An abstract from Science News This Week (Dec. 13).
[[ Jon Cohen
A new, remarkably powerful drug that cripples the hepatitis C virus (HCV) came to market last week, but it sells for $1000 per pill. The drug, sofosbuvir, must be combined with other drugs and used for 12 weeks to cure an infection, a regimen that only wealthy countries can afford. Advocates are urging Gilead Sciences, sofosbuvir's manufacturer, to sell the drug at a steep discount to cash-strapped countries, which are home to more than 100 million HCV-infected people. And they want Gilead to offer this differential pricing today, not several years from now, as happened with the anti-HIV drugs that revolutionized AIDS treatment.]]
if not before year end, then soon after....R117H is close to completion. They should also have 135/dataclasivir soon....
I was under the assumption that there will be more clinical data being released for the gating mutation R117H before the end of 2013. Is this true? Do you know if the study has been delayed for any cause?
Thanks for the feedback. Given the importance of the CF franchise I hope the delay is not due to bad data or difficult to interpret data .. I think that patients with this mutation have lesser functional deficits and therefore may be more challenging to get a response with statistical significance, ???
"Doctors report success with gene therapy, a big win against leukemia and other blood cancers" ~ Novartis
I always have questioned SVR 12 or SVR 24 has land mark for Hep C cure. I think more important is if the therapy prevents Hepatocellular cancer. I know some folks says that if u prevent fibrosis, u prevent cancer but new micro RNA targets are telling me another story. MD Anderson is sponsoring this study and is recruiting. TVR may will come back.
Also work being done by PFE...
"A CTD–Pfizer collaboration: manual curation of 88 000 scientific articles text mined for drug–disease and drug–phenotype interactions"
What happens when this becomes the industry norm?
Google the following articles:
"Computational Chemists Awarded the Nobel Prize By the Royal Swedish Academy of Sciences"
"A self-updating road map of The Cancer Genome Atlas"
"DNA scientists map origins of cancer"
"Cancer’s family tree mapped by fingerprinting single cancer cells"
"Computing Model Could Lead to Quicker Advancements in Medical Research"
~ Add to that work being done by The Cancer Genome Atlas, AMIA, and a few advanced genomic companies and even work being done by GE.
So I think the rate of change is going to be faster than expected once all the dots are connected, which I think will happen in about 3 to 5 years.
Here's the opinion of a biotech analyst, Andrew Fein, earlier this year on the 809/770 studies and the prospect for approval based on primary endpoints (FEV-1) and secondary endpoints.
'As forVertex, as we get closer to the 2014 data readout in the company's ongoing combination study of ivacaftor + VX-809 in cystic fibrosis (CF), investors will start to realize that Vertex's study is extraordinarily overpowered and that the product's probability of success is really high. Given that this will be the first corrector-potentiator combination available in the cystic fibrosis market, Vertex is going to define its own level of clinical significance.
What I do expect, though, is increased focus on the secondary endpoints (such as weight gain) as we get closer to the time of data readout. This could prove fodder for shorts, as we have not seen enough data to support secondary endpoint improvements. Nonetheless, it will simply be noise, as a statistically significant improvement in the study's primary endpoint (relative improvement in lung function; forced expiratory volume in one second [FEV1]) ought to lead to approval.
TLSR: What is overpowered about the Vertex study?
AF: Vertex is a rock star within the cystic fibrosis patient community. A simple perusing of the various cystic fibrosis patient blogs readily drives home this point. The VX-809 phase 3 studies are powered at 90% to detect a 5% difference in relative FEV1 improvement. Given that just about every cystic fibrosis patient wants to be involved with its state-of-the-art clinical study, the company is able to enroll the ideal patients, those with forced expiratory volume predicted in the range of 40–90%. Patients in that range at baseline are best suited to demonstrate small changes in lung capacity. The company's positive perception within the CF community should also yield "flash" over-enrollment in the study, shortening the study's timeline and padding its statistical buffer.
Does the recent focus on secondary end points cause you any concern that even though still blinded vertex thinks fev improvement won't be good? Would they have any idea on whether fev is improving based on overall results?
Even if it does, mutations can occur only in few cells out of trillion body cells in a CF person. For this reason, I am confident that the two Ph III trials of 809/770 will show strong efficacy and would be more than replicate the efficacies of the two highest doses given to Cohort 2 and Cohort 3 of Phase II. Besides, because the drug action mechanisms of VX-809 and VX-661 are the same, good results of VX-661 not only support the results of VX-809 and vice versa, but also strengthen the validity and statistics (p-value) when the two data sets are combined.
Vertex’ fundamentals will easily surpass Alexion’s next year.
Company’s fundamentals and its perception by market participants should determine its share price. However, quite often the share price can determine the perception of the company to project distorted sentiment. I chose two similar biotech companies to contrast the differences.
Even if Van Goor had never invented VX-809, VX-661, and second generation correctors, Vertex could be profitable with Kalydeco alone with annual revenue and earnings similar to those of Alexion Pharma (= $1.4 B and $1.7/share, respectively, provided Vertex downsizes to the Alexion workforce of 1300 employees). The market cap of ALXN is 24.6 B as of last Friday. Alexion has only one drug Soliris for two rare indications, PNH and aHUS. Soliris is humanized mAb(=monoclonal antibody) to target C5 of complement system. It enjoys monopoly in treating the two indications now, but may face a serious challenge from Alnylam’s ALN-CC5. ALN-CC5sc is subcutaneously deliverable RNA drug and has the advantage over a mAb. Alexion is however developing other mAbs in phase I and II trials.
On the other hand, Vertex is conducting two VX-809/770 Phase III trials and Phase II trials that include a VX-661/770 trial. Both of these two combos have tremendous market potentials.
Several weeks ago at the NACF Conference 2013, it was reported that a long term use of Kalydeco was efficacious and safe. Kalydeco on G551D patients were shown to be effective and have NO tachyphylaxis (=drug fatigue) over a period of 144 weeks. There are molecular level reasons for this. Drugs targeting cancer cells, or virus, bacteria encounter tachyphylaxis after a short or long-term use. This is because genome in cancer cells, viruses, and bacteria are fundamentally unstable and target segment of genome can mutate. On the other hand, CFTR gene is stable and its mutation is rare events as we know, and the chance that target gene segment will mutate again during a lifetime of patients will be extremely unlikely. [contin']
It is going to take a long time before human race is freed from this most dreaded disease. But one day in a distant future an oral tablet combo may be able to turn off the arsenal that cancer cells employ (BMY's drugs have to be injected and have severe side effects). Positive effects of such drugs is that people will live happier and more productive lives.
Many big pharmas and biotechs are developing cancer drugs and the competition among them will keep the cost down, and at the same time keep societal burden to the minimum.
Agree with everything you have said. With the current developments in both mapping (reference last 7 days) and immuno-therapies (too numerous to mention), cancer will be, or at least most forms of it, will be easily treatable in 5 years.
I am curious your thoughts on the implications on the structural changes in the healthcare system / economy that causes... because current therapies and treatment centers eat up a lot of money... translate economic potential. I think there is going to be a whip lash effect.
Whose oncology are you referring to? Both BMY and VRTX are pursuing cancer drugs right now. The future is in immuno-oncology. Right now, monoclonal antibodies are used in targeting toxins to cancer cells (SGEN, IMGN) or in blocking evasive ploy cancer cells use (BMY's Yervoy and PD-1 inhibitor). I speculate that Vertex is working on a small molecule blocker of immune evasion deployed by cancer cells. If this is true, it will be revolutionary. They are going to talk about new drug candidates in the new year.