Biogen reverses decision to not pursue FDA approval!

Do we all have new hope for help from big pharma now?

Drugmaker reverses course, plans to seek FDA approval for Alzheimer's treatment flip.it/vl1mmR

[WinnieThePoo]

Good news on a few fronts. First, I recently bought Biogen shares for my pension fund. 2nd, it (maybe) un-debunks the beta amyloid write off, and that was being used to question the alpha synuclein pd hypothesis. And 3rd Biogen pull trials where results indicate no success.

[park_bear]

I found this well-informed analysis of the Biogen situation:

arstechnica.com/science/201...

by Diome

"A bit of background: the key question we all have is whether aducanumab provides any functional benefit, so what does ‘functional’ mean in the context of Alzheimer’s treatment?

Generally, these studies measure functional outcomes using a battery of tests designed to quantify cognitive impairment. These tests look like variations on the common memory games you are familiar with (you can see examples at alz.org/professionals/healt ... assessment), e.g. picking matching tiles to test short term recall, clicking a button when it lights up to test reaction time, being told the time and asked to draw a corresponding clock-face for abstract reasoning.

In order to be included int the study, the participants had to undergo a baseline assessment that determined their level of cognitive impairment, and then undergo the same assessment at specific intervals (1-6 months, determined by the study protocol) to measure change.

So, given that, we can draw a couple of conclusions about real-world implications of this latest news from Biogen.

First, given the initial failure in March, any real-world functional benefit that turned up after is likely to be very small. The ‘significant’ results were for people who already had significant cognitive impairment to begin with - e.g. had major problems with reaction time (likely couldn’t drive) and short-term memory recall (difficulty remembering they turned the stove off after cooking, for example).

Aducanumab was only shown to *slow the rate of decline*, not any improvement in cognitive function. E.g. the participants who showed any measurable difference only got worse at a slower rate than the control.

Improvement in outcomes likely means a small slowing of the rate of decline in the cohort, but very little meaningful change at the individual level. Maybe 200ms difference’ in reaction time, and matching 1-2 more card pairs in a set of 50, E.g. if you met any of the participants who had received aducanumab, you wouldn’t likely be able to tell they had received treatment, because they already had trouble functioning, and got worse even if they were on the drug.

Second, because the functional impairments were measured using pen-and-paper tests, there is a high probability that any improvement is noise due to subjective scoring of the raters.

The Phase III aducanumab trial primary outcomes were determined using primarily pen-and-paper assessments given by a trained ‘rater’. Secondary outcomes (e.g. interesting but less determinative results) were determined using assessments conducted with specially designed software. For the primary outcomes, raters typically get trained on how to conduct the assessment (specific script questions) and how to score the results.

The error rates from the pen-and-paper tests are pretty high (like 50% variability in scoring across raters). Because each participant will have a different rater at each cognitive assessment, much of the variation is due to scoring errors/differences. The data analysis protocol will try to deal with this using statistical techniques, but because the sample size is still relatively small, a lot of these results will fall out with the more rigorous analysis from the FDA.

Finally, its worth noting where this fits within the overall Alzheimer’s research field; aducanumab is not a success. Slowing the rate of cognitive decline in significantly impaired participants does not likely translate into any real quality of life improvements. The real potential for aducanumab was to prevent cognitive impairment from progressing in early Alzheimer’s patients, or ideally in the ‘prodromal’ group (where there were biomarkers of amyloid plaques and mild cognitive impairment, but no clinical diagnoses of Alzheimer’s). Since that data was unequivocal (aducanumab did nothing for those groups), it is highly unlikely that these new results are indicative of a long-term treatment option for folks with Alzheimer’s."

[Emphases added]