New Alzheimer’s Drug Shows Big Promise in Early Trial Results

[Fc1345linville]

This article appears in today's NYTimes, on the front page, no less. It does sound promising but too early to celebrate.

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https://www.nytimes.com/2018/07/25/heal ... v=top-news

[Chai]

This is BAN2401 Phase 2... It should be noted that E4 carriers were moved out of the high-dose arms of the trial due to higher risks of brain swelling. 71% percent of placebo patients were E4 carriers, versus 30% of those given the highest dose. "The fact that there were fewer people predisposed to worsening faster may have been responsible for the benefit, not the potency of the treatment, some analysts said..." https://www.bloomberg.com/news/articles ... 0-in-study

... a decision by European regulators to move APOe4 carriers out of the high dose arm as they were worried by the threat of brain swelling — or ARIA-E — which they are prone to. APOe4 carriers are at higher risk of the disease as well as faster progression, and putting them in lower dose arms — while leaving APOe4 patients in the placebo group — raised the possibility that the researchers had made it possible for the high dose arm to hit statistical significance.
https://endpts.com/eisai-biogen-outline ... g-ban2401/

The disparity between the 30% rate of APOe4 carriers in the highest 10mg/kg Q2 week arm, and the 71% rate in the placebo arm, and the 73-91% rate of APOe4 carriers in the other active arms, provides a putative explanation for the difference in cognition decline seen in the highest dose arm compared to placebo and other active arms. If Eisai’s sub group analysis suggests that this difference in decline persists even in the patients in all the arms who are not APOe4 carriers, this program may have a future, but if not, it could easily turn out to be an interesting artefact in the ongoing beta amyloid Alzheimer’s disease saga.
https://endpts.com/eisai-biogen-outline ... g-ban2401/

[Orangeblossom]

Yes this has also been mention this week in the UK papers as well.

Wonder if it may be used preventatively? Looks hopeful.

[Julie G]

Welcome Chai! Excellent, albeit disheartening, link. The "improvement" may be nothing more than the lack of E4 carriers in the high dose arm...

[LanceS]

Sounded as if the trial used confusing Bayesian stats which along with the 4 removal/"downgraded dosage" has clouded the analysis, but the "scientific experts" feel pretty comfortable in the ability of the drug to reduce the "Beta load" (my 4/4 brain term not scientific) which seems pretty correlated with the tests measures of mental acuity. I get the disappointment, but this actually sounds pretty interesting because they say 4s get the "Beta load" first then decline happens as expected. (There are some data points that point toward accelerated decline for 4s, but this will probably be investigated more in future studies, which hopefully won't remove the APOE4s the way this study did) Anyway if you can tolerate the drug, the "scientific experts" seem to believe the "Beta load" will be reduced for APOE4s... this conclusion predicated on what happened to them in their "protected doseage cohort" and extrapolating that based on what happened to non 4s. Forgive the non scientific "" jargon.

I can't believe that Beta reduction gets you something. I thought science had moved on. Market response seemed pretty disappointed by the announcement but its always hard to tell what that really means. Were they pricing in widespread availability with no phase 3? etc etc? Either way it seems in 6-12 months we've gone from widespread ALZ program cancellations to a pretty enthusiastic result almost certain to get a few new compounds started.

https://www.alzforum.org/news/conferenc ... ve-decline

sorry more of a stream of consciousness post... steps and kid to pickup before the witching hour in the east

[Julie G]

Nice to see you posting, Lance! Here's more chatter about the chatter Biogen "success."

[LanceS]

Thanks Julie, I needed a little course correction!

Getting kids over the hump is tough, but I still pop on from time to time usually using the search function. Incredibly valuable community resource / asset even when not posting interacting. Bought some olive oil from AN the other day. Thanks! Hope you all are doing well. Cheers!