Some interesting news flow today related to the failure in Phase III of Inspire Pharmaceuticals cystic fibrosis drug denufosol tetrasodium. I'm particularly interested in how this might relate to the probability of success of Vertex 770 and 809 which are both due to report on Phase II trials in 2011. I'm a great believer that probabilities of success for drugs in FDA clinical trials need to be looked it in the context of a variety of factors other than just plucking an industry standard number out of the air. Why biotech analysts insist on pencilling in 50% for almost every phase III trial, is a mystery to me. I think one of the key factors is the class of drug, hence my concern for Vertex.
I've previously written about Vertex's pipeline here and also featured one of their drugs in an article about Rheumatoid Arthritis here. On balance, I think the Inspire news is a net positive for Vertex. It will remove a competitor who could have grabbed market share with a drug that works in a similar way in targeting the underlying cause. However, I think the mode of action is sufficiently different to not effect Vertex and the probability of success of 770 and 809.
New Drugs in Development for Cystic Fibrosis
Incidentally, Gilead Sciences had Cayston approved in 2010 for cystic fibrosis but it is an inhaled antibiotic therapy which acts on the pseudomanal infection in order to provide an increase in forced expiratory volume (FEV). Discovery Laboratories has recently reported good results with lucinactant in Phase IIa, but again this is drug targets mucus airway adhesion. In contrast, Inspire and Vertex's drugs target the underlying cause.
In Cystic Fibrosis (CF) the basic problem is that the epithelial cells have a defect, which is caused by the production of faulty Cystic Fibrosis Transmembrane Regulator (CFTR). This defective CFTR causes poor ion flow across membranes. The result being that chloride outflow is restricted and sodium inflows are unrestrained. Eventually, this build up causes the heavy mucus that creates lung infections and damage. As noted above the Gilead Sciences and Discovery Labs act on the mucus build.
Inspire Pharmaceuticals Denufosol and Vertex 770 and 809
This drug acts on the underlying cause by trying to activate an alternative chloride pathway that is believed to be in the epithelial cells. Essentially, denufosol is a synthetically created version of uridine triphosphate (UTP) which is believed to be able to trigger the appropriate receptors in the epithelial cells, in order to create this alternate chloride pathway and clear the mucus.
However, Vertex 770 is different to denufosol in that it acts as on the CFTR protein itself. It is a CFTR potentiator which is aimed at increasing the function and efficacy of the CFTR proteins in ion transfer. Increasing chloride flow such action will obviously reduce mucus build up. Moreover, what makes Vertex 770 attractive is that it can also be used for cystic fibrosis in other organs such as the pancreas.
Conclusion on Vertex 770 & 809 Chance of Success
I don't think it is fair to reduce Vertex chances with 770/809 because of the denufosol failure. The denufosol results were surprising, as they had a very strong Phase II and more analysis needs to be made. However, if anything, I think it is a net positive for Vertex. A competitor drug has been taken out of the immediate running.
Vertex has 770 in Phase III for G551D Mutation. They could submit by year end 2011. This is shaping up to be an exciting year for Vertex.