SAVA - Cassava Sciences' Simufilam Does Not Appear To Be Effective Against Alzheimer's Disease

2023-11-03 03:55:48 ET

Summary

• Cassava Sciences' presentation at the CTAD Conference undermines its claim that simufilam is an effective treatment for Alzheimer's Disease.
• The drug appears to have little to no effect on moderate Alzheimer's disease and only better for a year than placebo in mild Alzheimer's disease.
• The FDA is likely to scrutinize the allegations against the company, making it uncertain if simufilam will be approved.

For the time being, Cassava Sciences' (SAVA) has dusted off the controversy as to whether its principal scientist Dr. Hoau-Yan Wang discarded critical data related to the company's fundamental science ( article one , article two , Cassava Sciences' response ) The City University of New York's decision to pause its investigation following the explosive leak may have helped in this regard.

However, Cassava Sciences presented results at CTAD (Clinical Trials on Alzheimer's Disease) Conference that undermines its assertion that simufilam is an effective treatment for Alzheimer's Disease. At 12 months for moderate Alzheimer's disease, Cassava Sciences reported a 4.4 point decline in ADAS-Cog (Alzheimer's Disease Assessment Scale - Cognition Subscale) whereas a 5 to 6 point decline is expected for those on placebo over a similar time period. Between 12 and 18 months, the decline in those on simufilam and on placebo was almost exactly the same (as measured by Mini-Mental State Examination scores) ( chart, p. 21 ). Simufilam appears to have little to no effect on moderate Alzheimer's disease.

For mild Alzheimer's disease the analysis is complicated by the fact that Cassava Sciences did not separate between mild cognitive impairment (or very mild Alzheimer's Disease) and mild Alzheimer's disease. For the second fifty patients, many of whom had mild Alzheimer's disease, there was a .2 decline in ADAS-Cog scores at one year and the mean for the entire patient set was a .5 decline at one year. For mild Alzheimer's disease (which for Cassava Sciences includes those with mild cognitive impairment), almost no change was reported in baseline for those taking simufilam and placebo at twelve months (it is unclear in Cassava Sciences' model if the placebo data also included those taking Aricept or other acetylcholinesterase inhibitors). Between 12 and 18 months there is a slight separation between those on simufilam and placebo (chart p. 21).

Simufilam and Aricept perform better than placebo for twelve months for mild Alzheimer's Disease, but between 12 and 18 months neither outperforms placebo. And neither work much better than placebo at any point in moderate Alzheimer's Disease ( analysis from previous article one , analysis from previous article two ).

Cassava Sciences reported in the first group of fifty patients a 3.2 point improvement in those with mild to moderate Alzheimer's disease, but later data indicated a slight decline in those with mild Alzheimer's disease after one year and a 4.4 decline in those with moderate Alzheimer's disease. It is possible that for mild cognitive impairment, simufilam leads to improvements that may be sustainable for a period of time. It would take a much longer trial, though, to determine if the drug reduces the percentage of people advancing to Alzheimer's disease.

Except during its meteoric rise (which I felt was unjustified based on the existing data), I have consistently recommended holding Cassava Sciences, because I thought the numbers might be just good enough to gain FDA (Food and Drug Administration) approval. But as a series of allegations, investigation(s), and a trial continue to swirl around, I am no longer confident that the FDA will approve a drug that performs similarly to Aricept (although perhaps somewhat safer). The FDA has approved two anti-amyloid drugs from Biogen that perform little better than placebo in non-APOE4 carriers and can cause brain bleeds and brain swelling in APOE4 carriers. Because it does not remove amyloid, simufilam does not cause brain swelling and brain bleeds. And it is likely more effective than anti-amyloid drugs at least in non-APOE4 patients with mild cognitive impairment and with mild Alzheimer's disease (for about a year in the latter group). But Biogen cultivated a close relationship with the FDA, a relationship which to put it mildly CEO Remi Barbier has never had with the agency ( bad blood ). And the FDA is likely to take a close look at each and every allegation made against the company, when it comes time to making a decision on simufilam. That is why I now recommend selling stock in Cassava Sciences.

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