Back HCV Treatment Experimental HCV Drugs Sofosbuvir/Ledipasvir + Third Drug Cures Most HCV Patients in 6 Weeks

Sofosbuvir/Ledipasvir + Third Drug Cures Most HCV Patients in 6 Weeks

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A short and well-tolerated regimen of sofosbuvir, ledipasvir, and a third drug -- either GS-9669 or GS-9451 -- taken for as little as 6 weeks can cure a majority of previously untreated people with genotype 1 chronic hepatitis C, including those with traditional predictors of poor response, according to study results published in the January 12 advance edition of The Lancet.

While most clinical trials of new hepatitis C drugs have been done by pharmaceutical companies, the National Institutes of Allergy and Infectious Diseases (NIAID) is conducting a series of studies among underserved urban populations, looking for simple and tolerable treatment for people prone to difficulties with adherence and side effects. Cutting down treatment duration as much as possible would improve convenience as well as cut costs.

Anita Kohlifrom the National Institutes of Health and fellow researchers with the Phase 2a SYNERGY study (NCT01805882) evaluated interferon- and ribavirin-free oral regimens using a fixed-dose coformulation of Gilead Sciences' nucleotide HCV polymerase inhibitor sofosbuvir and HCV NS5A inhibitor ledipasvir (Harvoni) plus a third investigational direct-acting antiviral that works by a different mechanism -- either the non-nucleoside polymerase inhibitor GS-9669 or the HCV protease inhibitor GS-9451.

This trial enrolled 60 mostly previously untreated chronic hepatitis C patients in Washington, DC, between January and December 2013. About 70% were men, around 90% were African-American, and 70% had hard-to-treat HCV subtype 1a. About one-quarter had advanced liver fibrosis or cirrhosis (stage F3-F4), but people with cirrhosis were excluded from the 6-week arms. People with hepatitis B or HIV coinfection were also excluded.

Participants in this open-label, non-blinded study were sequentially assigned to receive sofosbuvir/ledipasvir for 12 weeks, sofosbuvir/ledipasvir plus GS-9669 for 6 weeks, or sofosbuvir/ledipasvir plus GS-9451 for 6 weeks.

The primary endpoint was sustained virological response, or continued undetectable HCV viral load at 12 weeks after completing treatment (SVR12). Kohli previously presented these findings in part at the 2014 Conference on Retroviruses and Opportunistic Infections.

Results

  • 100% of participants in the sofosbuvir/ledipasvir 12-week arm achieved SVR12.
  • 95% of patients who received receive sofosbuvir/ledipasvir + GS-9669 for 6 weeks achieved SVR12, with 1 person relapsing 2 weeks after finishing treatment.
  • Likewise, 95% of patients who received sofosbuvir/ledipasvir + GS-9451 for 6 weeks achieved SVR, with 1 person lost to follow-up after reaching SVR4 at 4 weeks post-treatment.
  • All regimens were generally safe and well-tolerated.
  • The most common adverse events were headache, fatigue, and diarrhea, mostly mild.
  • There were 2 serious adverse events deemed unrelated to study drugs (pain after a post-treatment liver biopsy and vertigo).
  • No participants discontinued treatment due to adverse events.

"In this small proof-of-concept study, 2 different 3-drug regimens that were given for 6 weeks resulted in high cure rates for HCV infection with excellent tolerability," the study authors concluded. "Addition of a third potent direct-acting antiviral drug can reduce the duration of treatment required to achieve sustained viral response in patients with chronic HCV genotype 1 infection without cirrhosis."

"This short duration, simple therapy for HCV may prove relevant for the global elimination of hepatitis C, where simple, well-tolerated therapy of short duration is required to ensure adherence," they added.

1/21/15

Reference

A Kohli, A Osinusi, Z Sims, S Kottilil, et al. Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study. The Lancet 6736(14):61228-61229. January 12, 2015 (Epub ahead of print).

GR Foster. Shorter treatments for hepatitis C: another step forward? (Comment). The Lancet 6736(14):61600-61607. January 12, 2015 (Epub ahead of print).

Other Source

NIAID. High Hepatitis C Cure Rate Seen in Trial of 6-Week Oral Drug Regimens. NIH News press release. January 12, 2015.