Oral Hepatitis C Treatments: The Evolving Landscape
What is Chronic Hepatitis C Virus (HCV)?
Roughly 30 percent of those infected with HCV will eventually develop cirrhosis. Older treatment options for HCV were plagued by lack of an all-oral regimen, unpleasant side effects with interferon agents and long treatment times often over 1 year. Newer oral treatment regimens - Sovaldi, Olysio, Harvoni, Daklinza, Zepatier, and Epclusa - aim to be more tolerable with shorter treatment times - some as short as 8 or 12 weeks.
HCV: Symptoms and Diagnosis
Longer-term (chronic) symptoms may include weight loss, poor appetite, feeling tired, and painful joints. Diagnosis involves a blood test and to determine the subtypes (genotypes) of HCV. It is important to know the genotypes to select the correct treatment. In some patients, a liver biopsy is required. In those who eventually develop cirrhosis (scarring disease of the liver), symptoms may include stomach swelling, easy bruising, difficulty breathing, jaundice, and confusion. About 5% to 20% of HCV patients will develop cirrhosis over a period of 20 to 30 years.
Hepatitis C Virus Infection: How Do You Get It?
HCV is transmitted through contact with infected blood - mainly by sharing needles or devices during drug abuse, from an accidental needle stick, renal dialysis, from mother to child during childbirth, from contaminated tattoo or body piercing equipment, and rarely from unprotected sexual intercourse or blood transfusions.
If you were born from 1945 through 1965 speak to your doctor about being tested for HCV.
The Different Genotypes for Hepatitis C Virus
Effectiveness of drugs vary based on which HCV strain a patient may be infected with - for example, Sovaldi (sofosbuvir), approved as the first all-oral regimen in 2013, can be combined with only ribavirin to treat genotypes 2 and 3; add peginterferon alfa and genotypes 1 and 4 can be treated. Harvoni (ledipasvir/sofosbuvir) was approved in 2014 as the first all-oral, ribavirin and interferon-free treatment. It can be used for Genotype 1, the most common subgroup, occurring in roughly 70% of infected patients, as well and types 4, 5 and 6. Epclusa (sofosbuvir and velpatasvir) was approved for all 6 major genotypes in June 2016.
What's Involved With An HCV Diagnosis?
Hepatitis C screening starts with a blood test to look for viral antibodies. HCV antibodies can be detected in the blood within 2 to 3 months after infection. If this test is positive, a confirmatory blood test would be ordered. An HCV viral load may be ordered to determine your chances for responding to treatment. In addition, HCV genotyping can help to guide the best treatment option and duration. Your doctor may also order liver function tests - AST, ALT and GGT tests - to monitor your liver's health.
A liver biopsy, usually performed as an outpatient surgical procedure, may be needed to determine the level of liver damage.
What Were the Standard HCV Treatments?
These treatments can cure roughly 70 percent of newly diagnosed cases, but patients must remain adherent with treatment and complete the full course of medications.
What Do Experts Suggest About Diagnosis and Treatment of HCV?
Increased rates of screening and diagnosis will likely result in accelerated demand for treatments. New oral treatments for HCV are expected to result in HCV cures for most newly diagnosed patients.
What's All the Buzz About New All-Oral HCV Treatments?
However, resistance can develop; therefore, two or more oral HCV drugs will be used together to help prevent resistance. Drug combinations tablets, like Viekira Pak and once-daily Viekira XR, are increasingly being approved. Side effect profiles are more tolerable than interferon - fatigue and headache are the most common side effects with many of the direct-acting oral antivirals, like Sovaldi, Harvoni, and Epclusa.
How Does Sovaldi Work in Hepatitis C Virus?
Many of the newer oral agents are known as a direct-acting agents (DAA), meaning that they interfere directly with the HCV life cycle by suppressing viral replication. Sovaldi and Harvoni, which is a combo drug that contains ledipasvir and sofosbuvir, are both given once-a-day.
What Evidence Supports the Sovaldi FDA-Approval?
Additionally, Sovaldi was effective in those who could not tolerate or take an interferon-based treatment regimen and in participants with liver cancer awaiting transplantation, addressing unmet medical needs.
Blockbuster Status: Solvadi and Harvoni
Harvoni contains sofosbuvir and the antiviral NS5A inhibitor ledipasvir. Harvoni - also a Gilead drug - hit mega-blockbuster status, too. Sales of Harvoni and Sovaldi in 2015 were tallied at $19.1 billion, over a 50% boost from the $12.4 billion in sales for 2014. New approvals, like Zepatier and Epclusa, may put pressure on sales of the originally-approved oral Hep C agents.
Safety and Effectiveness for All-Oral Treatments
However, study results with ribavirin-free treatment regimens using the all-oral sofosbuvir plus ledipasvir (Harvoni) have shown cure rates in 94 to 99% of patients within 12-24 weeks. Once-daily dosing, no ribavirin or interferon side effects, and less doctor visits are major advantages to ribavirin-free HCV regimens.
How Does Olysio Work in HCV?
Janssen’s Olysio is a second generation NS3/4A protease inhibitor and is intended to target genotype 1 HCV, the most common genotype of HCV. Other HCV protease inhibitors like boceprevir (Victrelis) are typically dosed three times a day - while Olysio is given once a day - which may improve compliance.
What Evidence Supports the FDA-Approval of Olysio?
Results from ASPIRE demonstrated that use of Olysio led to SVR24 in 65 percent of prior partial-responders and 53 percent of prior-null responders compared to 9% and 19% in the placebo groups, respectively.
The Olysio plus Sovaldi once-daily combo - for use in interferon- and ribavirin-free regimens for genotype 1 - was FDA-approved in 2014.
More Info: Olysio
Olysio is now approved to treat genotypes 1 or 4 AND patients with genotype 1 and co-infected with HIV. Treatments regimens vary based on patient characteristics. The all-oral Olysio plus Sovaldi regimen for HCV genotype 1 is given for either 12 weeks (without cirrhosis) or 24 weeks (with cirrhosis). In studies, common side effects for the two-drug regimen included fatigue, headache, nausea, trouble sleeping, and itching.
Other Safety Concerns for Olysio
Due to the possibility of birth defects, females and males must use two effective forms of birth control during treatment and for 6 months after treatment with Olysio, peginterferon alfa, and ribavirin combination therapy. Itching and nausea are other common side effects that may occur with Olysio.
Latest Approvals in HCV
In January 2016 the FDA approved Zepatier from Merck. Zepatier is a once-daily oral NS5A inhibitor (elbasvir) and NS3/4A protease inhibitor (grazoprevir) fixed-dose combination, used with or without ribavirin, for the treatment of HCV genotypes 1 and 4. In studies, sustained virologic response at 12 weeks ranged from 94 to 97 percent in genotype 1 and from 97 to 100 percent in genotype 4-infected subjects. Common side effects may included headache, stomach upset, and tiredness.
Daklinza (daclatasvir), from Bristol-Myers Squibb, received FDA approval in July 2015. Daklinza, an oral NS5A inhibitor used with sofosbuvir for the treatment of HCV genotype 1 or 3, was the first drug approved to treat genotype 3 HCV without need for interferon or ribavirin. In studies, 98 percent of the treatment-naive participants with no liver cirrhosis achieved sustained virologic response (a cure) with Daklinza + sofosbuvir for 12 weeks.
Other Oral Combo Approvals
Viekira Pak from AbbVie was approved in December 2014. It's used for treatment of genotype 1a and 1b HCV in patients with or without cirrhosis. Viekira Pak is an NS5A inhibitor (ombitasvir), NS3/4A protease inhibitor (paritaprevir), and CYP3A inhibitor (ritonavir) combination co-packaged with a non-nucleoside NS5B palm polymerase inhibitor (dasabuvir). Viekira Pak is not used in patients with moderate to severe hepatic impairment. Single tablet Viekira XR, containing all 4 ingredients, was approved in July 2016.
Technivie was FDA-approved in July 2015. It's an NS5A inhibitor (ombitasvir), NS3/4A protease inhibitor (paritaprevir), and CYP3A inhibitor (ritonavir) fixed-dose combination used with ribavirin. The Technivie plus ribavirin regimen is a 12-week regimen approved for genotype 4 HCV infections without the need for interferon. Technivie should not be used in patients with moderate to severe hepatic impairment.
Novel HCV Treatment: Epclusa
In studies, 95 to 99 percent of Epclusa-treated patients without cirrhosis or with mild cirrhosis had no virus detected in the blood 12 weeks after finishing the 12-week regimen. In patients with moderate to severe cirrhosis, some of whom required ribavirin, 94 percent were cleared of the virus 12 weeks after finishing treatment. The most common side effects of Epclusa include headache and tiredness. Epclusa is given once-daily in an oral, fixed-dose combination.
Costs of New HCV Treatments: How Will They Be Sustained?
Victrelis added $50,000 to costs with interferon and ribavirin. Sovaldi costs roughly $85,000 for a 12-week course, while Olysio is roughly $66,000 for 12 weeks. Harvoni, Gilead's all-oral combo drug that combines sofosbuvir and ledipasvir, has a price tag exceeding $94,000 per 12-week regimen. Insurance companies are obviously pushing back to treat only patients with advanced liver disease. Plus, lower-cost oral biosimilars for HCV won't appear for many years. But continued growth and competition in the HCV marketplace may help to lower drug prices.
HCV: Now and Later
In 2016, top-line treatments include Harvoni, Viekira Pak/ribavirin, Daklinza plus Solvadi, or Olysio plus Sovaldi for 12 weeks. Cure rates for these new regimens range between 80 and 100 percent, but cost and insurance coverage can be a barrier. Several manufacturers are also working on treatment regimens that last only 4 weeks, shaving 8 weeks off of therapy duration..
Finished: Oral Hepatitis C Treatments: The Evolving Landscape
- Centers for Disease Control and Prevention. Hepatitis C FAQs for the Public. Updated Jan. 8, 2016. Accessed 7/4/2016 at http://www.cdc.gov/hepatitis/hcv/cfaq.htm#cFAQ22
- Tse MT. All-oral HCV therapies near approval. Nature Reviews Drug Discovery. 2013;12:409-11. Accessed 7/4/2016 at http://www.nature.com/nrd/journal/v12/n6/full/nrd4036.html
- Hepatitis Central.com. Hepatitis C. Are there different types of hepatitis C? Accessed 7/4/2016 at http://www.hepatitiscentral.com/hepatitis-c/hepatitis-c-genotypes.html
- You DM, Pockros PJ. Simeprevir for the treatment of chronic hepatitis C. Expert Opin Pharmacother. 2013;14:2581-89. Accessed 7/4/2016.
- Drugs.com. New Drug Combo Helps Hard-to-Treat Hepatitis C. Accessed 7/4/2016 at https://www.drugs.com/news/new-combo-helps-hard-hepatitis-c-47015.html
- Press release. Olysio (simeprevir) received FDA approval for combination treatment of chronic hepatitis C. Johnson and Johnson. November 22, 2013. Accessed 7/4/2016 at http://www.jnj.com/news/all/OLYSIO-simeprevir-Receives-FDA-Approval-for-Combination-Treatment-of-Chronic-Hepatitis-C
- Drugs.com. FDA Advisory Committee Supports Approval of Gilead's Sofosbuvir for Chronic Hepatitis C Infection. Accessed 7/4/2016 at https://www.drugs.com/nda/sofosbuvir_131025.html.
- Pollack A. Hepatitis C, a Silent Killer, Meets Its Match. The New York Times. Health, November 4, 2013. Accessed 7/4/2016 at http://www.nytimes.com/2013/11/05/health/hepatitis-c-a-silent-killer-meets-its-match.html?_r=0
- Hep. Your Guide to Hepatitis. Hepatitis C: The Basics. Accessed 7/4/2016 at http://www.hepmag.com/articles/2512_18753.shtml
- Drugs.com. Experimental Hepatitis C Drug May Treat the Untreatable. Accessed 7/4/2016 at https://www.drugs.com/news/experimental-hepatitis-c-may-untreatable-48706.html
- Press Release. Gilead Announces New Sustained Viral Response Data for Sofosbuvir-Based Regimens in Genotype 3-Infected Hepatitis C Patients. Gilead. Accessed 7/4/2016 at http://www.gilead.com/news/press-releases/2013/11/gilead-announces-new-sustained-viral-response-data-for-sofosbuvirbased-regimens-in-genotype-3infected-hepatitis-c-patients.
- FDA Antiviral Drug Advisory Committee Meeting. October 24, 2013. Backgrounder package for NDA 205123. Simeprevir (TMC435). Accessed 7/4/2016 at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM371623.pdf.
- Press release. Gilead Announces Phase 3 Results for an All-Oral, Sofosbuvir-Based Regimen for the Treatment of Hepatitis C in Patients Co-Infected With HIV. November 2, 2013. Accessed 7/4/2016 at http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=1871556&highlight=
- Hernandez R. Janssen’s Simeprevir: Hep C Patients Hope It Is Worth the Wait. July 8, 2013. Specialty Pharmacy Times. Accessed 7/4/2016 at http://www.specialtypharmacytimes.com/news/Janssens-Simeprevir-Hep-C-Patients-Hope-It-Is-Worth-the-Wait