Cassava Sciences, which spent 2022 trying to prove the integrity of its Alzheimer’s disease program, is trumpeting a phase 2 win for simufilam in an open-label study—but investors aren’t convinced.
The Texas biotech said that 47% of patients improved on a scale of Alzheimer’s progression over one year while taking simufilam, according to a Tuesday press release. The trial was an open-label safety study that included what Cassava called exploratory efficacy endpoints, featuring over 200 patients who had mild-to-moderate disease treated for a year or more.
Patients’ scores on the scale changed "minimally" over the year of treatment, which “is a highly desirable outcome in a clinical study of mild-to-moderate Alzheimer’s disease,” Cassava said. Along with the improvement noted, 23% of patients declined fewer than five points. The company also noted that patients with mild disease responded better than those with more advanced moderate disease.
Cassava also said that some patients had a reduction in dementia-related neuropsychiatric symptoms, which in Alzheimer’s include delusions, hallucinations, irritability and anxiety.
CEO Remi Barbier said the data “add strength and determination to our goal of helping people fight Alzheimer’s disease. But investors sent Cassava’s shares tumbling 22% to around $28 apiece, compared to a prior close of $36.44.
The top-line release did not, however, include any p-values, which is a measure of statistical significance commonly used for clinical trials to prove the study drug was behind the desired effect.
As for safety, Cassava reported that the drug was safe and well tolerated with no drug-related adverse events but three treatment-emergent adverse events. These included COVID-19, urinary tract infection and headache. There were 34 patient discontinuations, which Cassava chalked up to withdrawal of informed consent, adverse events and patient non-compliance.
Cassava provided a detailed explanation of the chain of custody for the clinical data, explaining that all data was entered into a database maintained by an independent, outside data management vendor. The information was then submitted to Pentara Corp., a consulting firm that analyzes clinical trial results.
The study was open label, meaning patients knew they were taking the study drug or placebo. Cassava said the data “do not constitute, and should not be interpreted as, regulatory evidence of safety or efficacy for simufilam in Alzheimer’s disease.” To meet that bar, the company said “rigorous evidence” must be collected from one or more large, randomized and placebo-controlled studies.
“The open-label design and size of this study may introduce clinical or statistical bias or may generate results that may not fully distinguish between drug effects and random variation,” Cassava said.
Cassava said the top-line summary was issued to give stakeholders a glimpse at the ongoing study. A final dataset will be disclosed later at a future medical conference or in a science publication, according to the release.
Meanwhile, Cassava is working on two phase 3 trials of simufilam that are randomized, double-blind and placebo-controlled. These studies will feature 1,750 patients with mild-to-moderate disease.
Over the past year, Cassava has fought back against allegations that the company manipulated research results for simufilam. In July, a Department of Justice criminal investigation was revealed by Reuters.