Celebration Thread! Biogen is going to the FDA with Aducan.

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J11
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Lecanemab treatment met the primary endpoint and reduced clinical decline on the global cognitive and functional scale, CDR-SB, compared with placebo at 18 months by 27%, which represents a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of Intent-to-treat (ITT) population. Clarity (NCT03887455).

-0.45 (p=0.00005) that is simply beyond reasonable argument.
This is before post-hoc searching for responders with above average amyloid clearance.



The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), an adverse event associated with anti-amyloid antibodies, was 12.5% in the lecanemab group and 1.7% in the placebo group. The incidence of symptomatic ARIA-E was 2.8% in the lecanemab group and 0.0% in the placebo group. The ARIA-H (ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) rate was 17.0% in the lecanemab group and 8.7% in the placebo group. The incidence of symptomatic ARIA-H was 0.7% in the lecanemab group and 0.2% in the placebo group.

As expected these rates of ARIA are much lower than what we have become accustomed to. These numbers are probably using IV dosing which we now know creates multiple times more ARIA than subcu dosing without any marginal benefit.
Last edited by J11 on Mon Oct 03, 2022 12:15 pm, edited 7 times in total.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Solid; solid result. As shown in the figure above 0.45 with around 0.30 SUVR (not reported) (m= ~1.4) would put Clarity right on the regression line. 0.45 CDR-sb benefit with 27% reduction versus placebo is right where we expected it to be.

We had our cake (result on the regression line) and ate it too (result leftwards on the regression line with low p-value).
Last edited by J11 on Wed Sep 28, 2022 3:53 pm, edited 1 time in total.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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J11 wrote: Wed Sep 28, 2022 2:55 pm Um, did Biogen really just go up $78 per share? I am guessing there's good news!! Yeah!
Um, yes. For context: that's a 39% increase in stock price in one day. And no, I don't have an investment in the stock--unless my mutual fund is now happy. Here's the press release:
https://investors.biogen.com/news-relea ... et-primary And for those wondering, the reason this release is to investors, is because the SEC mandates that all investors hear news at the same time to avoid insider trading.

And here's an interesting analysis in WAPO from someone who admits to having been very skeptical:
New Alzheimer’s Drug From Biogen and Eisai Is Just the Beginning
4/4 and still an optimist!
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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This is amazing! I suppose that I will need to celebrate sans cashews.
This is a solid stand up double or possibly even a slide into third for a triple.
Very strong result.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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What does the Clarity result mean for APOE e4s?
The above purple box to the lower left is the estimate for the e4+ result.
This was the 1.9 - 2.0 slope that we saw earlier.

So, ... with ~0.30 SUVR removal as suggested by today's 0.45 CDR-sb topline, best guess is that the e4s had a benefit of ~0.65 CDR-sb which is starting to move up there. We saw in previous results how most of the benefit acrrued to the e4s. This result could be even better for the e44s. The e4s had good correlation for both the Aducanumab phase 3s and the Lecanemab phase 2 as seen in the figure. Clarity could fit right in as expected with these earlier results.

Good to point out that the 0.45 CDR-sb representing a 27% slowing implies a 1.67 placebo decline which is right in line with where placebo should be. Probably should compare e4 treated with e4 placebo, though 0.65/1.67 is a ~40% slowing for the e4s. It is no longer plausible to not call this a clinically meaningful amount.

{Note: There is somewhat of a fallacy in the above thinking; I am assuming what I am trying to prove. Yet, without the actual numbers it is not easy to do otherwise.

With 3/4 s of patients as e4s-- 0.60 (3/4) = ~0.45 and
With 1/4 s of patients as none4s -- 0.10(1/4) = ~0.025 --> 0.45 + 0.025 = 0.47.

So ~0.60 for the e4s is about right. Will need to look around to see what the e4 percent was in Clarity/}

OK a report for Lecanemab Clarity had 1,231 e4 patients (excluding China) of 1795 which was 68.6% E4s. If anything China has a lower population e4 percent.

0.60 (0.686) = 0.412 e4
~0.12 (0.314) = 0.038 non e4 --> 0.412 + 0.038 = 0.45
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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NF52, yes the stock might have been up 39% though the out of the money calls were up a fair amount more than that.
For whatever reason, Eisai was only up 17%. I guess that Eiasi is more of an integrated phrama versus Biogen which is more of a leveraged biotech.

I am looking back on my post of Sat Sep 17, 2022 10:18 pm when I was pre-specifying the readout. I think that my call for the e4s of ~ 0.6 CDR-sb benefit was not bad; from what we know now that was likely pretty much the number that will be reported. It is always better to call the 8 ball in the corner before you play and not after.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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This is amazing!

They hit all the other secondary's as well. This read out cleanly across the board! Some of the others like ADCOMS and iADRS are better measures; they also achieved significance. Would like more details, though what we have now seems unequivocal and it is in complete alignment with previous thread regressions.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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J11 wrote: Wed Sep 28, 2022 5:35 pm This is amazing!

They hit all the other secondary's as well. This read out cleanly across the board! Some of the others like ADCOMS and iADRS are better measures; they also achieved significance. Would like more details, though what we have now seems unequivocal and it is in complete alignment with previous thread regressions.
If not before, we should have detailed information at the CTAD conference the last week in November. Hitting all pre-specified outcomes, several of which are themselves composites of multiple cognitive skills and one, IADRs, a composite of Activities of Daily Living, seems to me like landing a 10 on an overall gymnastics routine. To see the divergence of lines between people in the placebo group and those on lecanemab raises a question for doubters: “Would you be okay with the placebo if given the option of lecanemab if you saw this prediction after an MCI diagnosis?”
Especially given that the incidence of moderate to severe ARIA should be much lower with subcutaneous dosing.
4/4 and still an optimist!
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