Benzinga | Sep 22, 2021 08:31AM EDT

Cassava Sciences Announces Top-Line Results Of 12-month Interim Analysis From Open-Label Study Evaluating Simufilam In Alzheimer's Disease; Says Cognition Scores Improved 3.2 Points On ADAS-Cog, Baseline To Month 12

* Cognition Scores Improved 3.2 Points on ADAS-Cog, Baseline to Month 12 (p<0.001)

* Two Independent Biostatisticians Analyzed Changes in ADAS-Cog Scores, Baseline to Month 12

* No Behavior Disorders on NPI in Over 50% Of Study Subjects at Month 12

* Initiation of Pivotal Phase 3 Clinical Program Remains On-track for Q4 2021, with Special Protocol Assessments from FDA

AUSTIN, Texas, Sept. 22, 2021 (GLOBE NEWSWIRE) -- Cassava Sciences, Inc. (NASDAQ:SAVA) announced top-line clinical data today from a pre-planned interim analysis of an on-going open-label study with its drug candidate simufilam in patients with mild-to-moderate Alzheimer's disease.

In a study funded by the National Institutes of Health (NIH), ADAS-Cog11 scores improved an average of 3.2 points from baseline (p<0.001) in the first 50 study subjects who completed 12 months of open-label treatment with simufilam. To emphasize impartiality, changes in ADAS-Cog scores baseline to month 12 were independently analyzed by two consulting biostatisticians.

"I feel energized and encouraged by the clinical data," said Remi Barbier, President & CEO. "We look forward to the initiation of a randomized, double-blind, placebo-controlled pivotal Phase 3 clinical program with simufilam in people with Alzheimer's disease."

Response Analysis

In the first 50 study subjects who completed 12 months of open-label treatment with simufilam:

* ADAS-Cog11 scores improved an average of 3.2 points from baseline (S.D. ? 6.3; p<0.001)

* 68% of study subjects improved on ADAS-Cog at 12 months; these study subjects improved an average of 6.8 points (S.D. ? 3.8)

* An additional 20% of study subjects declined less than 5 points on ADAS-Cog at 12 months; these study subjects declined an average of 2.5 points (S.D. ? 1.3)

An independent, published meta-analysis of patients with mild-to-moderate Alzheimer's disease reports an average decline of 5.5 points over 12 months1 amongst study subjects who were administered placebo in randomized, controlled trials.

Study subjects entered the open-label study with a clinical diagnosis of mild-to-moderate Alzheimer's, Mini-Mental State Examination (MMSE) range 16-26.

Safety Analysis

Drug is well-tolerated. There are no drug-related serious adverse events through the 12-month interim analysis.

Chain of Custody for Clinical Data

Investigator sites collect clinical data from study subjects. Sites enter their clinical data directly into an electronic data capture (EDC) system managed by an outside data management vendor. The data management vendor also maintains the clinical database. At Cassava Sciences' request, the data management vendor transmitted baseline and month-12 ADAS-Cog scores directly to two independent consulting biostatisticians for analysis. Both consultants hold PhD's in statistics and provide consulting expertise in support of medical research. One consultant is based in Texas, the other in Arizona. Both statisticians independently reached the same statistical conclusions on changes in ADAS-Cog scores, baseline to month 12.

Neuropsychiatric Inventory (NPI) at the 12 Month Interim Analysis

Alzheimer's is often accompanied by behaviors disorders, such as anxiety, agitation or delusions. These may become more frequent as disease progresses. The Neuropsychiatric Inventory (NPI) is a clinical tool widely used to measure changes in dementia-related behavior. At baseline, 34% of these study subjects had no neuropsychiatric symptoms on the NPI. At 12 months, over 50% had no neuropsychiatric symptoms on the NPI.

Clinical Strategy Around Open-label Study

Long-term safety data is a regulatory requirement. To collect these data, some drug development companies conduct an open-label study at the conclusion of a Phase 3 clinical testing program. Cassava Sciences believes it is prudent to conduct an open-label study before undertaking a large, complex and expensive Phase 3 clinical program in Alzheimer's disease: if an experimental drug for Alzheimer's fails to show long-term safety or any treatment benefit in a large, well-designed, open-label study, such drug is unlikely to succeed under the more rigorous conditions of a randomized, controlled trial. However, treatment effects observed in an open-label study are not proof of drug safety or efficacy, nor can open-label data predict clinical success in a Phase 3 program. Proof of safety and efficacy will always rest on results of a randomized, double-blind, placebo-controlled pivotal Phase 3 clinical program, which has not yet been conducted with simufilam.