Shares in US biopharma company Chimerix lost three quarter of their value after it revealed a late-stage study of antiviral drug brincidofovir failed to meet its objectives.
The phase III trial of the drug - a treatment for cytomegalovirus (CMV) infections in people undergoing stem cell transplants to repopulate bone marrow - was unable to show a significant reduction in infections in the 24 weeks after the transplant procedure.
Chimerix said it was determined to press on with the drug's development, however, saying it believes there is still a "viable path forward" for the nucleotide analogue.
Brincidofovir appeared to protect patients from infections during the first 10 weeks of the SUPPRESS study, where it was being administered as an oral therapy once-daily, outperforming placebo during this period.
After treatment stopped however there was a higher level of infections in the brincidofovir group, negating its earlier advantage.
Patients in the brincidofovir arm also showed an increase in mortality compared to the control arm, but the increase was not statistically significant, according to Chimerix.
In a statement, Chimerix said preliminary suggestions are that the disappointing performance was linked to confirmed cases of graft-versus-host-disease (GVHD) - when the transplanted immune cells start to attack the patient. These resulted in a significantly higher use of corticosteroids in the brincidofovir group compared to the control arm.
"Both GVHD and use of corticosteroids are risk factors for 'late' CMV infection that occurs after discontinuation of the antiviral," said Chimerix.
The company now plans to discuss the data with the FDA and other regulatory authorities as it works out the best way to proceed with the brincidofovir programme, but for the time being has halted enrolment of the drug in two other trials involving kidney transplant patients.
It said it is continuing to carry out trials of the drug in the treatment of adenovirus and smallpox "as well as use in other populations in need of a novel compound for DNA viral infections". It has also been tested as an Ebola treatment.
Despite the brave face, it is clear that the trial failure is a big blow to the company, as brincidofovir had been predicted by some analysts to clear in excess of $2bn in annual sales at peak.
Brincidofocvir's failure in the stem cell transplant cell trial could hand an opportunity for Astellas and Vical, which are developing a DNA-based vaccine against CMV - called ASP0113 - for use in this setting.