Review of BMS-986094 Finds Alarming Rate of Cardiotoxicity

In 2012, a clinical trial for the investigative hepatitis C drug BMS-986094 was terminated following the death of a patient.

A retrospective review of a phase 2 trial for the drug has found that rates of cardiotoxicity associated with the drug may be as high as 40 percent.

What is BMS-986094?

BMS-986094 was a nucleotide-polymerase inhibitor being tested in combination with a number of different drugs, including Daclatasvir, as a treatment for chronic hepatitis C (HCV) infection. However, in August 2012, Bristol-Myers Squibb terminated development for the drug after a 25-year-old patient developed rapidly progressive heart failure and died.

The termination of BMS-986094 sent a shock wave through HCV drug development, resulting in the clinical hold and eventual scrapping of similar compounds, including Idenix’s IDX184 and IDX19368.

A new retrospective review assessing that adverse events associated with BMS-986094 has been published in the journal Hepatology and provides new insight into the cardiotoxicity associated with the compound.

BMS-986094 Associated with Cardiotoxicity in 40% of Patients

• According to Medscape, 14 of the 34 patients treated with BMS-986094 during a phase 2 clinical trial testing the drug’s efficacy and safety had some evidence of cardiac dysfunction in one or more evaluations in the six months following termination of the drug’s development.
  • Six patients were diagnosed with severe left ventricular dysfunction.
  • Eight had moderate left ventricular dysfunction.
• Investigators also noted that the 20 patients who had received 200 mg of BMS-986094, four had developed sever systolic dysfunction and another seven showed moderate dysfunction. By comparison, of the nine patients that received a 100 mg dose, two were diagnosed with severe systolic dysfunction and one developed moderate impairment.
• None of the patients in the 50 mg arm developed systolic dysfunction.