This article from yesterday: https://seekingalpha.com/article/4298721-biogen-amyloid-alzheimers-disease-rabbit-holeBiogen, Amyloid, And Alzheimer's Disease: Once More Down The Rabbit Hole
Biogen claims that its drug aducanumab reduces the rate of decline in early Alzheimer's disease by 23 percent.
This percentage is considerably less for non-APOE4 carriers and probably slightly less for APOE4 carriers.
The imbalance between a substantial number of APOE4 carriers in the placebo group versus a relatively few APOE4 carriers in the drug group may still be skewing the data.
I would recommend selling shares in Biogen before the data catches up with the claims.
It's helpful to see the counter-views on this news. I hope you don't mind that I put Lane Simonian's views in a quote box, so that they are easily distinguished from your post.
Here's my problem with his analysis: Both the central quote in his article, and the claim he makes that this study is flawed because more ApoE 4s were in the placebo arm (and so would be expected to do worse over time) is based on a completely different Biogen drug BAN2401
in a completely different study. He directly quotes from a conference in October 2018. He acknowledges that this is a different drug if you read carefully, but it's buried near the end of his article. Biogen is clear that the "arms" between placebo, low and high dose in aducanumab trials were balanced with about 2/3 of those receiving the placebo, the low, medium and high doses having one or two copies of ApoE 4.
It is true that Biogen
got approval to move all high-dose ApoE 4 carriers to a 10 mg dose. What may have diluted the results earlier is that the low-dose group was divided into a 3mg dose for ApoE 4 carriers and a 6 mg. dose for non-Apoe4 carriers (presumably due to fears of ARIA micro-bleeds with ApoE4). The high dose group was initially 6mg for ApoE4 and 10 mg for everyone else. That means the "low dose" group of ApoE 4 carriers, who may have had a higher risk of progression, actually got half the dose of non-ApoE carriers in the low-dose group.
It seems to be that the reason for the delayed results is that they finally had enough data on people taking a 10mg dose to realize how effective and safe it was.
To be balanced, it's not all rosy news: The 329 people who completed the Emerge study on a low dose of aducanumab, showed a 16% reduction in their decline on their CDR-SB baseline score compared to those on placebo. The 340 people who completed the Emerge study on the high dose showed a 23% reduction in their decline from baseline score compared to the placebo group. In the Engage trial, it appears that the high dose group actually showed a 6% increase compared to placebo, while the low dose group showed an 8% decrease, but neither of those met the criteria for statistical significance with the number of trial participants, meaning it's possible the results were due to chance.
However, the caregiver interviews in the AD Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version
showed a 46% reduction in decline of daily living skills compared to placebo group for the high dose participants, at the 0.0002 level of significance. These are people who do not know whether their loved one was getting a "sham" shot, a small dose or a high dose of aducanumab.
By the way, Biogen
plans to ask the FDA for approval to offer aducanumab to all participants who had been in the two trials. That would be consistent with what clinical trials call the Extension arm: completed trial participants are offered the active drug, without being told (I believe) whether they had been on the active drug or a placebo in the completed trial. Doesn't require the enormous approval process of a new trial, and allows for continued monitoring and up to a doubling in size of the treatment group.
Here's the link to the details I cited: https://investors.biogen.com/static-files/5a31a1e3-4fbb-4165-921a-f0ccb1d64b65