This Blog Is Only For Educational Purposes. Do Not Trade On This Blog Alone. Do Your Due Deligence or Consult Professional.
It was suggested to me to comparing the hypothetical performance of Blarcamesine in phase 2b/3 to Donezepil. Hat Tip to @Trainguy1. I tried to compare the 3 drugs, including 9 months performnace of Simufilam, to Donezepil as it was formated or presented in Fig. 2 on Donezepil Label coming with the drug, and FDA approved.
Following fact have to be kept in mind.
Donezepil performance is at the apogeum, that is at 24 weeks or about 6 months. Later, it deteriorates and cognitive scores decline. The other fact about Donezepil is that the trial included patients below 20 MMSE points. Namely, 26 >= MMSE >=10. This is the mild and moderate dementia due to Alzheimer’s. I plotted only the performance of the 10mg dose.
Blarcamesine performance projection was based on performance in phase2a, genetic classes i.e. SIGMAR1 and APOE4, and statistical distribution of classes in general population of Alzheimer’s patients. There is no way to assess at this point the consequences of limiting the population intent to treat to only patients with mild dementia i.e. MMSE >=20 points. The phase 2a included patients with moderate dementia as well as mild. This change in enrollment might alter the shape of curve and its proportions. In other words, plotted is the worst projected case for Blarcamesine. Also, the curve is not very well defined as only few points are provided. I am going to return to this graph, once more data can be available after December 1, 2022.
Simufilam performance was plotted with limiting the number of sample point to 10 from 50. also the duration of study is 9 months, and the criteria for enrollment. I think that Simufilam Open Label trial limits the enrollment to mild cases as the mean MMSE score is 25.7 MMSE points. So, this can be taken to be comparable to Blarcamesine but should in principle provide Simufilam better chances of success. The tendency in the field of Alzheimer’s trials is to treat the disease as early as possible i.e. at higher MMSE scores than 20 points. It is thought that with advancement into dementia the patients cross the point of no return due to the atrophy of too many brain cells.
In case of Donezepil and Simufilam the information is solid and the number of points sufficient to plot the performance curve, on the other hand Blarcamesine represents a case of an educated guess.
From the left to the right the ADAS-Cog11 scores of change from baseline move from improvement to mcognitive decline. As we move up on the y-axis we are given the percentage of patients who perform better than corresponding value of cognition for that point on the x-axis.
Plot comaparing the absolute performances of Donezepil, Simufilam and possibly Blarcamesine.
The black line represents the Donezepil 10mg 24 weeks trial with mild and moderate patients. This is the best donezepil can deliver. Violet line is the plott for Simufilam at 9 months of dosing. Subsequent results for Simufilam were not radically different from the presented 9 months data on changes from baseline for 50 patients. The red line is projection for Blarcamsine which was expalined in my previous posts, with methodology and other plots.
To my surprise, simufilam at 9 months has not been doing much better than Donezepil at 24 weeks. What we have to remember is that this is the best Donezepil can provide to a patients. After 24 weeks Donezepil can not hold these results. It will be seen if Simufilam could hold scores or even improve them over longer period of time. The lates is that simufilam has improved scores frommean of -3 ADAS-Cog11 change from baseline to -3.2 mean over additional 3 months, altogether 12 months of dosing.
Projcected Blarcamesine performance suggests that for up to 70% of patients the effect is better than for Simufilam or Donezepil, with the core of definitely better performance of some 55% as at the most left region the scores are converging for all 3 drugs, probably due to the ramdoness and repeatability of test scores over such sort time period. Then again, the most pressing question is whether these improvements can be held over time. Here, the key are the open label trial extensions. However the approval can be made on the relatively short time span performance, the real value of the drug lies in its extended performance which can only be evaluated over at least 3 years of dosing. Blarcamesine has already accumulated enough data to definitevly answer this question, but the company has not released detailed data on longevity of efficacy.
I am actually shocked by the mediocre performance of Simufilam as compared to Donezepil. The only saving grace in this situation for Simufilam can be holding the scores over time.
Make a one-time donation
Make a monthly donation
Make a yearly donation
Choose an amount
Or enter a custom amount
Your contribution is appreciated.
Your contribution is appreciated.
Your contribution is appreciated.DonateDonate monthlyDonate yearly