New anti-hepatitis C drug BMS-790052 does well in Phase IIa study

Michael Carter
Published:
20 September 2011

Up to 83% of individuals with chronic hepatitis C virus achieved a sustained virological response after receiving the investigational drug BMS-790052 in combination with pegylated interferon and ribavirin, results of a study presented to the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago show.

“In this Phase II study, adding BMS-790052 once daily to peginterferon alpha and ribavirin produced SVR [sustained virological response] rates and safety findings that warranted further development of BMS-790052,” said the study’s lead investigator, Prof. Stanislas Pol of the University of Paris V.

BMS-790052 belongs to a class of drugs called NS5A inhibitors and is the first anti-hepatitis agent in this class to be developed. The drug has achieved impressive four- and twelve-week treatment outcomes in earlier clinical studies and is taken orally once daily.

Glossary

erythropoietin

A natural hormone made in the kidneys to stimulate the production of red blood cells by the bone marrow.

The present Phase IIa study was designed to find a safe and effective dose to pursue in larger, Phase III randomised trials.

A total of 48 patients with chronic hepatitis C genotype-1 infection were recruited and they were randomised into four study arms. None of the patients had progressed to cirrhosis, and all were taking hepatitis C therapy for the first time.

All 48 participants received the current standard hepatitis C therapy – pegylated interferon plus weight-based ribavirin.

Patients in the control arm received this therapy in combination with a placebo. Individuals in the other arms received one of three once-daily doses of BMS-790052 (3mg, 10mg, 60mg). Treatment lasted 48 weeks.

The study endpoint was the proportion of patients who achieved a sustained virologial response – an undetectable hepatitis C viral load six months after the completion of therapy.

Data were also gathered on safety and side-effects.

Only a quarter of patients in the control arm achieved a sustained virological response. This compared to 42% of patients treated with the 3mg dose of BMS-790052, and 83% of individuals who received either the 10mg or 60mg dose.

Two patients (17%) in the control arm stopped their therapy because of side-effects. One patient (8%) in each of 3mg and 10mg groups also withdrew because of adverse events, as did four (33%) of the individuals treated with the 60mg dose of BMS-790052.

Overall rates of reported side-effects were similar across the four arms of the study.

One patient in each of the BMS-790052 study arms developed a serious side-effect, compared to none of the patients in the control arm.

Grade 3-4 (moderate to serious) on-treatment adverse events were reported by 42% of patients in the placebo arm, compared to 8% of individuals treated with the 3mg dose of BMS-790052, 25% of those receiving the 10mg dose, and a third of patients treated with the 60mg dose.

Approximately equal proportions of patients in each of the study arms developed anaemia, nausea, vomiting, neutropaenia and rash.

Supportive erythropoietin therapy was taken by two patients (17%) in the control arm, one individual (8%) in the 3mg arm, and by a quarter of patients in both the 10mg and 60mg groups.

“The hepatitis C treatment landscape is rapidly evolving and although there have been positive advances recently, there remains a need for additional therapies with a more favourable efficacy and treatment profile,” comment the investigators. “BMS-790052 in combination with pegylated interferon alpha and ribavirin achieves higher rates of cure than pegylated interferon plus ribavirin alone for subjects with HCV genotype 1 infection.”

Reference

Pol S et al. High rates of SVR24 for BMS-790052, a NS5A replication complex inhibitor, in combination with peg-IFN-alpha and ribavirin: a phase 2a trial in treatment-naïve HCV-genotype 1 subjects. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, abstract H2-800, Chicago, 2011. (Click here for the free abstract.)