Telaprevir/Eye on Vertex

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Telaprevir/Eye on Vertex

Vertex is collaborating with Tibotec and Mitsubishi Tanabe Pharma to develop telaprevir, an oral, small molecule inhibitor of the hepatitis C virus. The compound inhibits a unique viral serine protease (NS3/4A) that is essential for viral replication. The original patents for this compound were filed in the late 1990s, and finally, the Phase 3 clinical trial results are expected any week now, with more data accumulating through 2010.Telaprevir is a treatment for chronic Hepatitis C virus (HCV), a disease affecting 170 million people worldwide. Hepatitis C is caused by contact with infected blood or blood products. The most common risk factors are injecting drugs, (perhaps only once many years ago), having a blood transfusion before June 1992 when blood began to be screened for antibodies against HCV, and birth to an HCV infected mother. HCV can cause acute liver disease with severe symptoms, but about 75% of patients develop chronic HCV

which can vary from asymptomatic to chronic liver failure and cirrhosis over a course of 10-20 years. HCV is a enveloped, single stranded RNA virus which infects liver cells, proliferates in the cell and then goes on to infect many more cells with each replication process. The end result is destruction of the liver. The viral replication process requires the virus to make an enzyme called NS3/4A. When telaprevir is in the circulation, it binds to the NS3/4A enzyme and prevents the virus from proliferating in the liver cell.Initial trials to assess the best use of telaprevir examined the efficacy of this drug by itself in chronic HCV patients, but intuitive analysis of the data has led Vertex to find that the most impactful use of this new investigational drug is in patients with chronic HCV and a history of poor response to prior treatment with accepted drugs. Patients with previously untreated HCV are treated with a combination of pegylated

interferon alpha (which boosts the anti-viral immune response of the patient) and ribavirin (a broad spectrum anti-viral agent) for 24 or 48 weeks (depending on the type, or genotype, of HCV virus). 40-50% of the patients respond positively to this combination treatment, and achieve ‘sustained virological response’, or no detectable virus in the blood 6 months after treatment has ended. But what about the other 50-60% who do not respond? These patients have limited retreatment options and usually undergo the same combination therapy a second time, perhaps modifying the time course, with minimal chance of a successful outcome. Therefore, the development of new treatments for these patients is a significant medical need. In the already disclosed results of at least three Phase 2 trials, the retreatment of non responding patients with the standard of care combination therapy resulted in 14% of the patients achieving no detectable HCV virus in the blood

6 months after treatment ended. The addition of telaprevir to the treatment regime of pegylated interferon and ribavirin in these previously non responding patients increased the percent of patients who had no detectable virus in their blood 6 months after triple treatment ended to 53% of the patients(1). On April 15, 2010, Vertex issued a press release describing the results of a new study demonstrated that 56% of previous non responders achieved undetectable virus levels, and 97% of people who initially responded then relapsed achieved prolonged response with addition of telaprevir to the second treatment triple combination regime (2).The results of the Phase III studies are expected Q2 and Q3 2010, but it is widely expected that the positive Phase II results will predict equally positive definitive trial outcomes. Competition for treatment of HCV primarily rests with boceprevir, a compound with similar mode of action made by Schering-Plough

which was recently acquired by Merck. The development timeline for boceprevir is similar to telaprevir, but recent data seems to demonstrate that half the patients receiving Merck’s boceprevir developed anemia. The major side effect of Vertex’s telaprevir is a skin rash, which is not considered a clinically important safety issue, but can impact enrollment.The commercial potential of HCV treatment is quite large. The $2 billion market reported in 2008 is expected to expand to $7.4 billion by 2013 with the addition of the new anti-virals, most notably telaprevir. But this growth will not be sustained and will likely decrease through 2018, as the prevalence of the disease falls and the new drugs demonstrate increased effectiveness over the current treatments.Vertex Pharmaceuticals (Nasdaq: VRTX), a Cambridge Massachusetts based company, closed at $37.42 May 18, 2010. One year ago today Vertex was priced at $29 per share. Vertex’s

$7.7 billion market valuation is primarily tied to the success of telaprevir, and you can bet Wall Street will keep it’s eye on Vertex during the next months.It is quite interesting to note that the additive effects of 3 different anti-viral therapies with 3 different mechanisms of action proved to be the most effective means of defeating this virus which has a wicked propensity to mutate it’s envelope proteins to evade the immune response. This strategy mirrors the most effective strategies now being used to combat cancer. Rather than the silver bullet which was hypothesized to one day cure cancer, the greatest advances have come from using a combination of refined therapeutics, each with a specific and different mechanism of action against the cancer cell: a one-two punch combined with the jab to knock the opponent flat on the mat.1. McHutchison, J.G., Manns, M.P., Muir, A.J. et al. Telaprevir for previously treated chronic HCV

infection. New Engl J Med. 362: 1292-1303. 2010.2. http://investors.vrtx.com/releasedetail.cfm?releaseid=460333

http://Hepatitis Cnewdrugs.blogspot.com/2010/05/telaprevireye-on-vertex.html