This kind of report is aimed at influencing the stockmarket, not at reporting success or failure of a particular therapy.
As a Phase I trial, its stated goal is to determine if the treatment is harmful, not if it is beneficial, and to test if the dose range potentially affects whatever they are measuring [1].
Thus, the title of this post is misleading, there was no test to determine the effect of aducanumab on Alzheimer's disease.
Biogen's stock will go up nevertheless... apparently it has by over 9% [2]. There is such a large gap between basic understanding of science and biology and those who make markets....
Actually, they DID collect clinical response data even though it was a Phase Ib trial. Specifically, as the NYT piece mentions, they measured both cognitive function (via the mini-mental state exam aka MMSE and the clinical dementia rating scale aka CDR) and plaque removal (using one of Lilly's imaging agent) in relation to dosage. The data shows consistently improving cognitive function and plaque removal as dosage increases (albeit at the cost of additional side effects).
Now this is certainly atypical for Phase 1b data but it does (to some extent) justify Biogen increasing in almost $10B in market cap. In fact, the Phase 1b data is compelling enough that Biogen is going straight to Phase III trials.
While it is healthy to be skeptical about early trial results and subsequent market movement, I think it's clearly misplaced here.
I see where you're coming from, but I'm going to have to disagree somewhat...
This kind of report is aimed at influencing the stockmarket, not at reporting success or failure of a particular therapy.
It's both. A company is required/expected to publicly release material information that could influence the stock price. The clinical data also supports whether or not the molecule "passed" this phase of study.
there was no test to determine the effect of aducanumab on Alzheimer's disease.
There is no reason why you can't have efficacy endpoints in your phase 1 study. The endpoints tested in this study are indicators of progression of Alzheimer's disease.
That said (and others here have pointed it out), this is a VERY small study. There have been numerous other examples of Alzheimer's therapy that have show promise in early trials and so far, they have all turned out to be duds. I hope that's not the case here.
Lack of statistical power. Phase I enrol too few subjects for efficacy. The reason they do a Phase I is to determine it would be safe to do a larger trial.
Source: I used to work for the company that is most likely to have done any MRI analysis for this study. We did Phase I/II/III and they are very different beasts.
The point of statistical tests is to assess the accuracy of a prediction. These trials were not designed to predict/test the efficacy of the drug, therefore no conclusion regarding efficacy can be drawn.
It is of course possible that there was a real effect, and that this is reflected in the data gathered, however to determine if that is the case another trial has to be performed.
I'm pretty sure if they add efficacy endpoints to Phase I, it becomes a Phase I/Phase II and the efficacy is for Phase II. The other problem with efficacy in Phase I is that alzheimer's efficacy is not measured over such short time frames.
IMO what you said might mislead inexperienced people about a Phase I trial. It's entirely true, but people might not realise there are usually some previous experiments (e.g. in animal models) suggesting that the drug will be efficacious.
These "drug X may help Y" are always misleading, usually by the media.
Quote:
The most common side-effect was a type of brain swelling. It seemed to pass once a patient's dose was lowered, Biogen said, but it's a worrying symptom, and was worst in patients given the highest dose. Inflammation of the brain has caused companies to dump some earlier experimental Alzheimer's treatments.
But I want to comment on that. The article makes it seem like mutual fund managers provide no benefit whatsoever because they did not beat the market.
Bullshit. They might not help investors make money, but they still provide benefits. Saying otherwise like saying Apple and Google and Microsoft provide no benefit because they have not done any better than the tech sector as a whole. In fact, we can look at the growth of the market as a measure of how well mutual fund managers are investing.
We need to remember, mutual fund managers compete with other mutual fund managers. They're investments do matter as they dictate where investment money in our economy goes. They might not make money relative to the market as a whole, but they still provide important benefits to society.
For example, just because airlines only make .2% profits, their services benefit society tremendously.
Replacing mutual fund managers with investing in any company whatsoever (though limiting to public companies changes things) by "flipping a coin" like the article suggests, would likely have a very bad impact on the economy. It would have no effect on how well mutual fund managers do relative to the market, though.
The more fund managers you have, the more efficient capital allocation you'll have. The fact that mutual fund managers do not beat the market means that we have too many fund managers chasing diminishing returns. The increased efficiency in the markets is too small for their wages.
As the fraction of active fund managers to passive fund managers decreases, this fact will change. More and more passive investors following in the footsteps of less and less active investors. This means the tracking error will increase. At some point the cost of the tracking error will be about the same as the cost of active management, and that is when we have the right amount of active management.
Other monoclonal antibody therapies have had similar side effects. There is the possibility that this is a direct reaction to the removal of the plaques. Also, I wouldn't get my hopes up until there is a lot more data. See what happened with Elan's bapineuzumab.
"The drug, called aducanumab, appears to have met or exceeded Wall Street expectations in terms of how much the highest dose slowed cognitive decline. However, there was a high incidence of a particular side effect that might make it difficult to use the highest dose."
There is so much that scares me about this statement.
It's got a ways to go for sure, but the exciting thing is this is the first drug ever to make it this far, with statistically significant reduction of plaques and cognitive decline.
This isn't the first antibody therapy that tries to reduce plaques (Bapineuzumab, solanezumab, gantenerumab, crenezumab, etc.), but is it the first one to "work" correctly, but still fail? I don't believe so. I think bapineuzumab also showed early promise at reducing plaques, though I don't remember if they did a cognitive analysis that Biogen did here.
Don't get me wrong. I think this is the most promising one we've had, if for no other reason than the method used to develop it. They took people who lived into old age without Alzheimer's, and found antibodies from them that targeted Abeta (so they claim). Really cool stuff, if true, and very promising.
It works on amyloid beta. Curious how this drug compares to magnesium supplements since there's been research showing that magnesium also effects the amount of amyloid beta.
As a Phase I trial, its stated goal is to determine if the treatment is harmful, not if it is beneficial, and to test if the dose range potentially affects whatever they are measuring [1].
Thus, the title of this post is misleading, there was no test to determine the effect of aducanumab on Alzheimer's disease.
Biogen's stock will go up nevertheless... apparently it has by over 9% [2]. There is such a large gap between basic understanding of science and biology and those who make markets....
[1]https://en.wikipedia.org/wiki/Phases_of_clinical_research
[2] https://uk.finance.yahoo.com/q?s=BIIB