End of the line for Cassava's troubled Alzheimer's programme

The saga of Cassava Sciences' development of Alzheimer's disease therapy simufilam has come to its dismal end.

The company has reported top-line data from a second phase 3 trial of the drug, which showed that simufilam comprehensively failed to show any evidence of efficacy, missing primary endpoints looking at cognitive and functional decline as well as secondary and exploratory biomarker readouts.

After 76 weeks, the 1,125-subject REFOCUS-ALZ study found no improvement with simufilam on the Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-COG12) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scales compared to placebo.

The trial data follows just a few weeks after Cassava revealed that simufilam also failed to move the needle in the RETHINK-ALZ study, and the company has confirmed it will now end all development activities for the drug.

Simufilam is a small-molecule drug targeting filamin A, a different mechanism to the current crop of amyloid-targeting Alzheimer's therapies – Eisai/Biogen's Leqembi (lecanemab) and Eli Lilly's Kisunla (donanemab) – which were able to achieve modest but statistically significant improvements on cognition scores in late-stage testing.

Rick Barry, chief executive of the Austin, Texas-based biotech, said the results of the two trials were "unambiguous," having previously suggested that RETHINK-ALZ may have been compromised by a slower-than-expected loss of cognition in the placebo group. Development of simufilam for Alzheimer's will now be wound down by the end of the second quarter.

The end of the programme comes just a few months after Cassava was forced to pay $40 million to the Securities & Exchange Commission (SEC) to settle allegations that it made misleading statements about the results of its phase 2b trial of simufilam in Alzheimer's four years ago, without admitting wrongdoing. It has also been accused of disseminating falsified clinical trial data, a debacle that led to some high-profile resignations among its management.

Shares in the company have already been hammered by the SEC probe, which placed a spotlight on simufilam's efficacy, and lost another third of their value to close at $1.90 yesterday, giving the company a valuation of around $92 million. In mid-2021, just after reporting the mid-stage data, it had been trading above $120 per share.

The company ended 2024 with just under $127 million in cash reserves, and nothing in its pipeline beyond the Alzheimer's programme other than the potential use of simufilam for tuberous sclerosis complex (TSC)-related seizures, a condition that affects around 50,000 people in the US.

"While we have initiated preclinical studies to evaluate simufilam's potential as a treatment for TSC-related epilepsy, we maintain ongoing strategic expense management efforts," said Barry.

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