Cassava Sciences stock craters after Alzheimer’s drug trial flops in critical phase

Cassava Sciences, Inc., a clinical-stage biotechnology company, revealed a significant setback in its pursuit of an effective treatment for Alzheimer’s disease. The company reported that its Phase 3 ReThink-ALZ trial for simufilam, a promising investigational oral drug, failed to meet its co-primary, secondary, and exploratory biomarker endpoints. This news has sent shockwaves through the biotech industry, leading to a dramatic 84% plunge in Cassava Sciences’ stock value.

The ReThink-ALZ trial was designed to evaluate simufilam’s safety and efficacy in patients with mild to moderate Alzheimer’s disease. Over 800 participants across the United States, Canada, and Australia took part in the double-blinded, placebo-controlled study. The primary focus was on changes in cognition and daily functioning, measured by the ADAS-Cog12 and ADCS-ADL scales, respectively. Unfortunately, the results showed no significant improvement compared to the placebo group, effectively dashing hopes for this experimental treatment.

CEO reflects on trial results and next steps

Rick Barry, Chief Executive Officer of Cassava Sciences, expressed deep disappointment over the outcome, particularly for patients and families living with Alzheimer’s disease. Barry noted that the cognitive decline observed in the placebo group was less pronounced than in earlier trials, prompting further analysis to understand these discrepancies. While maintaining simufilam’s favorable safety profile, Barry admitted that the results have major implications for the company’s second Phase 3 trial, ReFocus-ALZ.

As a result, Cassava Sciences has made the difficult decision to discontinue ReFocus-ALZ as well as an open-label extension study. The company plans to release a detailed analysis of the trial data at future medical conferences to contribute to ongoing research in Alzheimer’s treatments. Barry expressed gratitude to the patients, caregivers, and investigators who contributed to the study, acknowledging the immense effort involved in conducting the trials.

Study design and its challenges

The ReThink-ALZ trial was conducted under a Special Protocol Assessment with the U.S. Food and Drug Administration, lending credibility to its rigorous design. Participants were randomized to receive either simufilam or a placebo for 52 weeks, with secondary measures assessing neuropsychiatric symptoms and caregiver burden. A pharmacokinetic and plasma biomarker sub-study was also included, evaluating approximately 100 subjects at multiple time points. Despite these efforts, the data did not align with the promising preclinical findings that initially generated optimism around simufilam.

Financial and industry impact

The failure of the ReThink-ALZ trial has had an immediate and profound impact on Cassava Sciences’ market performance. The stock’s 84% decline underscores investor concerns about the company’s ability to recover from this setback. This blow comes on the heels of previous controversies, including allegations of data manipulation in earlier trials, which Cassava Sciences resolved with a $40 million settlement.

As of September 30, 2024, the company reported $149 million in cash reserves, which may offer some runway for future initiatives. However, the loss of simufilam as a viable candidate significantly narrows Cassava Sciences’ development pipeline.

Future of Alzheimer’s research

While the results are disappointing, they highlight the immense challenges of developing treatments for Alzheimer’s disease. Experts in the field suggest that the data collected during the trials could still provide valuable insights into the complex pathology of the disease. Cassava Sciences’ decision to analyze and share these findings demonstrates a commitment to advancing Alzheimer’s research, even in the face of adversity.

This latest development underscores the unpredictable nature of drug development, particularly for neurodegenerative diseases. The biotech industry will undoubtedly watch closely as Cassava Sciences evaluates its next steps, hoping the lessons learned from this trial can pave the way for future breakthroughs.