosbuvir/velpatasvir (trade name Epclusa) and (ledipasvir/sofosbuvir) (trade name Harvoni) announced.
In June, Rebetol was discontinued due to business reasons unrelated to any safety, efficacy or quality issues.
Also in June, all versions of Daklinza were discontinued.
Olysio was discontinued May 25, 2019 due to obsolescence.
December 31, 2018 Viekira XR and Technivie were discontinued for business reasons unrelated to safety or effectiveness. Viekira Pak is still available.
Mavyret (glecaprevir and pibrentasvir), was approved in August as the first 8 week treatment for all HCV genotypes without cirrhosis who have not been previously treated. Results of the trials demonstrated that 92-100 percent of patients who received Mavyret for eight, 12 or 16 weeks duration had no virus detected in the blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured.
July 18, 2017, FDA approves Gilead’s Vosevi (sofosbuvir, velpatasvir and voxilaprevir) as the first once-daily, single-table regimen approved for patients with genotypes 1-6 who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A. Trials demonstrated that 96-97 percent of patients who received Vosevi had no virus detected in the blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured.
On January 28th Zepatier, a combination of elbasvir and grazoprevir, with or without ribavirin earned FDA approval. Trials demonstrated sustained virologic response (SVR) rates of up to 97 percent in genotype 1 patients and up to 100 percent in patients with genotype 4.
Epclusa (sofosbuvir/velpatasvir) was approved on June 28th as the first all-oral, single tablet regimen for the treatment of adults with genotype 1-6 chronic hepatitis C virus infection. Epclusa is also the first single tablet regimen approved for the treatment of patients with HCV genotype 2 and 3, without the need for ribavirin. After 12 weeks, 98 percent of patients taking Epclusa achieved SVR and 94 percent of patients with decompensated cirrhosis taking Epclusa with ribavirin achieved SVR.
Later in 2016, the makers of Viekira Pak (2014) introduced Viekira XR which included the same medications as Viekira Pak but was instead a single fixed-dose combination tablet instead of a 2 tablet package.
As of January, Merck discontinued selling Victrelis, which had been introduced to the market in 2011.
Daklinza (daclatasvir), was approved in July for use with sofosbuvir as the first 12-week, all-oral treatment option for patients with chronic hepatitis C virus genotype 3. SVR rates are reduced in HCV genotype 3 infected patients with cirrhosis.
Also approved in July, Technivie (ombitasvir, paritaprevir and ritonavir) is used in combination with ribavirin for the treatment of HCV genotype 4 infections in patients that do not have scarring and poor liver function (cirrhosis). Technivie is the first drug approved to treat genotype 4 HCV infection without interferon.
In August, Vertex discontinued selling Incivek, which had been introduced to the market just a few years prior, in 2011.
The FIRST once-daily pill that doesn’t require interferon or ribavirin, Harvoni (ledipasvir/sofosbuvir) tablets are approved by the FDA in October. This medication is indicated for the treatment of hepatitis c, genotype 1 infections.
Two months later, the FDA approves Viekira Pak (ombitasvir/paritaprevir/ritonavir and dasabuvir) oral combination therapy for the treatment of patients with genotype 1 HCV infection including those with compensated cirrhosis. Limitations of use include those with decompensated liver disease.
In November, the FDA approves Olysio (simeprevir) capsules to be used in combination with peginterferon alfa and ribavirin or in combination with sofosbuvir. Its efficacy is established in patients with hepatitis c genotype 1. In addition to other limitations, simeprevir isn’t recommended for those that have failed previous treatment regimens that included simeprevir or other HCV protease inhibitors.
The following month, the FDA approves Sovaldi (sofosbuvir) tablets to be used in combination with ribavirin or with pegylated interferon and ribavirin. Its efficacy is established in patients with hepatitis c genotypes 1, 2, 3 or 4, including those with hepatocellular carcinoma awaying liver transplant and those with hepatitis c/HIV co-infection. Duration of treatment is usually 12-24 weeks.
On May 13th, the FDA approves Victrelis (boceprevir) for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy, including prior null responders, partial responders, and relapsers.
Ten days later, on May 23rd, Incivek (telaprevir) is approved by the FDA for use in combination with peginterferon alfa and ribavirin for the treatment of genotype 1 HCV infection in adults with compensated liver disease, including cirrhosis, who are treatment-naïve or who have been previously treated with interferon-based treatment, including prior null responders, partial responders, and relapsers.
Pegasys (peginterferon alfa-2a) produced by Genentech, Inc. is approved by the FDA in October for the treatment of chronic HCV as part of a combination therapy.
In December, Genentech, Inc. gets FDA approval for its version of ribavirin, Copegasus. Copegasus is indicated for the treatment of chronic hepatitis C virus infection in combination with Pegasys in patients 5 years of age and older with compensated liver disease that were not previously treated with interferon alpha as well as in adults coinfected with HIV.
Merck’s Pegintron (peginterferon alfa-2b) injections are approved by the FDA and is indicated for the treatment of chronic HCV patients with compensated liver disease. For certain patients peginterferon alfa-2b may be administered with ribavirin.
FDA approves Merck’s Rebetol (ribavirin) to be used in combination with interferon alfa-2b (both pegylated and non-pegylated) injections for the treatment of chronic hepatitis c in patients 3 years of age and older with compensated liver disease. Additionally, Schering-Plough announces that the FDA has approved the combination use of Rebetol and Intron to be marketed as Rebetron for the treatment of chronic hepatitis C in patients with compensated liver disease who have relapsed following interferon therapy.
FDA approves Infergen (interferon alfacon-1) injection sometimes taken in combination with ribavirin for the treatment of chronic HCV in patients 18 years of age and older with compensated liver disease.
The United States blood supply is tested for HCV. Although routine testing for Hepatitis C began in 1990, more sensitive testing of the U.S. Blood supply virtually eliminated the HCV from all its blood banks.
The first Hepatitis C treatment is approved by the FDA. The Food & Drug Administration (FDA) approves the first treatment for Hepatitis C – Schering-Plough’s Intron A. Unfortunately, the initial treatment resulted in very few people actually clearing the virus.
Hepatitis C Virus is identified!
Non-A, non-B hepatitis was recognized in the mid-1970’s. While non-A, non-B hepatitis was originally thought to be insignificant, it was later realized that it was a disease that often advanced silently to cirrhosis and even cancer. Efforts were directed at identifying its cause and seeking out drug treatments that might impede its advance.
Older HCV Treatment Information and Clinical Studies
25 Years of Interferon-Based Treatment of Chronic Hepatitis C: An Epoch Coming to an End. http://www.nature.com/nri/journal/v13/n7/full/nri3463.html, Nature Reviews Immunology. Retrieved May 5, 2018.
A Brief History of the Treatment of Viral Hepatitis C. http://onlinelibrary.wiley.com/doi/10.1002/cld.1/full, Wiley Online Library. Retrieved May 5, 2017.
Advances in Medications to Treat Hepatitis C. http://hepc.liverfoundation.org/treatment/the-basics-about-hepatitis-c-treatment/advances-in-medications/, American Liver Foundation. April 2015. Retrieved May 5, 2018.
ALLY-1 Trial Results Show Investigational Daclatasvir-Based Regimen Cures 94% of Post-Liver Transplant Patients with Hepatitis C and Up to 94% of Hepatitis C Patients with Cirrhosis (Child-Pugh Class A or B). target="_blank">http://news.bms.com/press-release/ally-1-trial-results-show-investigational-daclatasvir-based-regimen-cures-94-post-live, Bristol-Myers Squibb. Retrieved May 5, 2018.
Authorized Generics of Epclusa, Harvoni Will Soon Be Available for HCV Treatment. https://www.empr.com/home/news/generics-news/authorized-generics-of-epclusa-harvoni-will-soon-be-available-for-hcv-treatment/, MPR Publications. Retrieved September 30, 2018.
Daklinza (daclatasvir) - Product Discontinuation. https://professionals.optumrx.com/content/dam/optum3/professional-optumrx/news/rxnews/drug-recalls-shortages/drugwithdrawal_daklinza_2019-0107.pdf, OptumRx. Retrieved January 16, 2019.
Drugs@FDA. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm, U.S. Food and Drug Administration. Retrieved May 5, 2018.
Hepatitis C: 25 Years of Discovery. http://www.cdc.gov/knowmorehepatitis/Timeline.htm, Centers for Disease Control and Prevention. Retrieved May 5, 2018.
Hepatitis C Drug Incivek to Be Discontinued. https://www.empr.com/home/news/hepatitis-c-drug-incivek-to-be-discontinued/, MPR Publications. Retrieved September 9, 2014.
Highlights of Prescribing Information - COPEGASUS. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021511s023lbl.pdf, Genentech USA, Inc. Retrieved May 5, 2018.
Highlights of Prescribing Information - DAKLINZA. http://packageinserts.bms.com/pi/pi_daklinza.pdf, Bristol-Myers Squibb Company. Retrieved July 27, 2018.
Highlights of Prescribing Information - HARVONI. http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf, Gilead Sciences, Inc. Retrieved May 5, 2018.
Highlights of Prescribing Information - INCIVEK. http://pi.vrtx.com/files/uspi_telaprevir.pdf, Vertex Pharmaceuticals, Inc. Retrieved May 5, 2018.
Highlights of Prescribing Information - INFERGEN. http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Infergen_PI_2010.pdf, Three Rivers Pharmaceuticals, LLC. Retrieved May 5, 2018.
Highlights of Prescribing Information - OLYSIO. http://www.olysio.com/shared/product/olysio/prescribing-information.pdf, Janssen Products. Retrieved May 5, 2018.
Highlights of Prescribing Information - PEGASYS. http://www.gene.com/download/pdf/pegasys_prescribing.pdf, Genentech USA, Inc. Retrieved May 5, 2018.
Highlights of Prescribing Information - PEGINTRON. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/103949s5311lbl.pdf, U.S. Food & Drug Administration. Retrieved May 5, 2018
Highlights of Prescribing Information - REBETOL. https://www.merck.com/product/usa/pi_circulars/r/rebetol/rebetol_pi.pdf, Merck Sharpe & Dohme Corp. Inc. Retrieved May 5, 2018.
Highlights of Prescribing Information - SOVALDI. http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf, Gilead Sciences, Inc. Retrieved May 5, 2018.
Highlights of Prescribing Information - TECHNIVIE. http://rxabbvie.com/pdf/technivie_pi.pdf, AbbVie, Inc. Retrieved July 28, 2018.
Highlights of Prescribing Information - VICTRELIS. https://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf, Merck Sharpe & Dohme Corp. Retrieved May 5, 2015.
Highlights of Prescribing Information - VIEKIRA PAK. http://www.rxabbvie.com/pdf/viekirapak_pi.pdf., AbbVie, Inc. Retrieved May 5, 2018.
Merck Drops Price for Hepatitis C Drug by 60%: GoodRx Monthly Report. https://www.goodrx.com/blog/merck-drops-price-for-hepatitis-c-drug-monthly-report-october-2018/, GoodRx, Inc. Retrieved November 12, 2018.
Phase 3 UNITY Trials Demonstrate High Cure Rates for Investigational, All-Oral Daclatasvir TRIO Fixed-Dose Combination in Gentype1 Hepatitis C Patients, Including Those with Cirrhosis. http://news.bms.com/press-release/rd-news/phase-3-unity-trials-demonstrate-high-cure-rates-investigational-all-oral-dacl., Bristol-Myers Squibb. Retrieved May 6, 2018.
Product Information - Rebetron Combination Therapy. http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/20903s23lbl.pdf, Schering Corporation. Retrieved May 5, 2018.
Rebetol - Product Discontinuation. https://professionals.optumrx.com/content/dam/optum3/professional-optumrx/news/rxnews/drug-recalls-shortages/drugwithdrawal_rebetol_2019-0417.pdf, OptumRx. Retrieved May 15, 2019.
Subject: Hepatitis C Drug Will Be Discontinued. https://coventrywcs.com/content/dam/pdf_assets/first_script_bulletins/2018/CLINICAL_BULLETIN-Hep-C_Drug_Discontinued_20180502.pdf, Coventry. Retrieved May 15, 2018.
Technivie (ombitasvir/paritaprevir/ritonavir) and Viekira XR(dasabuvir/ombitasvir/paritaprevir/ritonavir) – Product Discontinuations. https://professionals.optumrx.com/content/dam/optum3/professional-optumrx/news/rxnews/drug-recalls-shortages/drugwithdrawal_technivie_viekiraxr_2018-0424.pdf, OptumRx. Retrieved June 10, 2018.
Two HCV Treatments to Be Discontinued. https://hepatitisc.net/news/two-treatments-discontinued/, HepatitisC.net. Retrieved June 20, 2018.