Cassava Sciences, Inc. (NASDAQ:SAVA, "Cassava", the "Company"))), a clinical-stage biotechnology company focused on developing a novel, investigational treatment for Alzheimer's disease (AD) dementia, today announced that the topline results from the Phase 3 ReThink-ALZ study of simufilam in mild-to-moderate AD did not meet each of the pre-specified 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 52, assessed by the ADAS-COG12 and ADCS-ADL scales, comparing simufilam to placebo. Simufilam continued to demonstrate an overall favorable safety profile. The Company will hold a webcast today at 8 AM ET.
"The results are disappointing for patients and their families who are living with this disease and physicians who have been looking for novel treatment options. We took careful measures to enroll patients with mild-to-moderate AD. Despite that, the loss of cognition in the placebo group was less pronounced than was previously reported in other placebo-controlled studies in AD. We are working to understand this better," said Rick Barry, President and Chief Executive Officer. "A result like this has implications on our second Phase 3 trial, ReFocus-ALZ. We have made the difficult decision to discontinue ReFocus-ALZ, given the nature of today's reported results. The complete 52-week dataset will be available from the study along with a large portion of 76-week data. We intend to report detailed analyses of both studies in the future. We will also be discontinuing the Open Label Extension study."
Mr. Barry continued, "We have a special gratitude for the patients and their families and caregivers who participated in our clinical program for AD. We are also immensely grateful to our employees, study investigators and site coordinators, as well as our other partners, for their commitment to this program. We hope the information we have gathered can ultimately be used to benefit ongoing research in AD."
The table below provides a high-level summary of the co-primary endpoints data. Topline analysis of the mild and moderate sub-groups, likewise, did not demonstrate statistical significance at week 52.
|
Co-Primary Endpoint Data* |
Simufilam 100 mg BID N= 403 |
Placebo BID N=401 |
Delta | P-value |
|
Co-Primary Endpoints LS means change from baseline to the end of the double-blind treatment period | ||||
| ADAS-COG12 (SE) | 2.8 ( 0.36) | 3.2 ( 0.36) | -0.39 ( 0.50) | P=0.43 |
| ADCS-ADL (SE) | -3.3 ( 0.44) | -3.8 ( 0.44) | 0.51 ( 0.61) | P=0.40 |
| *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) | ||||
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 | Placebo BID |
| Baseline* | ||
| Age, mean (SD), in years | 73.7 7.9 | 74.3 7.6 |
| Sex, n (%) female | 225 (55.8%) | 222 (55.4%) |
| MMSE Score (No.%,) | ||
| 21-27 | 244 (60.5%) | 250 (62.3%) |
| 16-20 | 155 (38.5%) | 146 (36.4%) |
| Race/Ethnicity | ||
| White | 366 (90.8%) | 376 (93.8%) |
| Black | 20 (5.0%) | 18 (4.5%) |
| Asian | 8 (2.0%) | 2 (0.5%) |
| Other | 9 (2.2%) | 5 (1.0%) |
| Safety** | ||
| Any Adverse Event (AE) | 284 (71.2%) | 269 (67.6%) |
| Serious AEs | 52 (13.0%) | 36 (9.0%) |
| Death | 1 (0.3%) | 3 (0.8%) |
| AEs leading to discontinuation from the study | 26 (6.5%) | 17 (4.3%) |
| Most Frequent AEs | ||
| 1: COVID-19 | 32 (8.0%) | 36 (9.0%) |
| 2: Urinary Tract Infection | 31 (7.8%) | 29 (7.3%) |
| 3: Fall | 30 (7.5%) | 30 (7.5%) |
| 4: Dizziness | 21 (5.3%) | 1 (0.3%) |
| 5: Headache | 18 (4.5%) | 11 (2.8%) |
| *Based on the intent-to-treat population **Based on the safety population BID = twice daily AD = Alzheimer's disease MMSE = Mini-Mental State Examination | ||
Cassava will continue to review all of the data and evaluate next steps. We plan to share the detailed results at a future medical meeting.
Eric Schoen, Chief Financial Officer at Cassava commented, "We remain focused on the interests of Cassava shareholders and are committed to enhancing shareholder value. Cassava is well-capitalized with approximately $149.0 million in cash and cash equivalents as of the end of the third quarter of 2024."
