BMS drops HCV drug after death
This article was originally published in Scrip
Bristol-Myers Squibb has discontinued development of BMS-986094 (BMS-094, formerly known as INX-189). The nucleotide polymerase (NS5B) inhibitor, which was in Phase II development for the treatment of hepatitis C, was the driver behind BMS' $2.5 billion acquisition of Inhibitex at the start of this year (scripintelligence.com, 9 January 2012).
BMS made the decision "in the interest of patient safety, based on a rapid, thorough and ongoing assessment of patients". The company voluntarily suspended the Phase II trial at the beginning of the month (scripintelligence.com, 2 August 2012) following a case of heart failure which subsequently resulted in death. That suspension caused BMS stock to lose around $3 billion in market value. The US FDA subsequently placed the compound on clinical hold.
BMS said it is working in collaboration with the FDA and clinical study investigators to conduct comprehensive assessments and follow-ups of all BMS-986094 study patients. "To date, nine patients have been hospitalised, including the initial patient; two patients remain hospitalised," noted the company. "While the cause of these unexpected events, which involve heart and kidney toxicity, has not been definitively established, the company has determined that it is in the best interest of patients to halt development of BMS-986094."
BMS said it is committed to investigating the safety issue further, including studies to evaluate the potential mechanism of the toxicity.
The nucleotide polymerase inhibitor class of drugs for hepatitis C, dubbed 'nucs', were highly desired in the space, and a number of BMS' competitors have their own in development. These include Gilead Sciences with the most advanced nuc, GS-7977, which is in multiple Phase III studies. Gilead paid an eye-watering $11 billion for the product candidate and other hepatitis assets when it acquired Pharmasset at the end of last year (scripintelligence.com, 21 November 2011).
However, following BMS' setback, there are concerns the cardiac issues are a class-wide problem. Idenix Pharmaceuticals has borne the brunt of these worries. On 16 August, the US FDA put its nuc for the treatment of hepatitis C under a partial clinical hold. Idenix has been forced to halt its Phase IIb trial of IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV) while the FDA looks into the data obtained so far.
Idenix CEO Ronal Renaud insisted "there has been no evidence to date of cardiotoxicity" in patients dosed with IDX184 and PegIFN/RBV beyond that seen with PegIFN/RBV alone (scripintelligence.com, 17 August 2012). He added that there are "significant differences" between IDX184 and BMS-094 – insisting his firm has taken an entirely different prodrug approach with its experimental nuc.
Other competitors in the hepatitis C space with nucs in development include Vertex Pharmaceuticals and Achillion Pharmaceuticals, which so far have remain unscathed.