As everyone familiar with Affinitac knows, the basis for the phase III trial was the results of the Phase II trials in advanced NSCLC ie 46% response rate and median survival of 15.9 months. The primary endpoint of phase II studies is response rate and not survival, because lung cancer survival is very dependent on patient selection. Although survival is the most important issue in phase III trials, response rate is more important in phase II due to lack of a control arm and randomization. Let's concentrate on response rate,ie is 46% response rate unheard of with carb/taxol alone without Affinitac? NO, As a matter of fact, there are many studies published in the literature with comparable and even better response rates with this combination:(up to 62% response rates have been reported)
All these studies have 50+% response rates. Why? Becasue of patient selection and small number of patients overall, just like the original affinitac study. None of these numbers are ever nearly reproduced in large randomized phase III trials. But what really gives away the affinitac response rate of 46% as unreproducible in a large randomized study is that in the next trial with gem/cis which was roprted this year the response rate dropped to 37%, even though some believe that this combination is a stronger one than carbo/tax. And they have not (conveniently) reported the median survival on that one but I bet you it is nowhere near 15.9 months.
Although survival is not as important in phase II studies, there are small studies with carbo/taxol and gemcitabine and carbo that have comparable survival rates and much better than what isis would have you believe, ie 8 months:
0741276&dopt=Abstract (16 month median survival).
Again, the lack of reproducibility in the gem/cis trial is a confirmation that the survival results and response rates in the carbo/tax trial were a fluke based on patient selection and small sample and will not be reproduced, and therefore the trial will fail to show a statistically significant improvement in survival.
Novartis was smart and got out of isis-3521 back in 1999 as the early trials of this agent showed very little antitumor activity on its own.
By the way, for those of you who don't know me I am a radiation oncologist. I have not treated or heard of any patients treated on the trial. All of the above is my own independent analysis/speculation. I have been bearish on isis-3521 for a while and not becasuse of the recent rumors.
Your input here on this board has saved numerous investors from being wiped out.
Those investors, who could not distinguish between the common sense of your posts, and the pumpers have no one to blame but themselves. (fergie, I still love you anyway)
It is shocking that highly paid fund managers did not take advantage of your advice. They get paid and you didn't. Seems the duped like to be duped. Strange world.
Note: I fully disclosed my sale at $7.2 a few months ago and even thought I think the stock is oversold at these levels I have not bought back in yet. I hope to buy after the data are released but I will wait to see what the results look like and how the price reacts.
Long term, I think the stock is a steal here or at lower levels. If the trials are not a total bust (some improvement) and LLY stays with ISIS, they may even buy ISIS if the shareholders push hard enough. It is all speculation until we see the results.
Radiation guy's inputs and your as well, are just speculation on the sell side
All his , I got to admit, nice sell side presentations, are just speculations, he possible has no clue but what he read, but there is a lot of pro documentaion on antisense field that he conveniently did not quote !
Whenever a revolution is underway there are many skeptics on the fences shouting it is not possible, that is exactly why things still happen
Listen to this story:
OnCe upon a time , in the leap frog village, someone came with the idea of a contest to determine the frog who can climB on the top of the highEST tree around. They chose the tree and all the contestants begun climbing . Down the tree were the frog spectators saying "Look how tall the tree is , it is impossibe to climN on the top !
One by one, the frogs were droppping off the contest and yet again some of the frogs were yelling "it is impossible, they do not have the force, it is really too high"
More frog contestants were falling down the earth but finally ONLY ONE frog made it to the top of the tree.
When the frog came back everybody was shouting " How did you do it ? How come you are so strong and not affraid ???":
Than they figured it out that the winner was DEAF
Now figure this out yourself !
I can't believe the longs have allowed this to tank so much. I should have stayed short:
I am sure that isis will report all kinds of subgroup analyses to get some sort of positive result that it can report, just like the street.com reporter mentioned.
But the study will not meet its primary endpoint, no way.
Waiting for a last minute dead cat bounce to 5 before going short.
Note "waiting for...5 to go short". Now even the strongest bulls will accept that the price won't go over 5 before the trial results are in. So he can have it 2 ways:
1. If the trial fails, he can say "I told you so
2. If the trial succeeds, he can say "I never shorted, see my post"
So he can continue his deception with the same arguments made in a previous post (copied and pasted here)
<<Naughty messenger, I challenge you to find a link that will provide evidence that I shorted avii under 5.
Please provide evidence if you can, anyone. The dates of those messages are clear. >>
in response to this post:
This way he can keep posting his deceptions and bash a few more biotechs, without having his "track record" blemished. Who says hedgefund bashers can't be creative?
objective responses and survival.
I will agree with you that such a thing is correlated but I noticed that all your examples are cytotoxic chemo. In those the mechanism is immediate shrinkage (if it works) or none (if it doesn't). Which is why the notion of OR has taken hold.
I think the mechanisms could be different enough for the regulatory pathway modifying biologicals that such a strong correlation between OR and survival is neither ruled in nor out.
Your on Top of the Mark.
As you, I, others, have stated the trial has to fit the patient and the trial has to be patient driven - not product driven; if the trial is going to be "effective" and provide, competitive advantage, shareholder value.
The work that needs to be done is a integrated, cross-functional, network of reputable physician-investigators with R&D sponsors needs to be built. Each specialty should have open access to the trial data base.
When a patient needs treament and the patient has been deemed a "fit" for the trial the physician can enter the patients name into the web-based data base and the physician with the help of the web-based data base will contact the pharmaceutical company to enroll the patient in the trial. Thus, meeting the needs of the patient and the needs of the trial.
In my mind, limited access trials that are looking for Proof-of-concept/Scientific hypotheses and the ones that are not open trials are time consuming and lack cost efficiencies. Limited access trials in-my-book will soon be a thing of the past.
Pharmacogenomics, patient information management systems will also deliver significant market returns within the next 10+ years. The key(?) The new executive must integrate both business development and pharmaceutical/biotech development into strategic business models.
Well, I might be doing some wishful thinking on 16 myself - I agree that C is more likely. However, A is the correct thing to do, and would restore a lot of sanity to the markets. Dividends need to be reinstated as a method to distribute earnings to shareholders, and at present, there is a disincentive to do so.
But C probably will be correct. I usually don't win these things, so I wouldn't take any of this seriously - I certainly don't plan on changing any of my investments on the basis of any of my opinions. Now, if you understand that last comment, you are on your way to being a seasoned investor.
OK, I was out, and picked up a Barron's. Here's my list, and then I'll look at yours and the editor's:
13. Intel (INTC)
14. EK (Kodak)
OK, so I did look at the editor's pick on #18, which is something I know little to nothing about, and coffee sounded as good as anything.
You are kidding me that you think INTC will be the worst-performing stock on the Dow. I almost picked GE, and probably should have, but INTC has the most upside potential over the next year, in my opinion, of any Dow stock. This is because AMD is struggling mightily with manufacturing (TMTA is a non-factor, sorry to say), and INTC often is able to stick its pricing in this kind of environment. We'll see - thanks for mentioning it!
+++It is going to be exceedingly difficult for the FDA to police the new age of individualized medicine.
For the next 5-8 years, the big $ will still be in small molecules and mABs. +++
I have a great deal of trouble visualizing the economics, much less the regulatory path, for "individualized medicine". It's a great concept, but I doubt that we will see it in full bloom in the next 20-30 years. Hey, I remember when the news-magazines discussed plans to build factories in orbit to take advantage of no-grav conditions 8-).
I think that you are correct - Mabs are no longer bleeding edge, so some real $ could actually start accruing to the leaders in the field. But I think you are selling antisense short. There are indications out there where it will be the most effective approach. You should look at the work AVI has done with dwonregulating cytochrome P450, and the recent penguin(!) anti-viral news.
Too many to list, here are a few examples: