Xigris still on track for US approval?

The split decision by a Food and Drug Administration advisory committeein its appraisal of Eli Lilly's candidate drug for sepsis, Xigris (drotrecogin alfa), reported briefly in the last issue of the Marketletter, does not necessarily mean that the agency will reject the drug, according to analysts.

At the committee meeting, panellists raised concerns about the efficacy and safety of the drug, specifically that it did not appear to work as well as hoped in patients with less severe sepsis. Reviewers suggested that, in some patients, Xigris performed no better than existing antibiotic-based therapy, while others questioned a protocol change in the middle of the main clinical trial of the drug which, it was alleged, may have exaggerated its efficacy.

Regarding safety, the panel was worried about newly-presented data indicating a 2.5% rate of intracranial hemorrhage seen in a compassionate-use program for the drug. ICH was also observed in Lilly's clinical trials program, but at a low incidence and with no difference between the Xigris and placebo groups. Some members of the panel suggested that Lilly should conduct additional clinical trials to elucidate the efficacy and safety issues further. However, it would be a serious setback for the firm if the agency made this a condition of approval, likely holding back a launch by around a year.