Hep C Drug Pipeline: New Additions and Three Combos to Watch for in 2014
Analysts believe that 2014 will be a tremendous year for advancements in Hepatitis C therapy. Excitement is growing as we inch closer to approval for an improved, highly effective, safer drug combination that experts say could cure many people of Hepatitis C.
For the most common strain in the U.S., Hepatitis C genotype 1, the current standard therapy generally combines three drugs:
- pegylated interferon
- a direct acting antiviral (DAA)
Direct acting antivirals are medications that attack the ability of the Hepatitis C virus to replicate. Different DAA’s interfere with the Hepatitis C replication cycle at different stages. Telaprevir (Incevik) and boceprevir (Victrelis) are protease inhibitors – one type of DAA. Although adding one of these protease inhibitors to interferon and ribavirin treatment boosts treatment success from 50 percent up to 75 percent effectiveness, they are both associated with some extremely distressing side effects including anemia, rash, anal itching and rectal burning.
The greatest promise for improved treatment regimens lies with an interferon-free Hepatitis C drug protocol. Primarily because interferon is associated with so many severe side effects, the race for an approved, interferon-free, Hepatitis C regimen is heated. Interferon-free regimens are expected to have a higher success rate, be better tolerated and enable treatment of people who cannot take interferon. The most substantial breakthroughs for Hepatitis C treatment seem to revolve around DAA cocktails, with drug resistance posing the biggest challenge. Hence, experts believe a cure lurks in finding just the right mixture of DAA’s without interferon.
At the end of 2013, two new DAA’s were approved, both of which were approved by the FDA in conjunction with pegylated interferon and ribavirin for treating Hepatitis C genotype 1. They are:
- Olysio (simeprevir) – Approved by the FDA in November 2013, simeprevir is an NS3/4A protease inhibitor made by Janssen Pharmaceuticals. Simeprevir requires 12 weeks of triple therapy and 12 weeks of double therapy (just interferon and ribavirin). With an effectiveness of around 80 percent, simeprevir’s main side effect is rash and photosensitivity.
- Sovaldi (sofosbuvir) – Approved by the FDA in December 2013, sofosbuvir is a polymerase inhibitor made by Gilead Sciences. Sofosbuvir requires just 12 weeks of treatment and has an estimated 90 percent success rate.
Unfortunately, both simeprevir and sofosbuvir are currently dependent on interferon for treating Hepatitis C genotype 1.
Three of the interferon-free, DAA drug combinations that are currently in Phase III trials at the end of 2013 include:
- Abbott/Enanta Combo – This triple combination involves ABT-450 (a protease inhibitor), ABT-267 (an NS5A inhibitor) and ABT-333 (a polymerase inhibitor). Preliminary results indicate after 12 weeks with ribavirin, 96 percent of treatment-experienced patients with genotype 1 had a successful outcome.
- Boehringer Ingelheim – Boehringer Ingelheim’s faldaprevir (protease inhibitor) and deleobuvir (polymerase inhibitor) are also combined with ribavirin in Phase III trials. Faldaprevir has proven to be effective against a relatively common, yet troublesome, Hepatitis C variant known as the Q80K mutant. While Phase II trials delivered success rates around 85 percent (even on patients with cirrhosis), interim results for the Phase III trials have not been made public yet.
- Gilead – Sofosbuvir (polymerase inhibitor) was just approved by the FDA in December 2013 in combination with pegylated interferon and ribavirin, but it is also in an interferon-free Phase III trial with ledipasvir (NS5A inhibitor). Without interferon or ribavirin, preliminary results demonstrate that sofosbuvir and ledipasvir have cure rates well over 90 percent in as few as 8 weeks. A previous study of sofosbuvir, ledipasvir and ribavirin showed a 100 percent Hepatitis C success rate.
While there are many more drug combinations being studied, these three appear to be the most advanced as we start the New Year. Many people have chosen to wait until better Hepatitis C treatment options become available, and it seems that 2014 might be ushering in those improvements. With the right combination of DAA’s, a safe, effective treatment without interferon appears close. We expect great things from Abbott and Enanta, Boehringer Ingelheim and Gilead (as well as a long list of other potential contenders), and are looking forward to turning the corner on Hepatitis C – so it can officially be rendered a curable illness.
http://blogs.hepmag.com/lucindakporter/2013/10/a_bright_future_for.html, A Bright Future for Hepatitis C Patients, Lucinda K. Porter, RN, Retrieved December 29, 2013, Smart + Strong, 2013.
http://consumer.healthday.com/infectious-disease-information-21/hepatitis-news-373/new-hepatitis-c-drug-approved-682860.html, New Hepatitis C Drug Approved by FDA, Retrieved December 29, 2013, HealthDay, 2013.
http://hcvadvocate.blogspot.ca/p/quick-reference-guide_21.html, Quick Reference Guide DAA’s, Retrieved December 29, 2013, Hepatitis C Support Project, 2013.
http://hepatitiscnewdrugs.blogspot.com/2013/12/gileads-sofosbuvir-and-ledipasvir.html, Gilead’s Sofosbuvir and Ledipasvir Outstanding Late-stage Hepatitis C Data, Retrieved December 29, 2013, hepatitiscnewdrugresearch.com, 2013.
http://hepatitiscnewdrugresearch.com/quick-facts–direct-acting-antivirals-telaprevirboceprevir.html, Quick Facts – Victrelis/Boceprevir, Incevik/Telaprevir, Retrieved December 29, 2013, hepatitiscnewdrugresearch.com, 2013.
http://ir.enanta.com/phoenix.zhtml?c=147990&p=irol-newsArticle&ID=1883481, Enanta Pharmaceuticals Announces 96 Percent SVR12 in Treatment Experienced Genotype 1 Hepatitis C Patients in Sapphire-11 Study, Retrieved December 29, 2013, Enanta Pharmaceuticals, 2013.
http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2013/15_august_2013_hcv.html, Boehringer Ingelheim announces full patient enrolment for two of its pivotal Phase III interferon-free hepatitis C clinical trials, Retrieved December 29, 2013, Boehringer Ingelheim, 2013.
http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2013/16_december_2013hcv.html, Hepatitis C: Phase III data show Boehringer Ingelheim’s faldaprevir* is effective even in patients with common drug-resistant viral variant, Retrieved December 29, 2013, Boehringer Ingelheim, 2013.
http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm376449.htm, FDA Approves New Treatment for Hepatitis C Virus, Retrieved December 27, 2013, US Food and Drug Administration, 2013.
http://www.fiercebiotech.com/press-releases/first-interferon-free-regimens-treatment-hepatitis-c-virus-are-expected-lau, The First Interferon-Free Regimens for Treatment of Hepatitis C Virus Are Expected to Launch in 2014 in the United States and Europe and Will Experience Aggressive and Widespread Uptake Through 2021, Retrieved December 29, 2013, FierceMarkets, 2013.
http://www.gilead.com/news/press-releases/2013/4/data-from-phase-3-studies-of-gileads-sofosbuvir-for-hepatitis-c, Data from Phase 3 Studies of Gilead’s Sofosbuvir for Hepatitis C To Be Presented at 48th Annual EASL Meeting; Findings Published Online Today in The New England Journal of Medicine, Retrieved December 29, 2013, Gilead, 2013.
http://www.medscape.com/viewarticle/777475_2, Current Prospects for Interferon-free Treatment of Hepatitis C in 2012, Catherine AM Stedman, Retrieved December 29, 2013, WebMD, LLC, 2013.
http://www.medscape.com/viewarticle/813197, FDA Panel Recommends Approval of Simeprevir for Hepatitis C Troy Brown, RN, Retrieved December 29, 2013, WebMD, LLC, 2013.
http://www.natap.org/2013/CROI/croi_07.htm, ELECTRON: 100% SVR Rate for Once-Daily Sofosbuvir Plus Ledipasvir Plus Ribavirin Given for 12 Weeks in Treatment-Naïve and Previously Treated Patients With HCV GT 1, Jules Levin, Retrieved December 29, 2013, 20th Conference on Retroviruses and Opportunistic Infections, 2013.
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