Cassava Sciences Announces Final Results of a Phase 2b Clinical Study of Sumifilam in Patients with Alzheimer’s Disease
Sep 14, 2020
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Alzheimer’s Patients in Drug Groups Showed Statistically Significant Improvements in Biomarkers of Disease Compared to Placebo Group (P<0.05)
Alzheimer’s Patients in Drug Groups Showed Improved Cognition Compared to Placebo Group (Effect Size 46-17%)
Sumifilam Was Safe and Well-Tolerated
COMPANY TO HOST CONFERENCE CALL TODAY AT 8:30 AM ET.
Conference Call Will Include Dr. Gonzalez-Rojas, MD, Principal Investigator on Both the Phase 2b Study of Sumifilam and an Ongoing, One-Year Open-Label Study of Sumifilam In Patients with Alzheimer’s Disease
AUSTIN, Texas, Sept. 14, 2020 (GLOBE NEWSWIRE) -- Cassava Sciences, Inc. (Nasdaq: SAVA) today announced final results of a Phase 2b study with its lead drug candidate, sumifilam, in Alzheimer’s disease. In a clinical study funded by the National Institutes of Health (NIH), sumifilam significantly improved an entire panel of validated biomarkers of disease in patients with Alzheimer’s disease. The ability to improve multiple biomarkers from distinct biological pathways with one drug has never been shown before in patients with Alzheimer’s disease. Study results are expected to be published in a peer-reviewed publication. Sumifilam is the first of a new class of drug compounds that bind to a protein called Filamin A.
“Filamin-binding molecules are new to Alzheimer’s research and may represent an important advance if these data can be replicated in larger studies,” said Jeffrey Cummings, M.D., Sc.D., Founding Director of the Cleveland Clinic Lou Ruvo Center for Brain Health, and Chambers Professor of Brain Science at the University of Nevada, Las Vegas. “I am pleased to see early evidence of disease-modifying effects in patients with this investigational drug. The data appear to represent a step forward toward urgently needed treatments for Alzheimer’s disease.”
In addition, Alzheimer’s patients treated with sumifilam showed directional improvements in tests of remembering new information, versus patients on placebo. Improvements in cognition correlated most strongly with decreases in P-tau181, a biomarker that, when elevated, leads to tangles in the brain. Sumifilam decreased brain levels of Ptau-181 by 8-11%, versus placebo.
In this study, Alzheimer’s patients treated with 50 mg or 100 mg of sumifilam twice-daily for 28 days showed statistically significant (p<0.05) improvements in biomarkers of disease pathology, neurodegeneration and neuroinflammation, versus Alzheimer’s patients who took placebo. In addition, Alzheimer’s patients treated with sumifilam showed directional improvements in validated tests of episodic memory and spatial working memory, versus patients on placebo (Effect Sizes 46-17%). Cognitive improvements correlated most strongly (R2=0.5) with decreases in P-tau181. The study achieved a 98% response rate, defined as the proportion of study participants taking sumifilam who showed improvements in biomarkers.
“The clinical data suggest sumifilam may be slowing disease progression in Alzheimer’s patients,” said Nadav Friedmann, PhD/MD, Chief Medical Officer, Cassava Sciences. “This exciting possibility will need to be evaluated in future collaborations with patients, physicians, advisors and others.”
“Other than a few drugs to help ease the decline, there’s really nothing out there to treat people with Alzheimer’s,” said Remi Barbier, Chairman, President & CEO, Cassava Sciences. “The improvement on multiple biomarkers in this clinical study is a first and offers hope that sumifilam has potential to become a transformative treatment for people with Alzheimer’s disease.”
Phase 2b Study Design
Phase 2b was a randomized, placebo-controlled, double-blind, multi-center clinical study of sumifilam (formerly, PTI-125). Sixty-four patients with mild-to-moderate Alzheimer’s disease, age 50-85, were randomized (1:1:1) to 100 mg or 50 mg oral sumifilam or matching placebo. Treatment was administered twice daily for 28 days. Nine U.S. study sites enrolled patients. A clinical diagnosis of Alzheimer’s disease was confirmed with the Mini-Mental State Examination (MMSE) =16 to =26 and a CSF T-tau/Aß42 ratio =0.28. Safety was assessed by ECGs, clinical labs, adverse event monitoring and physical examinations.
Phase 2b Study Results
In this study, drug was safe and well-tolerated, with no drug-related patient discontinuations. The study used biomarkers to measure drug effects. Biomarkers are objective biological endpoints used to track the progression of Alzheimer’s disease. Molecular aberrations in the brain are reflected in biomarkers found in cerebrospinal fluid (CSF), a fluid that surrounds the brain. A key objective of this study was to measure changes in levels of CSF biomarkers in study participants before and after 28 days of treatment (i.e., percent change from baseline).