Yes, that’s why I wrote “I’d start with ezetimibe […] If you need to add a statin, add”. This means: “You START with ezetimibe then you test your apoB and if it’s still above your target you add another drug (bempedoic acid? low-dose statin? etc.).”

That being said, for hyperabsorbers, ezetimibe will most likely do the job. E4 carriers tend to be hyperabsorbers (source, I didn’t fact-check). So ezetimibe works for those who are the most at risk of AD.

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I didn’t miss that; just were setting expectations for people initiating ezetimibe monotherapy.

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I believe the “evidence” for reducing cholesterol synthesis in the brain = bad for Alzheimers comes from theories based on APOE alleles. APOE4 results in poor distribution of Cholesterol to neurons so it makes sense that you wouldn’t want to reduce Cholesterol concentrations in the brain. I’m not sure that’s “evidence”, circumstantial at best. That why I described it as “the prevailing thought”.

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Lp(a) reducing drug lepodisiran successful in phase 2 trials, phase 3 is ongoing.

https://investor.lilly.com/news-releases/news-release-details/lillys-lepodisiran-reduced-levels-genetically-inherited-heart

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Long duration it seems

  • Participants who received 400 mg of lepodisiran at both baseline and day 180 experienced a 94.8% reduction in average Lp(a) levels over the day 30 to 360 period, which remained 91.0% below baseline at day 360 (~1 year) and 74.2% below baseline at day 540 (~1.5 years)
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Any ETA on NDA filing with FDA?

@Nick1

Any ETA on NDA filing with FDA?

This one needs the phase three trials to first be fully enrolled and then read out the data of that

But there are others explicitly for Lp(a) and obicetrapib (for LDL, but still a big impact on Lp(a)) that seem to come out earlier

(Search the forum, recently discussed)

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