Cassava Sciences $SAVA (+1.08%)
and the fraud in the development of Alzheimer's drugs

Cassava Sciences $SAVA (+1.08%) a biopharmaceutical company based in Austin, Texas, focuses on the development of innovative therapies and diagnostics for neurodegenerative diseases, particularly Alzheimer's disease. The company specializes in two main projects:

• Simufilaman oral drug that aims to inhibit the altered protein filamin A (FLNA) in the brain of Alzheimer's patients. This stabilization is intended to prevent both neurodegeneration(1) as well as neuroinflammation(2) should be reduced.

• SavaDxA diagnostic product developed to detect Alzheimer's disease from a blood sample. The aim of this test is to diagnose Alzheimer's early and facilitate monitoring of the disease.

Failure of phase 3 trials of simufilam:

• The results of the ReThink ALZ Phase 3 study were very disappointing, as the drug simufilam failed to meet the pre-defined co-primary, secondary and exploratory endpoints. It showed no significant effect on either cognitive or functional decline in patients with mild to moderate Alzheimer's disease compared to a placebo.
• Due to this failure Cassava Sciences decided to also discontinue the second Phase 3 study (ReFocus-ALZ) and an open-label extension study.

• The news about the studies caused Cassava Sciences' share price to plummet by more than 80%.

• Cassava Sciences has long been accused of data manipulation for some time. In particular, there are allegations that clinical results from earlier studies, such as the Phase 2b studywere deliberately distorted in order to exaggerate the efficacy of simufilam. The SEC has charged Cassava Sciences and individual management, including founder and former CEO Remi Barbierfor making misleading statements about the results of these studies.

• In addition to the legal allegations, the study design is also being criticized. In particular, it should be emphasized that the cognitive decline in the placebo group of the ReThink-ALZ study was less pronounced than in previous Alzheimer's studies. This made it difficult to interpret the results and could indicate that external factors influenced the study results.

Challenges in Alzheimer's research

• The development of new drugs against Alzheimer's disease is associated with high risks, as demonstrated by the failure of simufilam impressively illustrates. Alzheimer's poses an enormous challenge for research due to the complex pathophysiology of the disease.

Future prospects

• Despite the setback with simufilam Cassava Sciences continues to pursue the development of SavaDxwhich could potentially revolutionize the early detection and monitoring of Alzheimer's disease. However, to be successful in the long term, the company will not only have to address the methodological weaknesses of its studies, but also rebuild the trust damaged by the legal disputes.