DISCLAIMER: THIS IS NOT INVESTMENT ADVICE. I AM NOT A FINANCIAL ADVISOR. THIS IS FOR EDUCATIONAL PURPOSES ONLY. DO NOT USE THIS INFORMATION FOR INVESTMENTS --MAX HITEK
Be sure to visit Piotr Pietrzkiewicz's Patreon blog, "Bio_oko" , for many interesting articles related to drug development!
Blarcamesine versus Donepezil at 192 Weeks (for AD)
2025 04/15 (updated 2025 04/20)---Max Hitek
Definitions and Abbreviations
Blarcamesine - - Anavex's drug, also known as A2-73.
AD - - Alzheimer's Disease.
ADAS-Cog - - The Alzheimer's Disease Assessment Scale-Cognitive Subscale. Used to assess the severity of the cognitive impairment. Considered to be the gold standard. Version 13 is the current version used.
OLE - - Open Label Extension. Usually unblinded, follow up study.
SOC - - Standard Of Care.
Discussion
Anavex Life Sciences did a blinded 48 week Alzheimer’s Disease (AD) trial, using their drug Blarcamesine. This was a P2b/3 trial and, of course, had placebo data as the control. Anavex followed this trial with an open label extension(OLE) study, which lasted 192 weeks, and patients were treated with Blarcamesine for nearly 3 years. They recently published the long term results of this AD open label study (OLE). However, there is no placebo data, which is typical of long term OLE studies.
The Blarcamesine OLE results will be compared to the standard of care (SOC) for AD, which is Donepezil. Donepezil has been thoroughly studied, as it has been the SOC for decades. Both will be compared at 192 weeks, corresponding to the end of the Blarcamesine OLE trial data.
Donepezil has treatment data out to 254 weeks, as shown below.
It is useful to consider the Blarcamesine response at 192 weeks, versus the Donepezil response at 192 weeks.
The figure below is Donepezil data from European Neuropsychopharmacology1 (2000). This presumably is ADAS-Cog11 data, judging from the year it was published.
We can see that Donepezil was down ~24 pts from baseline at 192 wks. Again, assuming this is ADAS-Cog11 data, simple scaling can be used to approximate it to the newer ADAS-Cog13 scale. The approximate ADAS-Cog13 score for Donepezil would be 29.14pts. This can now be “apples to apples” compared to the Blarcamesine 192 week ADAS-Cog13 treated score (16pts).
Anavex presented their long term OLE data at the AD/PD2025 conference.2 Below is the slide, from their presentation, showing the Blarcamesine decline from baseline(0) in ADAS-Cog13 points. We are interested in the “Early Start”, light blue line. Disregard the gray and dark blue line.
I modified the plot to accommodate the Donepezil data, which is in the bottom right corner as a visual reference.
The 192 week Blarcamesine point (~16pts) and the Donepezil point(~29.1) represent the decline in cognition from the start of the trial. So, smaller numbers are better.
According to Anavex’s report3 on the 48 week trial, 69.1% of the Blarcamesine treated patients were also taking a Acetylcholinesterase inhibitor, which was Donepezil. So the Blarcamesine efficacy, was generally, in addition to the Donepezil improvements!
Conclusion
Though Anavex did not have a placebo reference for their OLE data, the SOC Donepezil provides a well known reference. At 192 weeks, Blarcamesine performed 45% better than Donepezil, even though most of the patients were already taking Donepezil!
References:
1"Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: final analysis of a US multicentre open-label study", European Neuropsychopharmacology, May 2000, by S.L Rogers (et al)
2Anavex presentation. AD/PD2025, Anavex presentation on April,5, 2025. "Phase IIb/III ATTENTION-AD Study: Over Three Years of Continuous Treatment with Oral BlarcamesineContinues to Significantly Benefit Early Alzheimer’s Disease Patients"
3The Journal of Prevention of Alzheimer’s Disease, 2004 November. "Blarcamesine for the treatment of Early Alzheimer’s Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial". By Stephen Macfarlane, et al.