Multiple-DAA regimens may decrease duration of HCV treatment

WASHINGTON — Use of multiple direct-acting antivirals targeting various stages of the hepatitis C life cycle can effectively reduce the length of HCV treatment and produce high rates of sustained virologic response 4 weeks after end of treatment, a speaker said here.

“The study is at least suggestive that a shorter combination of treatment is possible if you combine potent DAAs [direct-acting antivirals],” Anita Kohli, MD, of Science Applications International Corp. and the National Institute of Allergy and Infectious Diseases, said in discussing a late-breaking poster at The Liver Meeting. “Really defining that threshold of how long you need to treat patients with combination DAA therapy has not been determined yet.”

The ongoing phase 2 clinical trial enrolled 60 treatment-naive HCV genotype 1 patients into three arms. Arm A (n=20) was treated with 400 mg sofosbuvir and 90 mg ledipasvir daily in fixed-dose combination for 12 weeks. Arm B (n=20) received the same combination of sofosbuvir and ledipasvir plus 500 mg GS-9669, a non-nucleoside NS5B inhibitor, daily for 6 weeks. Arm C (n=20) received the same sofosbuvir/ledipasvir combination and 80 mg GS-9451, an HCV protease inhibitor, daily for 6 weeks.

All patients achieved end-of-treatment response rates of HCV RNA below the lower limit of quantification. All arm A patients also achieved sustained virologic response at week 12.

SVR 12 numbers for arms B and C are not available yet, but all patients in arm C achieved SVR4. Eighteen arm B patients achieved SVR4; one patient relapsed after stopping therapy and one patient who achieved SVR2 missed his 4-week follow-up.

“I think clinicians can look at this and certainly be hopeful that moving forward we will be able to treat patients who have historically poor prognostic factors for response to interferon-based treatment with very short regimens that, in small trials, have shown promising adverse-effect profiles,” Kohli said.

Disclosure: Kohli reports no relevant financial disclosures.

For more information:

Kohli A. #LB-8: Combination Oral, Ribavirin Free, Antiviral Therapy to Optimize Treatment Outcomes for Hepatitis C GT-1 Treatment-Naive Patients: Interim Results from the NIAID SYNERGY Trial. Presented at: The Liver Meeting 2013; Nov. 1-5, Washington.