CytoFab™ for severe sepsis
Please click here for a PDF of the CytoFab™ fact sheet.
Please click here for a PDF of the Sepsis fact sheet.
CytoFab™ is a polyclonal antibody based product designed to neutralise tumour necrosis factor alpha (TNF-α) and is being developed as a treatment for severe sepsis. The body's response following severe infection often involves the release of high levels of molecules called cytokines, such as TNF-α, that cause inflammation. The resulting systemic inflammatory syndrome, referred to as sepsis, is a life-threatening condition which affects an estimated three million people a year worldwide, of which up to 30% will die from multiple organ failure.
Many products have been tested for their ability to treat severe sepsis and all but one has failed to-date. Xigris® (Eli Lilly) is the only product currently available which is specifically approved for this indication and there are few other products in development. However, the clinical use of Xigris® appears to be restricted by a significant risk of serious bleeding, thought to be related to its mechanism of action. We have strong evidence to suggest that CytoFab™, through the effective in vivo neutralisation of TNF-α, could become the second product to reach the market.
A phase 2b clinical trial involving 81 patients in critical care hospital units in the US revealed promising results in the treatment of severe sepsis. It was shown that patients treated with CytoFab™ had dramatically reduced TNF-α levels in their blood and lungs, required significantly less mechanical ventilation (assisted breathing) and spent less time in the critical care unit. There was also evidence of an encouraging trend towards improved survival in this small patient study.
In clinical studies of CytoFab™ in sepsis to date, there have been no adverse events that were considered definitely, possibly or probably related to treatment with CytoFab™. However, out of 110 sepsis patients who received CytoFab™, there were 7 patients who experienced events of uncertain causality that are consistent with adverse event experienced by patients receiving other ovine Fab products, including 1 episode of pruritis, 2 episodes of wheezing, and 4 episodes of rash.
In December 2005 we announced a licensing agreement with AstraZeneca for the global development and commercialisation of our anti-sepsis product CytoFab™. AstraZeneca has prepared its global development plan for CytoFab™ and has started additional phase 2 work in January 2008. AstraZeneca are conducting a 480 patient phase 2b study to confirm the dose, and will further investigate the efficacy of CytoFab™ prior to starting a major phase 3 study in the US, EU and Japan.
AstraZeneca is responsible for developing CytoFab™ as a treatment for TNF-alpha mediated diseases in man, with an initial target indication of severe sepsis. Under the terms of the agreement, AstraZeneca will undertake all clinical development work for CytoFab™ and we will be primarily responsible for bulk drug manufacturing, including the supply of clinical trial material.
The agreement has a potential total deal value, excluding royalties, of approximately £195 million to us. We received an initial payment of £16.3 million and a £7.5 million equity investment in our company by AstraZeneca, and will receive additional payments worth up to £171 million payable upon the achievement of milestones. A significant proportion of these payments are contingent on pre-approval milestones being achieved. There are no milestone payments related to sales performance. We will also receive royalties on global product sales of 20 percent of net sales which reflect the late stage development status and market potential of CytoFab™. Additional payments will also be received in return for the commercial supply of the product and will invest to expand its manufacturing capacity accordingly.
Encouraged by the phase 2b data, we believe that CytoFab™ has the potential to become a multibillion dollar blockbuster product, should it prove safe and efficacious in a larger pivotal study.