HCV nucleotide analogue polymerase inhibitor associated with cardiac dysfunction

Fourteen of 34 patients with hepatitis C virus infection who were treated with the novel nucleotide analogue polymerase inhibitor BMS-986094 had some evidence of cardiac dysfunction, according to a new report.

BMS-986094 (Bristol-Myers Squibb) was developed as a treatment for HCV, but clinical development was discontinued in 2012.

“Treatment for chronic HCV infection is evolving from interferon-based therapy to direct-acting antiviral agents, yet some safety concerns have arisen involving cardiac toxicity,” Tariq Ahmad, MD, MPH, and colleagues wrote.

To assess potential off-target toxicities of new DAAs, the researchers conducted a retrospective evaluation of the sentinel case in a phase 2 study which led Bristol-Myers Squibb to cease clinical development of BMS-986094 and outcomes of other patients in the same study, such as electrocardiograms, transthoracic echocardiograms and cardiac biomarkers.

According to the findings, 34 patients with HCV received interferon-free BMS-986094 regimens. In total, six patients had left ventricular ejection fraction (LVEF) <30% and eight had LVEF 30% to 50%.

Suspected cardiotoxicity requiring hospitalization was reported in 11 patients.

After a median of 20 days, six patients with LVEF <50% experienced normalization of systolic function. The most sensitive predictor of LVEF dysfunction was T-wave inversions, Ahmad and colleagues reported. When the researchers performed pathological analysis of cardiac tissue, they found severe myocyte damage with elongated myofibrils without gross necrosis, according to the study.

“These findings were consistent with some results of recent primate studies that were conducted to further investigate the potential mechanisms of BMS-986094 toxicity,” the researchers wrote. “Ongoing surveillance of DAAs for cardiotoxicities may be beneficial, especially among patients at higher risk for cardiovascular disease.”

Disclosure: See the full study for a list of relevant financial disclosures.

Fourteen of 34 patients with hepatitis C virus infection who were treated with the novel nucleotide analogue polymerase inhibitor BMS-986094 had some evidence of cardiac dysfunction, according to a new report.

BMS-986094 (Bristol-Myers Squibb) was developed as a treatment for HCV, but clinical development was discontinued in 2012.

“Treatment for chronic HCV infection is evolving from interferon-based therapy to direct-acting antiviral agents, yet some safety concerns have arisen involving cardiac toxicity,” Tariq Ahmad, MD, MPH, and colleagues wrote.

To assess potential off-target toxicities of new DAAs, the researchers conducted a retrospective evaluation of the sentinel case in a phase 2 study which led Bristol-Myers Squibb to cease clinical development of BMS-986094 and outcomes of other patients in the same study, such as electrocardiograms, transthoracic echocardiograms and cardiac biomarkers.

According to the findings, 34 patients with HCV received interferon-free BMS-986094 regimens. In total, six patients had left ventricular ejection fraction (LVEF) <30% and eight had LVEF 30% to 50%.

Suspected cardiotoxicity requiring hospitalization was reported in 11 patients.

After a median of 20 days, six patients with LVEF <50% experienced normalization of systolic function. The most sensitive predictor of LVEF dysfunction was T-wave inversions, Ahmad and colleagues reported. When the researchers performed pathological analysis of cardiac tissue, they found severe myocyte damage with elongated myofibrils without gross necrosis, according to the study.

“These findings were consistent with some results of recent primate studies that were conducted to further investigate the potential mechanisms of BMS-986094 toxicity,” the researchers wrote. “Ongoing surveillance of DAAs for cardiotoxicities may be beneficial, especially among patients at higher risk for cardiovascular disease.”

Disclosure: See the full study for a list of relevant financial disclosures.