Latest news with #Simufilam
Reuters
25-03-2025
- Business
- Reuters
Cassava to discontinue development of Alzheimer's disease drug
March 25 (Reuters) - Cassava Sciences (SAVA.O), opens new tab said on Tuesday it will discontinue the development of its experimental treatment simufilam for Alzheimer's disease, after data showed the drug did not meet the main and secondary goals in a late-stage trial. The drug developer's shares were up nearly 2% in premarket trading. Keep up with the latest medical breakthroughs and healthcare trends with the Reuters Health Rounds newsletter. Sign up here. The late-stage trial had the main and secondary goals of significantly reducing cognitive and functional decline in patients with mild-to-moderate Alzheimer's disease. Simufilam has been at the center of scrutiny after a medical professor linked to its development was charged with fraud in June. The company expects to phase out the program by the end of the second quarter, it said.
Associated Press
25-03-2025
- Business
- Associated Press
Cassava Sciences Reports Topline Phase 3 REFOCUS-ALZ Data
Simufilam did not show a significant reduction in co-primary endpoints of cognitive or functional decline versus placebo in patients with mild-to-moderate Alzheimer's disease Simufilam continued to demonstrate an overall favorable safety profile Cassava's Alzheimer's disease development program with simufilam will be completely discontinued by the end of Q2 2025 AUSTIN, Texas, March 25, 2025 (GLOBE NEWSWIRE) -- Cassava Sciences, Inc. (NASDAQ: SAVA, 'Cassava', the 'Company'), a clinical-stage biotechnology company focused on developing a novel, investigational treatment for central nervous system disorders, including Alzheimer's disease (AD) dementia and tuberous sclerosis complex (TSC)-related epilepsy, today shared topline results from the Phase 3 REFOCUS-ALZ study of simufilam in mild-to-moderate AD. Topline data indicate that REFOCUS-ALZ did not meet each of the prespecified co-primary, secondary and exploratory biomarker endpoints. The co-primary endpoints were the change in cognition and function from baseline to the end of the double-blind treatment period at week 76, assessed by the ADAS-COG12 and ADCS-ADL scales, comparing simufilam to placebo. REFOCUS-ALZ enrolled 1,125 patients and was discontinued on November 25, 2024, following the report that a prior 52-week Phase 3 study, RETHINK-ALZ, did not meet its co-primary endpoints. A large portion of subjects enrolled in REFOCUS-ALZ completed their final study visit prior to the termination of the trial. Simufilam continued to demonstrate an overall favorable safety profile. 'We are disappointed that the results of REFOCUS-ALZ and RETHINK-ALZ showed no treatment benefit for patients with mild-to-moderate Alzheimer's disease. These results were unambiguous. Working with patients, their families and their caregivers has brought a special dignity to our Phase 3 Alzheimer's disease clinical trial program and to each of us at Cassava. We are deeply grateful for the dedication and committed efforts of study investigators and site teams, who enabled us to conduct these trials with integrity and scientific rigor and whose efforts provided a clear data read out,' said Rick Barry, President and Chief Executive Officer of Cassava. 'Cassava will discontinue all efforts to develop simufilam for Alzheimer's disease and we expect to phase out the program by the end of Q2 2025,' continued Mr. Barry. 'We remain dedicated to our mission of developing novel medicines for central nervous system disorders. While we have initiated preclinical studies to evaluate simufilam's potential as a treatment for TSC-related epilepsy, we maintain ongoing strategic expense management efforts.' Eric Schoen, Chief Financial Officer of Cassava commented, 'We remain focused on the interests of Cassava shareholders and are committed to enhancing shareholder value. Cassava is well-capitalized with approximately $128.6 million in cash and cash equivalents as of December 31, 2024.' Summary Study Results: Primary Endpoint Data Co-Primary Endpoints LS means change from baseline to the end of the double-blind treatment period N=372 N=376 N=372 ADAS-COG12 (±SE) 4.97 (± 0.46) 4.70 (± 0.46) 0.27 (± 0.63) P=0.67 5.26 (± 0.46) 4.70 (± 0.46) 0.56 (± 0.63) P=0.37 N=373 N=376 N=373 ADCS-ADL (±SE) - 6.27 (± 0.57) - 5.32 (± 0.57) - 0.95 (± 0.79) P=0.23 - 6.43 (± 0.57) - 5.32 (± 0.57) - 1.10 (± 0.79) P=0.16 *Based on the intent-to-treat population BID = twice daily ADAS-COG12 = The Alzheimer's Disease Assessment Scale – Cognitive Subscale (a lower number represents less cognitive impairment) ADCS-ADL = Alzheimer's Disease Cooperative Study – Activities of Daily Living (a higher number represents less functional impairment) Safety Data: The table below provides a high-level summary of the patient demographic and safety data. Simufilam continued to demonstrate an overall favorable safety profile. Metrics for Simufilam and Placebo Simufilam 100 mg BID Simufilam 50 mg BID Placebo BID Baseline* N=374 N=376 N=375 Age, mean (SD), in years 73.6 ± 8.2 74.5 ± 7.6 73.7 ± 7.9 Sex, n (%) female 208 (55.6%) 207 (55.1%) 214 (57.1%) MMSE Score (No.%,) 21-27 240 (64.2%) 242 (64.4%) 235 (62.7%) 16-20 134 (35.8%) 134 (35.6%) 138 (36.8%) Race/Ethnicity White 326 (87.2%) 326 (86.7%) 313 (83.5%) Black 17 (4.5%) 23 (6.1%) 21 (5.6%) Asian 28 (7.5%) 21 (5.6%) 32 (8.5%) Other 3 (0.8%) 6 (1.6%) 9 (2.4%) Safety** N=374 N=376 N=373 Any Adverse Event (AE) 286 (76.5%) 288 (76.6%) 282 (75.6%) Serious AEs 43 (11.5%) 61 (16.2%) 45 (12.1%) Death 2 (0.5%) 6 (1.6%) 3 (0.8%) AEs leading to discontinuation from the study 32 (8.6%) 34 (9.0%) 17 (4.6%) Most Frequent AEs ≥ 5.0% 1: COVID-19 45 (12.0%) 49 (13.0%) 40 (10.7%) 2: Urinary Tract Infection 32 (8.6%) 41 (10.9%) 34 (9.1%) 3: Fall 32 (8.6%) 43 (11.4%) 51 (13.7%) 4: Dizziness 26 (7.0%) 11 (2.9%) 23 (6.2%) 5: Diarrhea 14 (3.7%) 19 (5.1%) 15 (4.0%) *Based on the intent-to-treat population **Based on the safety population BID = twice daily AD = Alzheimer's disease MMSE = Mini-Mental State Examination About REFOCUS-ALZ REFOCUS-ALZ (NCT05026177) is a Phase 3 trial designed as a multi-center, double-blinded, placebo-controlled, randomized parallel group study to evaluate the safety and efficacy of two doses of simufilam compared to a placebo in a study involving over 75 clinical trial sites in the U.S., Canada, Puerto Rico and South Korea. The clinical trial sites that conducted REFOCUS-ALZ were completely distinct from the clinical trial sites that conducted RETHINK-ALZ. REFOCUS-ALZ randomized approximately 1,125 people utilizing the same eligibility criteria as RETHINK-ALZ. Subjects were randomized 1:1:1 to receive simufilam, dosed in 50 mg or 100 mg tablets, or a matched placebo, dosed orally twice daily (BID) for 76 weeks. On November 25, 2024, the Company announced plans to discontinue the REFOCUS-ALZ study and its intention to report topline data from that trial, including the complete 52-week dataset and a large portion of 76-week data. The prespecified co-primary endpoints for this study included the change in cognition and function from baseline to the end of the double-blind treatment period at week 76, assessed by the ADAS-COG12 and ADCS-ADL scales, comparing each dose of simufilam to placebo. Secondary endpoints included several well validated measures of neuropsychiatric symptoms and caregiver burden. Safety was evaluated by adverse event monitoring, as well as standard laboratory and ECG assessments. The study also included an evaluation of changes in plasma and cerebrospinal fluid biomarkers from baseline to week 76, including P-tau217 (phosphorylated tau at threonine 217), GFAP (glial fibrillary acidic protein) and NFL (neurofilament light chain), as well as an evaluation of various brain volumes using MRI (magnetic resonance imaging) and amyloid and tau deposition using PET (positron emission tomography) scans from baseline to week 76. About Simufilam Simufilam is a proprietary, investigational oral small molecule that targets the filamin A protein. About Cassava Sciences, Inc. Cassava Sciences, Inc. (NASDAQ: SAVA), a clinical-stage biotechnology company focused on developing novel, investigational treatments for central nervous system disorders, including Alzheimer's disease and tuberous sclerosis complex (TSC)-related epilepsy. Simufilam is a proprietary, investigational oral small molecule that targets the filamin A protein. The Company is based in Austin, Texas. For More Information Contact: Investors Sandya von der Weid Media Company Eric Schoen, Chief Financial Officer (512) 501-2450 Cautionary Note Regarding Forward-Looking Statements: This news release contains forward-looking statements that include but are not limited to statements regarding: REFOCUS-ALZ and RETHINK-ALZ, the timing for discontinuation of our Alzheimer's disease development program, our plans for the development of investigational treatments for central nervous system disorders, our plans to conduct preclinical studies of simufilam relating to seizures in TSC, the potential for simufilam as a treatment for TSC-related epilepsy, our strategic expense management efforts and the timing of anticipated milestones. These statements may be identified by words such as 'anticipate', 'before', 'believe', 'could', 'expect', 'forecast', 'intend', 'may', 'pending', 'plan', 'possible', 'potential', 'prepares for', 'will', and other words and terms of similar meaning. Such statements are based on our current expectations and projections about future events. Such statements speak only as of the date of this news release and are subject to a number of risks, uncertainties and assumptions, including, but not limited to, those risks relating to the ability to efficiently discontinue the Company's Alzheimer's disease development program, the ability to advance preclinical studies related to TSC-related epilepsy, and other risks inherent in drug discovery and development or specific to Cassava Sciences, Inc., as described in the section entitled 'Risk Factors' in our Annual Report on Form 10-K for the year ended December 31, 2024, and future reports to be filed with the SEC. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from expectations in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking statements and events discussed in this news release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, we disclaim any intention or responsibility for updating or revising any forward-looking statements. For further information regarding these and other risks related to our business, investors should consult our filings with the SEC, which are available on the SEC's website at All of our pharmaceutical assets under development are investigational product candidates. They have not been approved for use in any medical indication by any regulatory authority in any jurisdiction and their safety, efficacy or other desirable attributes, if any, have not been established in any patient population. Consequently, none of our product candidates is approved or available for sale anywhere in the world. Our clinical results from earlier-stage clinical trials may not be indicative of future results from later-stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or any scientific data we present or publish. We are in the business of new drug discovery, development and commercialization. Our research and development activities are long, complex, costly and involve a high degree of risk. Holders of our common stock should carefully read our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q in their entirety, including the risk factors therein. Because risk is fundamental to the process of drug discovery, development and commercialization, you are cautioned to not invest in our publicly traded securities unless you are prepared to sustain a total loss of the money you have invested.
Yahoo
09-02-2025
- Health
- Yahoo
How greed and profit fueled one failed Alzheimer drug
On May 3, 2021, Matt Price drove his 73-year-old father Stephen from their New Jersey home to a medical strip mall on the Jersey Shore, for his first injection of an experimental drug called simufilam. Cassava Sciences, a Texas biopharma company, had developed simufilam to treat (and possibly cure) Alzheimer's disease, the most common form of dementia that afflicts tens of millions of people worldwide. When Matt, 27, first heard about simufilam, 'it sounded exciting,' writes Charles Piller in his new book, 'Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's' (Atria/One Signal Publishers), out now. Rather than simply calming symptoms, simufilam promised 'to slow, stop, or reverse cognitive decline — or for people who have no symptoms, prevent them — by attacking Alzheimer's biochemical cause,' writes Piller. It was based on a long-debated notion called the 'amyloid hypothesis,' which argued that Alzheimer's is caused by the buildup of the protein amyloid in the brain. 'If true, its removal would lead to a cure,' writes Piller. The discovery was shocking, especially given that it'd been introduced by a small biotech company that previously specialized in opioid painkillers and 'had never taken a drug to market in its fifteen years of existence,' writes Piller. 'Yet it claimed to have discovered a new molecule that stabbed the dark heart of the terrible illness.' Even in the beginning, Matt Price, a Harvard-trained epidemiologist and global-health specialist, had his doubts. Cassava's theory, which had not yet been validated by independent researchers, 'seemed weird and a bit thin,' Matt told the author. His concerns would soon be confirmed by a whistleblower, who produced 'convincing evidence that lab studies at the heart of the dominant hypothesis for the cause of Alzheimer's disease might have been based on bogus data,' writes Piller. The amyloid hypothesis wasn't just wrong, but it took valuable resources away from other promising theories on how to treat Alzheimer's. It was just the latest example, writes Piller, 'of the exaggeration, hype, and sheer fakery and fraud that has characterized Alzheimer's research for decades.' And it's not a problem confined to Alzheimer's research alone. As of this month, at least 55,000 medical and scholarly studies have been retracted, according to the Retraction Watch database from the Center of Scientific Integrity. And it's estimated that there may be as many as several hundred thousand fake studies still circulating and not yet identified. Even when they are exposed, journals are often slow to retract the bogus studies, if it happens at all. It's not just an issue of wasted research dollars. 'It makes people start to distrust the clinical research enterprise,' says Price. Simufilam began as an experimental drug — code-named PTI-125 — developed by neuroscientists Lindsay Burns and Hoau-Yan Wang. It was designed to target filamin A, which becomes twisted into an abnormal shape and causes inflammation in the brain, promoting the formation of myloid-beta proteins. PTI-125, the researchers suggested, could reverse those terrible effects. The drug was renamed simufilam in August of 2020, and in preliminary studies, patients started showing improvement after just a month — 'extraordinary for any Alzheimer's trial,' writes Piller. Simufilam began to seem like the holy grail, 'the dream drug that generations of researchers had searched for in vain,' the author writes. By late July 2021, the tiny biopharma company, whose sample size for their simufilam experiments was a minuscule fifty participants, suddenly had a market valuation of $5.4 billion. The victory was short-lived. On Aug. 18, 2021, just weeks after the company's stock reached record highs, two neuroscientists — Geoffrey Pitt of Weill Cornell Medical College and David Bredt, a former executive at drugmakers Eli Lilly and Johnson & Johnson — submitted a 'citizen petition' to the FDA, asking them to take a closer look at simufilam. Their main concern was that the drug's development 'contained manipulated scientific images,' writes Piller. 'In short, they asserted, the work looked like it had been doctored.' To help prove their suspicions, they brought in Matthew Schrag, a neurologist and neuroscientist at Vanderbilt University, who would become 'the most important whistleblower in the history of Alzheimer's,' writes Piller. When they asked for Schrag's help, 'my response was, 'You think I'm stupid enough to do that?' ' Schrag told the author. 'Apparently, I was.' Using ImageJ and MIPAV, software developed and endorsed by the NIH, Schrag carefully studied the images used in the simufilam study. He had a 'seasoned eye for detecting digital manipulation with common software programs,' writes Piller. Almost immediately, he spotted proof of manipulation. 'Schrag saw micrographs — magnifications of microscopic features of brain tissue — that seemed obviously cloned,' writes Piller. 'Yet they were presented as findings for different experimental conditions.' Schrag worried that he wasn't just uncovering evidence of research misconduct, but something much larger and more ominous. 'How had those problems gone unnoticed for years or even decades?' Piller writes. '[Schrag] wondered nervously: What other Alzheimer's research should be reconsidered with skeptical eyes?' Schrag had an uphill battle, mostly because 'disproving someone else's experiment can be a death wish in science,' writes Piller. Or as Schrag explained to the author, 'The field is absolutely calibrated to the newest, most interesting, most cutting-edge discovery. It disincentivizes replication at every turn.' Piller shared Schrag's findings with over a dozen experts, including several top Alzheimer's researchers. While most were hesitant to go on the record saying anything negative about the original research, some — like Donna Wilcock, an Alzheimer's expert at the University of Kentucky who would later become editor of Alzheimer's & Dementia — admitted that several images showed 'shockingly blatant' signs of tampering. But others, like Dennis Selkoe, a Harvard professor of neurologic diseases and a celebrated Alzheimer's researcher, 'chastised' the author for his criticism of the 'objective evidence' that reducing amyloid in the human brain produces better cognitive outcomes. 'I'm on the right side of history,' argued Selkoe, who Piller accuses of being part of the 'Amyloid Mafia.' George Perry, a scientist at the University of Texas at San Antonio and editor of the Journal of Alzheimer's Disease, agreed with Piller that many Alzheimer's researchers are too hellbent on being correct. 'The major goal of these people is to win—if it isn't the Nobel Prize, it's God's glory,' Perry told the author. 'To be acknowledged that they really did something great. They don't want the amyloid hypothesis to die, because then they have no legacy.' Schrag delivered his Cassava dossier to the NIH in 2021, providing 'forensic street cred' to doubts about the research, writes Piller. Two years later, in 2023, a university panel found Hoau-Yan guilty of 'egregious misconduct' because of his work for Cassava. Last September, the company agreed to pay $40 million to the Securities and Exchange Commission (SEC) for misleading investors. And then in November, Cassava acknowledged that simufilam failed to deliver the results they'd expected in a phase 3 clinical trial, and the company would be discontinuing research. Their stock plummeted by more than 80% after the announcement. Schrag wasn't surprised by the outcome. 'You can cheat to get a paper,' he told the author. 'You can cheat to get a degree. You can cheat to get a grant. You can't cheat to cure a disease. Biology doesn't care.'
