- Category: Experimental HCV Drugs
- Published on Monday, 04 March 2013 00:00
- Written by Liz Highleyman
An interferon-free regimen of the direct-acting hepatitis C drugs sofosbuvir (formerly GS-7997), ledipasvir (formerly GS-5885), and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1, according to data presented today at the 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013) in Atlanta.
Direct-acting antiviral agents that target different steps of the hepatitis C virus (HCV) lifecycle have ushered in a new era of treatment, but many patients and providers are awaiting all-oral therapy that avoids interferon and its difficult side effects.
Edward Gane from Auckland Clinical Studies presented the latest data from the ELECTRON trial, sponsored by Gilead Sciences. ELECTRON investigators initially tested a simple 12-week regimen of Gilead's once-daily nucleotide analog HCV polymerase inhibitor sofosbuvir plus 1000-1200 mg weight-based ribavirin for previously untreated people with easier to treat HCV genotypes 2 or 3. As reported at the 2011 AASLD Liver Meeting, that regimen cured 100% of these patients.
The ELECTRON researchers then looked at genotype 1 patients, both treatment-naive and null responders to previous interferon-based therapy. As Gane reported at last year's Retrovirus conference, sofosbuvir/ribavirin alone was not adequate for this more difficult-to-treat population. While participants saw a rapid decline in HCV RNA and had undetectable viral load at the end of therapy, some treatment-naive patients and almost all prior null responders relapsed, resulting in cure rates of 84% and 10%, respectively.
The investigators then asked whether adding a second direct-acting agent -- Gilead's NS5A replication complex inhibitor ledipasvir -- could increase cure rates for genotype 1 patients. Studies to date have shown that drugs in this class are highly potent and well-tolerated.
The analysis included 25 treatment-naive participants and 9 prior null responders. Two-thirds of the naive participants were women, while 78% of the experienced patients were men. About 90% were white and the average age was about 48 years. Most had unfavorable IL28B gene patterns (only one-third of the treatment-naive and none of the experienced patients had the favorable CC pattern associated with good interferon response). More than 80% had the more difficult-to-treat HCV subtype 1a and baseline HCV RNA levels were high.
- After 4 weeks on treatment, all naive patients and all but 1 null responder had rapid virological response (RVR).
- By the end of the 12-week course of therapy, the remaining null responder also achieved viral suppression, yielding end-of-treatment response rates of 100% for both groups.
- At both 4 and 12 weeks post-treatment, all participants in both groups maintained undetectable HCV RNA; SVR12 is considered a cure.
- The triple combination regimen was generally safe and well-tolerated.
- 2 people (8%) experienced serious adverse events and 1 person (4%) stopped treatment for this reason.
- The most common adverse events were anemia (20%), depression (8%), and headache (4%).
- About 44% experienced grade 3 laboratory abnormalities including anemia.
Based on these findings, the ELECTRON researchers concluded, "Adding ledipasvir increased the efficacy of sofosbuvir + ribavirin."
Gilead is currently testing a fixed-dose coformulation containing sofosbuvir and ledipasvir in a Phase 3 trial. Investigators will also look at a dual combination of sofosbuvir plus ledipasvir without ribavirin, as adding ledipasvir lowers the risk of relapse and may make ribavirin unnecessary for some or all patients.
E Gane, R Hyland, X Ding, et al. ELECTRON: 100% Suppression of Viral Load through 4 Weeks’ Post-treatment for Sofosbuvir + Ledipasvir (GS-5885) + Ribavirin for 12 Weeks in Treatment-naïve and -experienced Hepatitis C Virus GT 1 Patients. 20th Conference on Retroviruses and Opportunistic Infections. Atlanta, GA, March 3-6, 2013. Abstract 41LB.