Annovis rises on Alzheimer’s froth

The data so far do not appear to justify quite this much excitement.

Investors who bought into Annovis Bio following Friday’s news of a mid-stage hit in Alzheimer’s disease may have acted a little precipitately. The company trumpeted a significant improvement in cognitive symptoms of the disease with ANVS401, and its stock leapt 127% to close at $60.

The magnitude of the improvement was indeed impressive – but there are several reasons why the cautious investor might have held back. The results come from just 14 patients; do not specify the dose used; and concern just one of the trial’s five functional endpoints. Worse, the placebo-adjusted benefit did not reach significance. With a $50m follow-on offering announced yesterday at $50 per share, some newcomers are at risk of getting burned. 

Annovis's phase 2a study aims to evaluate ANVS401, an inhibitor of amyloid precursor protein, tau and α-synuclein, in Alzheimer’s and Parkinson’s patients. The trial’s enrolment target is 68, but Annovis has been releasing data piecemeal. The day before the Alzheimer’s data came out it reported biomarker data from 14 Parkinson’s patients in the same study.

Mysteries

In the 14 Alzheimer’s subjects, a 4.4 point reduction in Adas-Cog11 was seen after 25 days of treatment with ANVS401. This reduction, of 30% from baseline, was statistically significant with a p value of 0.04. 

Annovis pointed out that this was substantially larger than reported by competitors. In the Emerge trial, Biogen’s aducanumab managed an improvement of 1.4-points from baseline in Adas-Cog13 after a year, and in February Cassava reported a 1.6-point improvement in Adas-Cog11 after six months’ treatment with simufilam.

But the comparison is hardly robust: for a start, the Cassava data came from 100 patients and Biogen’s from more than 1,500.

More importantly, any evidence that the improvement in cognition was due to ANVS401 rather than chance was derailed by the placebo group. The placebo-adjusted improvement in Adas-Cog11 was 3.3 points, or 22%, but at p=0.13 this fell short of statistical significance. 

Then there is the data Annovis’s release leaves out. According to clinicaltrials.gov the study has adverse events as the primary outcome – there have been no treatment-related AEs in the study so far – and drug plasma concentration as the secondary. There are five other endpoints, all symptom rating scales. Annovis has as yet offered no data on the other four. 

The trial is also intended to assess five dose levels, between 5mg and 80mg. The dose-ranging part of the trial has not yet commenced – but Annovis has not stated what dose was given to the 14 patients who have been treated. 

Future cuts from this trial will doubtless clear up some or all of these mysteries. For now it seems as if investors are leaping on Alzheimer’s stocks in case the coming approval decision for aducanumab lifts the whole sector. Biogen investors are not the only people with June 7 marked on their calendars. 
 

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