Cassava Sciences Inc (SAVA)

[sunspotter]

From FirstWorldPharma:

“ Cassava's candidate for Alzheimer's hits the drug development graveyard
Elizabeth S. Eaton
PUBLISHED : MARCH 25, 2025
Ref: GlobeNewswire

Cassava Sciences put the final nail in simufilam's coffin after the Alzheimer's disease candidate demonstrated no treatment benefit in a second late-stage study.

The company shared topline data on Tuesday from the REFOCUS-ALZ trial — which had been terminated in November when another Phase III study, RETHINK-ALZ, missed its co-primary endpoints — demonstrating that simufilam failed to meet all primary, secondary and exploratory biomarker measures. The oral small molecule targets the filamin A protein.

The 76-week REFOCUS-ALZ study had enrolled 1125 patients with mild-to-moderate Alzheimer's to receive either simufilam or placebo; the topline readout was based on results from "a large portion of subjects… [who] completed their final study visit prior to the termination of the trial," Cassava said.

The trial's two primary endpoints evaluated change in cognition and function from baseline, as measured by the Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-COG12) and Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scales.

"We are disappointed that the results of REFOCUS-ALZ and RETHINK-ALZ showed no treatment benefit for patients with mild-to-moderate Alzheimer’s disease. These results were unambiguous," said CEO Rick Barry. "Cassava will discontinue all efforts to develop simufilam for Alzheimer’s disease and we expect to phase out the programme by the end of Q2 2025."


The company's shares fell 32% on Tuesday to close at about $1.90. Cassava's valuation has now fallen more than 98% from its peak of $135.3 million in July 2021, when the company was riding high on data that suggested simufilam improved cognition and behaviour in patients with Alzheimer's, as well as a presentation at the Alzheimer's Association International Conference (AAIC) showing that the candidate significantly reduced plasma levels of altered filamin A and p-tau181 in patients after 28 days.

However, shares tumbled shortly afterward amid allegations that Cassava had manipulated its trial data, although the company denied all allegations. Specifically, a citizen's petition asked that the FDA order a halt of RETHINK-ALZ and REFOCUS-ALZ, highlighting "grave concerns about the quality and integrity" of lab-based studies on the oral drug, as well as a "long-standing pattern" of potential data manipulation in scientific papers and corporate disclosures. That petition was denied by the FDA in 2022.”