End looms for Cassava's simufilam in Alzheimer's disease

Cassava Sciences' troubled development of Alzheimer's disease candidate simufilam looks like it may have finally reached the end.

The Austin, Texas-based biotech revealed that simufilam failed its first phase 3 test in mild-to-moderate Alzheimer's and a second study has now been halted, leading to an 84% drop in its share price.

Simufilam – a small-molecule drug targeting filamin A, a different mechanism to the current crop of amyloid-targeting Alzheimer's therapies – failed to deliver a statistically significant improvement in cognition or reduce functional decline across any of the endpoints in the ReThink-ALZ study.

Cassava's chief executive, Rick Barry, said the result was "disappointing," suggesting that the loss of cognition was less pronounced in the placebo group than has been seen in other Alzheimer's studies, which would make it harder for simufilam to show a benefit.

"A result like this has implications on our second Phase 3 trial, ReFocus-ALZ," he added. "We have made the difficult decision to discontinue ReFocus-ALZ, given the nature of [the] reported results."

In the 804-subject study, simufilam-treated patients saw a 2.8-point change from baseline after 52 weeks on the ADAS-Cog12 cognition scale, while the placebo group saw a 3.2-point change, which was not a statistically significant difference.

Similarly, on the ADCS-ADL scale for functional ability, the simufilam group saw a 3.3% decline, which was not significantly different from the 3.8% fall with placebo.

Barry said the company is working to understand the results and will share detailed data at a future medical congress, but it's hard to see a way forward for the programme with both phase 3 trials now shelved.

The readout comes just a few weeks 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.

Shares in the company rocketed after that announcement, at one point trading above $120 in mid-2021, but have steadily declined since then and are currently trading at $4.30.

A Cassava-affiliated university scientist – City University of New York's Hoau-Yan Wang – was also accused of manipulating clinical trial results and agreed to pay $50,000 as part of the SEC agreement. Meanwhile, former Cassava CEO Remi Barbier and ex-head of neuroscience Dr Lindsay Burns settled for $175,000 and $85,000, respectively.

A company statement on the outcome indicated that it does not expect a separate investigation by the Department of Justice to lead to criminal charges or a further settlement.

Cassava was still sitting on around $150 million in cash at the end of the third quarter, but has little beyond simufilam in its pipeline other than an Alzheimer's diagnostic in early development.

Photo by Donald Giannatti on Unsplash