May 30, 2014
So far, it's been a breakthrough year for hepatitis C virus (HCV) treatment, with many new drugs coming into the spotlight as more effective and safer options to treat and cure HCV, which until recently required 12 weeks or more of weekly injections that didn't always cure the infection. Here's an overview of some of the top studies that have come out thus far in 2014.
Researchers saw 95%-100% HCV cure rates, using a six-week course of three oral medications, in a study presented by Anita Kohli, M.D., at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014). Participants were assigned to one of the three study arms: dual therapy with sofosbuvir (Sovaldi)/ledipasvir for 12 weeks, or sofosbuvir/ledipasvir plus either GS-9669 (a non-nucleoside NS5B site 2 polymerase inhibitor) or GS-9451 (an NS3 protease inhibitor) for six weeks.
The 12-week post-treatment sustained virological response (SVR12) rate, which is a measure of treatment success, was between 95% (for those taking sofosbuvir/ledipasvir and GS-9669) and 100% (in the two other arms).
"This short duration, simple therapy for HCV may prove relevant for the global elimination of hepatitis C, where uncomplicated, well-tolerated therapy is required to ensure adherence and minimize health care expenditures," the researchers concluded. Future studies will evaluate the effectiveness of a four-week regimen of three oral drugs.
At least 99% of previously untreated people with genotype-1b HCV infection (the most common type of HCV) were cured, after undergoing a 12-week course of three direct-acting antivirals, according to a study presented by Rajender Reddy, M.D., at CROI 2014.
The study, known as PEARL III, followed 419 treatment-naive patients with HCV genotype 1b, who all received the triple-drug, fixed-dose combination known as 3D for 12 weeks and were randomized to also receive either ribavirin (210 patients) or a placebo (209 patients).
Using the cure measure of SVR12, over 99% of participants in both arms were cured. Additionally, treatment was well tolerated and there were no discontinuations due to adverse events. The researchers concluded that a 12-week course of 3D is highly safe and effective for patients living with genotype-1b HCV. AbbVie, the company behind the drug, submitted 3D to the U.S. Food and Drug Administration (FDA) for approval on April 22.
An all-oral regimen of daclatasvir, asunaprevir and BMS-791325, led to SVR12 rates of over 90% for previously untreated HCV patients with genotype 1a, one of the hardest-to-treat subtypes of HCV, according to a study presented at CROI 2014.
The study followed 166 patients who were randomized to receive 30 mg of daclatasvir, 200 mg of asunaprevir, and either 75 mg or 150 mg of BMS-791325, all taken twice-daily for 12 weeks. "For people with HCV subtype 1a, the SVR12 rate was 91% using either the 75 mg or 150 mg BMS-791325 dose; for people with subtype 1b, SVR12 rates were 100% and 94%, respectively," as reported by HIVandHepatitis.com.
The regimen was generally safe and well tolerated and is now being studied in phase-3 trials as a fixed-dose coformulation. Daclatasvir is also being studied in people living with HIV/HCV coinfection.
A 24-week regimen of sofosbuvir plus ribavirin cured 93% of people with HCV genotype 4, another hard-to-treat subtype of HCV, although treatment for only 12 weeks was not as effective, according to a poster presented at the 49th International Liver Congress (EASL 2014).
The study followed 60 Egyptian patients, all of whom completed treatment, which was generally safe and well tolerated. The participants were randomized to receive 400 mg of once-daily sofosbuvir plus 1,000-1,200 mg of ribavirin for either 12 or 24 weeks.
- SVR12 rates were 68% in the 12-week treatment arm and 93% in the 24-week arm.
- Among treatment-naive participants, the 12- and 24-week SVR12 rates were 70% and 100%, respectively.
- Among treatment-experienced patients, SVR12 rates were 59% and 87%, respectively.
Sofosbuvir was approved by the FDA last December, although Gilead, the drug's manufacturer, continues to receive backlash for the regimen's high price tag of $1,000 a pill.
In April, the European Association for the Study of the Liver (EASL) issued new guidelines for the treatment of HCV in Europe, recommending the newest direct-acting antivirals, with a "mix-and-match" approach to get the most effective regimens.
The guidelines make recommendations for all HCV genotypes, and include all direct-acting antivirals that are expected to be licensed in Europe during 2014, including the HCV protease inhibitor simeprevir and the NS5A inhibitor daclatasvir. Simeprevir is likely to receive marketing approval in May 2014 and daclatasvir in September 2014. Sofosbuvir was already approved in January 2014.
HIVandHepatitis.com also writes:
The guidelines move beyond U.S. recommendations issued in January, which incorporated a small number of off-label uses not included in the FDA licenses for sofosbuvir (Sovaldi) and simeprevir (Olysio). The new EASL guidelines also include daclatasvir, a NS5A inhibitor that is likely to receive approval in Europe later this year.
The complete guidelines can be found at the EASL website.
Warren Tong is the research editor for TheBody.com and TheBodyPRO.com.
Follow Warren on Twitter: @WarrenAtTheBody.
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