From Cassava Sciences
Remi Barbier, President & CEO of Cassava Sciences, said, “For over 10 years we’ve been doing basic research and early drug development with simufilam. 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.”
Jim Kupiec, MD, Chief Clinical Development Officer of Cassava Sciences, added, “We appreciate the valuable guidance and flexibility FDA has provided,” added “We look forward to continuing a collaborative dialogue throughout the pivotal Phase 3 clinical development program.”
About Simulfilam
Simufilam targets both neuroinflammation and neurodegeneration. The product is a proprietary, oral small molecule drug that aims at restoring the normal shape and function of altered filamin – a scaffolding protein, in the brain. The Altered FLNA in the brain is what is believed to disrupt the normal function of neurons, leading to Alzheimer’s pathology, neurodegeneration and neuroinflammation. The underlying science for simufilam is published in peer-reviewed journals including the following: Journal of Neuroscience, Neurobiology of Aging, Journal of Biological Chemistry, Neuroimmunology and Neuroinflammation and Journal of Prevention of Alzheimer’s Disease.
Cassava Sciences is also developing an investigational diagnostic called, SavaDx, to detect Alzheimer’s disease with a simple blood test.
Simufilam and SavaDx are both developed in-house. Both product candidates are substantially funded by peer-review research grant awards from the National Institutes of Health (NIH).
Cassava Sciences owns worldwide development and commercial rights to its research programs in Alzheimer’s disease, and related technologies, without royalty obligations to any third party.
Phase 2b Study
In a double-blind, randomized, placebo-controlled Phase 2b study, simufilam demonstrated robust effects on primary and secondary outcome measures, with no safety issues. The firm has also 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
The EOP2 meeting took place in 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.
The official meeting minutes confirm that Cassava Sciences and FDA are aligned on key elements of the Phase 3 clinical program for simufilam.
The 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.
Cassava Sciences First Phase 3 Study:
This study is designed to evaluate disease-modifying effects of simufilam in Alzheimer’s disease. The goal of this study 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 in Q3 2021.
Cassava Sciences Second Phase 3 Study:
This 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 in Q4 2021.
The 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.
What is an SPA?
An SPA is a formal regulatory procedure that confirms certain critical details of a Phase 3 study protocol, such as the statistical analyses, that 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 Study
Cassava 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.
Prohost Observations
Cassava looks good, with solid science and knowledge. The mid-Phase results have been exciting as they demonstrated improvements that have never been observed at any time before on anybody treated with the many experimental products developed by many firms for the treatment of Alzheimer’s diseases.
We picked SAVA when it was trading at around $9.
Today SAVA is trading at $ 51.25 Down $1.77.
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Cassava Sciences
Cassava Sciences (SAVA) announced the successful completion of an End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) for simufilam, its drug candidate for Alzheimer’s disease.
The official EOP2 meeting minutes indicate that the FDA and Cassava Sciences have agreed 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.
The agreements reached during the meeting have demonstrated a clear path forward for advancing simufilam into Phase 3 studies in the second half of 2021. The 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.
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