AstraZeneca has joined the ranks of pharmaceutical companies hoping to develop a treatment for sepsis, signing a £195 million deal to license rights to CytoFab, a drug developed by UK company Protherics.
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.
CytoFab is just about to start a Phase III trial in severe sepsis which should be enough to support approval, according to the UK firm.
Under the terms of the agreement, AstraZeneca will pay an upfront fee of £16.3 million, as well as a £7.5 million equity investment in Protherics at a 30% premium to its recent share price. The balance of the £195 million will come from milestones payments, mostly before approval of the drug. Protherics will also be entitled to a royalty rate on sales of 20%.
CytoFab is a polyclonal antibody against tumor necrosis factor alpha, which is produced in vast quantities in sepsis patients and contributes to the symptoms and organ dysfunctions that eventually kill the patient. Phase IIb results showed that CytoFab significantly reduced TNF-alpha in the blood and lung tissues of sepsis patients, and patients required five days' less mechanical ventilation than when treated with placebo. There was also a trend towards improved survival; approximately one third of patients with severe sepsis die from major organ failure at present.
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.
Third-quarter sales were just $32 million dollars, down 8%, reflecting recent trial data indicating that it has little benefit in patients who are not at very high risk of death, and is also associated with a lower survival rate in some sepsis patients.
Meanwhile, other companies developing drugs to treat sepsis include: Eisai, whose endotoxin antagonist E5564 (eritoran) recently cleared a Phase II study for severe sepsis and will be advanced into Phase III development; Takeda, which has started clinical trials of TAK-242, which inhibits Toll-like receptor 4; and Merck & Co/BioXell, which have compounds that affect the white blood cell receptor TREM-1 in early-stage development.
- Protherics also reported its interim results today, recording an operating loss of £3.6 million on sales that were flat at £10.7 million. In dollar terms, Protherics’ marketed products - snake antivenoms CroFab and ViperaTAb and digoxin overdose treatment DigiFab - saw sales up 9% in US dollar terms to $18.1 million.