Inspire Pharmaceuticals Denufosol and Vertex 770 & 809

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.

Vertex Pharmaceuticals and Telaprevir. A protease inhibitor for Hepatitis C.

In the absence of any major news today, I decided to take a look at Vertex Pharmaceuticals VRTX.

In summary,  whilst Vertex is not a binary event biotech company, it’s near term prospects will be guided by one drug, namely Telaprevir for Hepatitis C. This drug is a protease inhibitor, which is a new class of drug that competitors are also trying to develop. Vertex has submitted a New Drug Application for Telaprevir with the FDA.

Vertex Pipeline and Timeline

	Indication	Event	Date
VX 765	Epilepsy	Ph II Top-line data	2010
VX509	Rheumatoid Arthritis	Ph II clinical data	2011
VX 809	Cystic Fibrosis	Ph II with VX 770	2011
VX 770	Cystic Fibrosis	PhIII clinical data	H1 2011
VX 222	Hepatitis C	PhII clinical data	H1 2011
Telaprevir	Hepatitis C	FDA Approval	H1 2011

source: Vertex

By far the most important event is Telaprevir. They filed an NDA in November. Telaprevir is a protease inhibitor and is likely to face future competition from Merck’s Boceprevir (which hasn’t been filed yet). Telaprevir is seen as being more convenient due to it having a shorter treatment duration (12 weeks vs. 24weeks) and also has a high efficacy in treatment of non-responders. It is also possible that Telaprevir could be used as a twice daily regimen.

Whilst Vertex could have the first mover advantage, Boehringer Ingelheim, Bristol Myers Squibb and Roche all have drugs for HCV in development and they are aiming for a once a day regimen. Moreover, Medivir recently announced excellent results in Phase II with their protease inhibitor for HCV.

The good news is that Vertex will likely be a couple of years ahead and shows superiority over its nearest rival Boceprevir. The more circumspect news is that Vertex' NDA filing is the first for this class of drug and assuming quick FDA approval may lead to disappointment. Any delay will hurt Vertex as rivals are in clinical trials. In a sense, buying Vertex would be a 'bet' upon FDA approval and expecting them to maintain a lead against the potential competition.

VX222 is being developed with the last point in mind. It is a polymerase inhibitor that is intended to be used in combination with Telaprevir. As such, it could shorten treatment time and help with efficacy with non-responders.

VX765 is interesting as it the first drug to target epilepsy via anti-inflammation, in this way seizures are believed to be able to be reduced. The upcoming Phase II data will be interesting and provide some upside potential. I would not proscribe a high chance of success with novel drugs in general.

VX770 and VX809 are being trialled in combination for cystic fibrosis. Although the phase II results for VX809 were not great, Vertex feel that-according to their laboratory research-in combination they could be efficacious in cystic fibrosis.

I did not take a position as I suspect that much depends upon Telaprevir approval. Although clearly efficacious,it is the first class of drug and I also see downside when/if Merck decide to file with Boceprevir.



Source:

Medical News Today "Telaprevir May Be Viewed More Positively By Clinicians Than Boceprevir For Hepatitis C Virus Treatment Following Their Launches In 2011"
Bloomberg "Medivir Gains as Early Study Shows Drug Kills Hepatitis C Virus"