any metric or market model is based on assumptions, correlations obtained from historical data do not necessarily indicate causality, hence i am reluctant to base my investment decisions on these tools. I rather follow my own scientific reasoning and comment sense, sometimes it works great, sometimes I am totally wrong - that's life.
two weeks ago I guessed the bottom to be around $70, (so I avereged up quite a bit), now I hope that $60 might be the bottom, but that's pure speculation (hope?), still don't think that the decline in sp is due to VRTX related reasons, the street just doesn't like biotech right now, the moment VRTX releases positive data on CF trials we will see a dramatic rise in VRTX sp
(at least I do hope so ;-))
the British Medical Journal has a very negative assessment on Tamiflu:
"Important benefits have been overestimated and harms under-reported. In particular, the review found no compelling evidence to support claims that oseltamivir reduces the risk of complications of influenza, such as pneumonia and hospital admission, claims that were used to justify international stockpiling of the drug."
will this increase chances for VX-787?
wodner why there has not been a pr yet on Ivacaftor expanded label approval for use in non-551 CF patients. PDUFA decision was scheduled for March 27 for use in non 551 gating mutations patients
VX-765 has an interesting history. Originally had been developed as a fast follow-on for VX-740 (pralnacasan) in RA. But no corporate partner was found, so VX-765 was shelved. Then in 2009 Italian scientist at the university of Verona identified efficacy in preclinical models in epilepsy. In collaboration with the Italians Vertex performed clinical studies in epilepsy. As it look likes results were not good enough to warrant registration trials, so once again VX-765 was shelved. Now that Warner Greene's group has identified activity of VX-765 in HIV it will be interesting to see whether Vertex will conduct clinical trials with VX-765 in HIV, which, if positive, might result in a market potential that might dwarf the CF franchise.
i agree with third and qd that the Vertex CF franchise is more than just "hope". So the present low 70s may well be the last chance to get into VRTX before it enters into substantially higher territories.
But if you can't stay the heat, better stay out of the kitchen.
Sentiment: Strong Buy
Adam Feuerstein @adamfeuerstein
. @MarkSchoenebaum Are you surprised by the level of $VRTX hate?
Mark Schoenebaum @MarkSchoenebaum
@adamfeuerstein I am not sure it's really hate. It's just viewrd as a very binary event. Vast majority of investors simply avoid those.
according to the Drug Analyst Consensus Database VRTX will have theses sales:
Drug Name Indication 2012 2013 2014 2015 2016 2017 2018 2019
Incivo ......HCV .............1,162 466 ......Subsc 15 .........13............9 ............12..... .-
Kalydeco CF ..............172 ........371 ......Subsc 1,066 1,868 2,624 3,151 3,749
Kalydeco & VX-809 CF - - ..............Subsc 390 .........975 1,558 2,253 3,276
so the CF franchise will amount to about 7 bn annually within a few years,
now just guess the adequate share price ;-) Less
the DrugAnalyst Consensus Database has interestimg forecasts of VRTX revenues, detailing each product separately
can't post the link, so just google Drug Analyst Consensus Database
this book really is worth reading for all that are interested in insights on Vertex! fascinating facts on the discovery of cf compounds and lots more.
Ian F. Smith - Chief Financial Officer and Executive Vice President
And Robyn, on types of transactions or collaborations that we're looking for, clearly, our focus right now is on what the VX-509 and VX 787, 787 being the molecule for, potentially, to help with flu. So we'll continue to have discussions. In particular, we've just recently received the 24-week data for VX-509, that allows us to continue those discussions. And as those progress through this year, we'll advise you appropriately.
Adam Feuerstein@adamfeuerstein$VRTX no swagger, no cockiness from these guys. The magnitude of the importance of Traffic/Transport weighs heavy. #JPM14
It should be noted that while several rounds of analogue synthesis and testing were required to go from the hit VRT-532 to drug VX-770, compounds were strictly assessed for an effect on ion transport in mutant CFTR- expressing cells, rather than CFTR binding or other assays of isolated CFTR protein. While ivacaftor is unable to restore normal CFTR function to cells with the ΔF508 mutant CFTR, due to its dual defects in trafficking and gat- ing, it restores normal CFTR function in cells with G551D, as this mutation only affects gating.107 For this reason, iva- caftor was moved into clinical trials for the treatment of patients with cystic fibrosis with the G551D mutation and found to improve not only sweat chloride measurements, reflecting the improvement in CFTR function, but also lung function and nutritional status, both important clinical parameters, leading to its approval for the treatment of patients 6 years and older with this mutation in January 2012.103
This would represent a triumph for target-based drug discovery had ivacaftor been developed with the CFTR as a target, based on structural studies of the CFTR protein— developing a precise molecular mechanism of action to repair the defects in the mutant channel. Instead, ivacaftor represents the development of a genotype-specific person- alized therapeutic using phenotypic drug discovery meth- ods and, as such, provides a counterexample to the widely held assertion that personalized medicine is only possible using the target-based drug discovery approach. Indeed, the exact mechanism by which ivacaftor exerts its beneficial effects on CFTR gating is still unclear, and although recent work suggests direct action on CFTR itself,108 this was not by design. Phenotypic drug discovery can yield targeted, personalized therapeutics.
copied from "Clinical Relevance of Target Identity and Biology: Implications for Drug Discovery and Development" J Biomol Screen 2013 18: 1164
Recent advances in the treatment of cystic fibrosis provide an example of how personalized medicine can occur with- out knowing the precise target of a novel therapeutic and can be applied with limited provider understanding of the biology at work. Cystic fibrosis is a fatal genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a mul- tifunctional protein whose primary role is as an adenosine triphosphate (ATP)–gated chloride channel essential for normal salt and fluid transport in multiple organs, including the lung.102 The discovery of the CFTR gene in 1989 prompted the development of therapeutic approaches to restore normal CFTR function, either through replacement of CFTR through gene therapy or by improving the function of the mutant CFTR.103 The latter is complicated by the fact that different mutations predictably affect the CFTR protein and its function in different ways.102,104,105 While the most common CFTR mutation, ΔF508, results in both impaired trafficking to the cell surface and problems with channel gating, other less common mutations, such as G551D, affect only channel gating.104–106
Using cells expressing mutant CFTR genes, Van Goor and colleagues106 at Vertex Pharmaceuticals screened 228,000 compounds for compounds that would enhance CFTR function using a cell-based fluorescence membrane potential assay. Specifically, they screened for two types of compounds: CFTR correctors, which improve ΔF508 CFTR trafficking, and CFTR potentiators, which improve ΔF508 CFTR gating at the cell surface. From the CFTR potentiator screen, hit selection and lead optimization yielded ivacaftor (VX-770).
" I think a key study deliverable would be determining what that upper limit is."
you are right, two important data to be determined in clinical trials are NOEL (no effect level) and MTD (maximal tolerated dose). So in principle it is not negative to have a dose that is above MTD (i.e 400 mg for VX 135), the development consequently has to focus on 100 mg and 200 mg.
Almost one year of Kalydeco
Decided it was time for a summary post about my new health on Kalydeco.
I have been on Kalydeco for 11 months through the Named Patient Program, a program where Vertex supply Kalydeco to those who are very unwell. Kalydeco is the first medication that treats the underlying cause of Cystic Fibrosis in patients with the G551D mutation.
Before Kalydeco my lung function was 41% and very unstable. I was in hospital every 3-4 months. I was on medications that treated the CF symptoms; these were becoming less effective as I grew older.
For the last 11 months my FEV1 has been stable at approx 70%. This is amazingly stable compared to before; for 20 years my lung function has varied up to 20% from month to
month, now I am stable for the first time in my life. This is my highest in 3 years.
I have stayed out of hospital for 11 months, which is a 20 year record (I am currently on IVs for mostly prophylactic reasons, I will post about this soon). Before Kalydeco I had over 60 hospital admissions, equalling 3 years of my life.
Every aspect of my health has improved with Kalydeco, I have gained 6kg, I can run up stairs, I can sleep without coughing and I’m attending uni more often. My sweat test results have improved from 102 to 40. This is much lower than the point (60) associated with the CF diagnosis.
Previously I did not plan further ahead than 5 years. At the age of 28, with a life expectancy of 37, I knew transplant was edging closer. Thanks to Kalydeco I now don’t have to plan around hospital and CF, instead I can plan to have a family, a career and to grow old with my lungs.
here is how Vanda got fanapt approved.
The strategy has worked for Vanda in the past. After FDA rejected the schizophrenia drug Fanapt, Vanda "engaged" a regulatory consultant -- also never identified -- to assist the company in convincing the agency to change its mind. The FDA ultimately approved Fanapt and for his efforts, the regulatory consultant was paid a "success fee" totaling $6 million, according to Vanda's SEC filings.