AstraZeneca will have carry out an additional Phase II dose-ranging study – before embarking on its already-planned Phase III trial – in order to bring sepsis candidate CytoFab before the scrutiny of the world’s regulatory authorities.
Discussions with regulators in the USA and EU confirmed that a single Phase III study of CytoFab (polyclonal ovine anti-TNF antibody fragments) would be sufficient for approval, but concluded this should be backed up by another Phase II study that will help AstraZeneca gauge more accurately how many patients will be required, confirm the best dose and provide supportive safety and efficacy data.
While AstraZeneca said the chances of a successful outcome will be enhanced by this strategy, the requirement for a Phase II trial will extend the expected development time for the drug significantly.
News of the delay had an immediate impact on Protherics’ shares, which were down more than 5% in mid-morning trading to 82 pence on the London Stock Exchange.
The Phase II trial of CytoFab, licensed from UK company Protherics in a £195 million deal in December 2005, will get underway in the second half of next year and take a little under two years (21 months) to complete. It will immediately be followed by the Phase III trial, which will take place in the USA, Europe and Japan.
In September, Protherics reported positive Phase IIb data on CytoFab and suggested that AstraZeneca would embark on a Phase III programme in 2007.
Sepsis - a severe illness caused by overwhelming infection of the blood by toxin-producing bacteria - remains one of the greatest unmet needs in medicine, but efforts by the drug industry to develop effective treatments have been met with disappointment, with a raft of clinical candidates failing in the latter stages of development.
At present, the only drug that has been approved for sepsis, despite decades of research and dozens of clinical candidates, is Eli Lilly's Xigris (drotrecogin alfa). This product is recommended only for patients with the most severe forms of the disease, and has failed to meet its once-predicted blockbuster status.