Cassava Sciences (SAVA) Announces Positive End-of-Phase 2 Meeting with FDA and Outlines Pivotal Phase 3 Program for Simufilam in Alzheimer’s Disease

February 22, 2021 8:30 AM EST

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Cassava Sciences, Inc. (Nasdaq: SAVA), a biotechnology company developing product candidates for Alzheimer’s disease, today announced the successful completion of an End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) for simufilam, its lead drug candidate for the treatment of Alzheimer’s disease. Official EOP2 meeting minutes indicate FDA and Cassava Sciences agree on key elements of a pivotal Phase 3 clinical program in support of a New Drug Application (NDA) filing for simufilam in Alzheimer’s disease. Agreements reached during the EOP2 meeting show a clear path forward for advancing simufilam into Phase 3 studies in the second half of 2021.

“For over 10 years we’ve been doing basic research and early drug development with simufilam,” said Remi Barbier, President & CEO. “We are excited to finally advance simufilam into pivotal Phase 3 clinical studies in people with Alzheimer’s disease. We believe the underlying science is solid, the drug appears safe and the clinical roadmap makes sense. We’ve crossed the Rubicon.”

“We appreciate the valuable guidance and flexibility FDA has provided,” added Jim Kupiec, MD, Cassava Sciences’ Chief Clinical Development Officer. “We look forward to continuing a collaborative dialogue throughout the pivotal Phase 3 clinical development program.”

Simufilam is a novel drug, discovered at Cassava Sciences, that targets both neuroinflammation and neurodegeneration. The EOP2 meeting discussion was supported by years of scientific and clinical data, including positive results from a previously completed Phase 2 clinical program with simufilam in Alzheimer’s disease. In a double-blind, randomized, placebo-controlled Phase 2b study, simufilam demonstrated robust effects on primary and secondary outcome measures, with no safety issues. Recently, the Company announced that simufilam improved cognition in subjects with Alzheimer’s disease in a 6-month interim analysis of an open-label study, with no safety issues.

The EOP2 meeting took place mid-January. FDA attendees included Robert Temple, MD, Deputy Center Director for Clinical Science and Senior Advisor in the Office of New Drugs; Billy Dunn, MD, Director, Office of Neuroscience; Eric Bastings, MD, Director, Division of Neurology, and others.

Official meeting minutes confirm that Cassava Sciences and FDA are aligned on key elements of a Phase 3 clinical program for simufilam. FDA has agreed that the completed Phase 2 program, together with an upcoming and well-defined Phase 3 clinical program, are sufficient to show evidence of clinical efficacy for simufilam in Alzheimer’s disease. There is also agreement that the use of separate clinical scales to assess cognition (ADAS-cog1) and function (ADCS-ADL2) are appropriate co-primary endpoints of efficacy. A clinical scale that combines cognition and function, such as iADRS3, is a secondary efficacy endpoint.

Cassava Sciences’ pivotal Phase 3 clinical program consists of two double-blind, randomized, placebo-controlled studies, each described below.

Cassava Sciences’ first Phase 3 study is designed to evaluate disease-modifying effects of simufilam in Alzheimer’s disease. The goal is to demonstrate a slower rate of decline in cognition and health function in subjects treated with simufilam compared to placebo.

Details of the first Phase 3 study include:

  • Approximately 1,000 subjects with mild-to-moderate Alzheimer’s disease to be enrolled.
  • Subjects to be randomized (1:1:1) to simufilam 100 mg, 50 mg, or placebo BID.
  • Subjects to be treated for 18 months.
  • The co-primary efficacy endpoints are ADAS-Cog, a cognitive scale, and ADCS-ADL, a functional scale; both are widely used clinical tools in trials of Alzheimer’s disease.
  • A secondary efficacy endpoint is iADRS, a widely used clinical tool in trials of Alzheimer’s disease that combines cognitive and functional scores from ADAS-Cog & ADCS-ADL.
  • Other secondary endpoints include biomarkers of disease and NPI4, a clinical tool that assesses the presence and severity of dementia-related behavior.
  • The Company plans to initiate the first pivotal Phase 3 study Q3 2021.

Cassava Sciences’ second Phase 3 study is designed to evaluate symptomatic improvement in Alzheimer’s disease. The goal is to demonstrate improved cognition and health function in subjects treated with simufilam compared to placebo.

Details of the second Phase 3 study include:

  • Approximately 600 subjects with mild-to-moderate Alzheimer’s disease to be enrolled.
  • Subjects to be randomized (1:1) to simufilam 100 mg or placebo BID.
  • Subjects to be treated for 9 to 12 months.
  • The co-primary efficacy endpoints are ADAS-Cog, a cognitive scale, and ADCS-ADL, a functional scale; both are widely used clinical tools in trials of Alzheimer’s disease.
  • A secondary efficacy endpoint is iADRS, a widely used clinical tool in trials of Alzheimer’s disease that combines cognitive and functional scores from ADAS-Cog & ADCS-ADL.
  • Other secondary endpoints include biomarkers of disease and NPI, a clinical tool that assesses the presence and severity of dementia-related behavior.
  • The Company plans to initiate the second pivotal Phase 3 study Q4 2021.

FDA has provided further flexibility to Cassava Sciences by agreeing to review the final version of each protocol for the two Phase 3 studies, and to conduct a Special Protocol Assessment (SPA) for each Phase 3 study. An SPA is a formal regulatory procedure that confirms certain critical details of a Phase 3 study protocol, such as the statistical analyses, meet FDA’s standards of approvability.

In addition to the planned pivotal Phase 3 clinical program, other clinical studies in support of simufilam’s safety and efficacy in Alzheimer’s disease are briefly described below.

Open-label StudyCassava Sciences recently expanded the size of an ongoing open-label study of simufilam. The study’s target enrollment was increased by up to 50 additional subjects with mild-to-moderate Alzheimer’s disease, for a total target enrollment of up to 150 subjects. To accommodate increased enrollment, the Company is opening new clinical sites in the U.S. and Canada.

The Company plans to conduct a second interim analysis of the open-label study mid-year 2021, when approximately 50 subjects complete 12 months of drug treatment. Much like the first pre-planned interim analysis (6 months), the second pre-planned interim analysis (12 months) is expected to generate clinical data around long-term safety, cognition and dementia-related behavior.

Cognition Maintenance Study (CMS)In Q2 2021, Cassava Sciences plans to initiate a double-blind, randomized, placebo-controlled study in subjects with Alzheimer’s disease who have completed at least one year of open-label treatment with simufilam. In this Cognition Maintenance Study (CMS), subjects who complete one year of open-label treatment will be randomized (1:1) to simufilam or placebo for 6 months. The CMS is designed to compare simufilam’s effects on cognition and dementia-related in subjects who continue with drug treatment versus those who discontinue drug treatment. For ethical and other reasons, subjects who successfully complete the 6-month CMS will be given the option to return to open-label simufilam again.

Slide DeckCassava Sciences’ latest corporate presentation is available on its website under the Investors/Presentations page: https://www.CassavaSciences.com



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