Cassava Sciences’ phase 3 Alzheimer’s disease trial has missed its co-primary endpoints. With the study also missing secondary and exploratory biomarker endpoints, the biotech has pulled the plug on another phase 3 trial and an open-label extension.
The phase 3 trial compared simufilam, a small molecule that targets the filamin A protein, to placebo in more than 800 people with mild-to-moderate Alzheimer’s. After 52 weeks, the changes from baseline on scales of cognitive and functional impairment—ADAS-COG12 and ADCS-ADL—were no better in the drug candidate cohort than the placebo group.
On ADAS-COG12, where lower numbers mean less cognitive impairment, scores rose by 2.8 points on simufilam and 3.2 points on placebo. On ADCS-ADL, where higher numbers mean less functional impairment, scores fell by 3.3 points on simufilam and 3.8 points on placebo.
Neither result was statistically significant, with the p values coming in at 0.43 and 0.40. Cassava did a topline analysis of mild and moderate patient subgroups but again failed to show statistically significant improvements. The biotech also reported the failure of secondary and exploratory biomarker endpoints.
Cassava CEO Rick Barry said “the loss of cognition in the placebo group was less pronounced than was previously reported in other placebo-controlled studies” in Alzheimer’s. The biotech is working to figure out why that happened but didn’t use the placebo response to make the case that simufilam may work. Rather, Cassava stopped a second phase 3 trial and an open-label extension.
The biotech said it will continue to review the data and evaluate next steps. Cassava ended the third quarter with $149 million in cash and equivalents and said it is “committed to enhancing shareholder value.” The company held a conference call but largely repeated information in the press release and didn’t take questions because there is “still a tremendous amount that we don't know.”
Simufilam’s controversial development primed people to suspect a failure but the stock still fell 85% to below $4 in premarket trading. Cassava agreed to pay $40 million to resolve an investigation into claims it made misleading statements about phase 2b data earlier this year. The controversies go further back. PLOS One retracted papers about the underlying science, which were published in 2008 and 2009.