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The federal indictment of Cassava Sciences’ (NASDAQ:SAVA) former lead scientist Hoau-Yan Wang and the resignations of CEO Remi Barbier and his spouse/researcher Lindsay Burns would appear like an ideal time for a reset for Cassava Sciences. New Govt Chairman Rick Barry has struck a extra conciliatory tone than his predecessor:
Taking up this present problem just isn’t about making Cassava’s share worth go up or attempting to silence the corporate’s many loud skeptics. These issues handle themselves if the corporate retains its give attention to Job#1. Our final objective is to develop an efficient remedy for a affected person inhabitants that has little hope and few therapeutic choices. What choices they presently have typically include extremely extreme antagonistic occasions (assertion).
What this implies for Cassava Sciences’ present and future litigation stays to be seen.
Cassava Sciences could have new management however it has doubled down each on simufilam’s mechanism of motion and the supposed positivity of section 2 scientific trial outcomes. Each give pause for concern. Certainly, the issues surrounding Cassava Sciences, albeit extra quietly, nonetheless swirl round and ultimately make FDA approval of simufilam a crap shoot at greatest. That’s the reason I give its inventory a promote suggestion.
Purported Mechanism of Motion
Cassava Sciences has cited 4 research which it contends confirms its rivalry that simufilam returns filamin A to its pure affirmation and in doing so eliminates amyloid’s toxicity by stopping its binding to varied receptors (presentation, p.15). Wang was the lead creator within the examine straight associated to Cassava Sciences’ purported mechanism of motion. One other examine concerned the inhibition or knockdown of filamin A not its reconfirmation in a mouse mannequin for pediatric epilepsy. A 3rd concerned the decreased phosphorylation of filamin A by simufilam (an in vitro examine for the remedy of pituitary most cancers). On this examine, simufilam appeared to activate somatostatin receptors which can improve the degradation of amyloid. The fourth includes the presence of insoluble (nitrated) filamin A throughout the very earliest phases of Alzheimer’s illness.
Simufilam could inhibit the phosphorylation and nitration of filamin A, however it doesn’t seem to reverse both. It might help the elimination of amyloid however this solely slows down the development of early stage Alzheimer’s illness after which solely in APOE4 carriers (analysis, determine 5). In brief, simufilam could result in modest short-term enhancements in cognition in delicate cognitive impairment sufferers and it could decelerate delicate Alzheimer’s illness for some time however it doesn’t modify illness development. That is proven within the numbers for Cassava Sciences’ section 2b scientific trials.
An Pressing Have to Revise the Numbers
Rick Barry fell again on the outdated Cassava Sciences declare that simufilam produces by no means earlier than seen leads to Alzheimer’s illness:
[Simufilam’s] outcomes have been in contrast to any Alzheimer’s trial ever, reporting secure cognition for 2 years in Alzheimer’s illness sufferers with delicate dementia (assertion).
The large drawback, although, was that this obvious stabilization was solely in these with delicate cognitive impairment to very delicate Alzheimer’s illness not in all delicate dementia sufferers. This group initially consisted of fifty sufferers who had a imply baseline ADAS-Cog rating of 15, not as Cassava Sciences claimed for the primary 133 sufferers with delicate dementia.
The baseline for the primary fifty sufferers went from 15 to 12.6 after one 12 months after which again to fifteen after two years. Nonetheless, Cassava Sciences added 10 sufferers outdoors of the trial protocol vary (i.e. MMSE scores of 26 or increased). The advance in those that accomplished twelve months of the trial was possible not 2.4 factors (15-12.6=2.4), however .9 factors (13.5-12.6=.9) (off). The drop between 12 months and 24 months from baseline would then be 1.5 factors (13.5 to fifteen). For Aricept/donpezil from a greater baseline (11.28) the numbers are as follows:
12 months: .17 decline
24 months: 1.22 decline
(desk two)
So simufilam seems to be higher than Aricept at one 12 months, however no higher than Aricept at two years as soon as adjusting for various baseline.
For solidly delicate Alzheimer’s illness, sufferers on simufilam declined by .5 factors at one 12 months (19.1 to 19.6). Gentle to average Alzheimer’s illness sufferers on simufilam declined to three factors between 12 and 18 months (calculated based mostly off the numbers supplied from the Cognition Upkeep Research for the primary fifty sufferers and the complete information set). The numbers for Aricept from a baseline of 20.7 are:
12 months: 1.1 decline
18 months: 4.2 decline
(desk three).
Simufilam seems to supply nearly the identical outcomes because the outdated commonplace of take care of solidly delicate Alzheimer’s illness, though it could be considerably safer.
To summarize, the mechanism of motion of simufilam has not been independently verified, and it solely slows down delicate Alzheimer’s illness for a 12 months.
Cassava Sciences continues to misrepresent which teams reply to simufilam. The FDA could or could not take discover of this, however with all the opposite controversy surrounding the drug, Cassava Sciences is unlikely to keep away from shut scrutiny. And that shut scrutiny is turning into an rising drawback for the corporate because it nears the tip of its first section 3 scientific trial.
Simufilam is far safer and sure more practical that the anti-amyloid antibody medicine accredited by the FDA and seems to be considerably safer and equally efficient as Aricept (which needs to be famous just isn’t accredited for the remedy of delicate cognitive impairment). However given all of its previous issues and its short-term and restricted effectiveness, the FDA might not be within the “temper” to grant one other “free go.”
