After the recent controversy surrounding the approval of Biogen’s drug Adu, a lot of attention has been brought to the Alzheimer’s disease space. Time and again we have witnessed the failure of plaque reduction to translate into cognitive/functional benefits.
After recent success in there P2B trial & open label study extension, the FDA has approved Cassava Sciences Simufilam to start phase 3 trials this year. Simufilam has a differentiated mechanism of action—targeting a scaffolding protein Filamen A to tame neuroinflammation and neurodegeneration. Simufilam has shown a consistent set of positive data supporting the mechanism of action. The p2B trial results have been reported but have not yet finished peer review. The pre print can be found here. This helps explain the MOA of action well. https://www.researchsquare.com/article/rs-249858/v1
It can be summarize as followed:
“ In a randomized clinical trial of 64 patients with Alzheimer’s disease dementia, simufilam 50 or 100 mg significantly improved multiple biomarkers of Alzheimer’s disease, neurodegeneration, neuroinflammation and blood-brain barrier integrity, with no safety issues. Collectively, results of this randomized controlled trial are consistent with the drug’s mechanism of action and replicate a prior, open-label study.20
Increases in Aβ42 and reductions in total tau and p-Tau181 imply reduced Alzheimer’s disease pathophysiology. Reduced levels of neurofilament light chain and neurogranin suggest a slower rate of neurodegeneration. The 36% and 43% reductions in neurogranin, considered specific to Alzheimer’s disease,24 additionally suggest reduced disease pathology. Reductions in neuroinflammatory markers YKL-40, interleukin-6, sTREM2 and HMGB1 indicate suppressed neuroinflammation”
Patients who have completed the p2B trial have been enrolled in a one year open label study extension. The open label study when completed will have 150 patients. After one year of treatment of open label Simufilam, all patients will be enrolled in a Cognitive Maintenance study with half being placed on Simufilam vs half on placebo. On February 2nd of this year, Cassava released 6-month interim data from the first ~50 patients on the non-blinded open-label study of simu’ in AD. The analyses show an ~10% (1.6 points) mean improvement in cogniton as measured by the ADAS- cog11 scale. Additionally, these showed a 29% (1.3 points) improvement in dementia-related behavior (anxiety, delusions and agitation) as measured by the Neuropsychiatric Inventory at 6 months as compared to baseline. From my understanding, mild to moderate ALZ patients decline 5.5 points on average on Adas Cog scale per year. I understand the limitations of an open label study, especially in ALZ disease. However, there are two decades of research that shows cognition improvement in Alzheimer’s patients peak at 11 weeks and diminishes at 22weeks in patients who are taking placebo. I am unaware of any study where Alz patients on placebo have had cognitive improvements after 22 weeks. An improvement in cognition from 6 to 9 months along with its ability to show the reduction of biomarkers bodes very well for the success of Simufilam in its phase 3 trial. Simufilam has a differentiated MOA from treatments currently in use & trials, which acts to correct the misfolded protein Filamen A. This is a small molecule interaction whose affect theoretically should not wane over time, thus there should be no tolerance or resistance issues. There have been no safety signals to date in its trials and there are no known hypotheses for Simufilam to cause safety issues as well. Cassava Sciences is also working on a blood diagnostic test to detect Alzheimer’s disease. The results of this study will be available on Monday at AAIC. In theory, patients who have a positive test can be placed on Simufilam years before the onset of symptoms in AD. I remain cautiously optimistic for the success of Simufilam; ever since preclinical to P2, the drug is safe, biomarkers track improvement in neuroinflammation, neurodegeneration, and healthy BBB. Study data follows the MOA models and no interventions during all the studies so far. If you look at Biogen, Eli Lily, or any Big Pharma trials, they all showed problems that lead to interventions and some ultimately abandoned the trials. I have not heard of a AD trial as trouble free as Simufilam. “On Monday, July 26th, at approximately 10 am ET, scientists for Cassava Sciences will show a poster presentation at AAIC, titled “SavaDx, a Novel Plasma Biomarker to Detect Alzheimer’s Disease, Confirms Mechanism of Action of Simufilam”.
On Thursday, July 29th, at approximately 11 am ET, simufilam will be featured in a live podium presentation at AAIC, including a brief Q&A session. “
Submitted July 21, 2021 at 11:37PM by _SomeAverageGuy https://ift.tt/2UzmP3X
