Cassava Sciences SAVA recently suffered yet another setback, which raises concern regarding its prospects.

Last week, the company announced that the phase III study REFOCUS-ALZ on lead pipeline candidate, simufilam, in mild-to-moderate Alzheimer’s disease (AD) failed to achieve the prespecified co-primary endpoints.

Simufilam is SAVA’s proprietary, investigational oral small molecule that targets the filamin A protein.

Treatment with the drug failed to achieve a significant reduction in cognitive and functional decline in AD patients when compared to placebo over 76 weeks, as assessed by the ADAS-COG12 and ADCS-ADL scales. The study also failed to meet any pre-specified secondary and exploratory biomarker endpoint.

The REFOCUS-ALZ study enrolled 1,125 AD patients, who were randomized equally to receive either a twice-daily oral dose of simufilam (50 mg or 100 mg tablets) or placebo for 76 weeks. The candidate, however, demonstrated an acceptable safety profile in the study.

In November 2024, SAVA suffered a massive setback when it reported that the candidate failed to meet the primary endpoints in the late-stage RETHINK-ALZ study, which evaluated simufilam in patients with mild-to-moderate AD.

Consequently, Cassava decided to discontinue the REFOCUS-ALZ study and dropped its intention to report top-line data from that trial. Simufilam continued to demonstrate a favorable overall safety profile.

SAVA will now discontinue all efforts to develop simufilam for AD. It expects to phase out the program by the end of the second quarter.

With the termination of this program, SAVA no longer has any late-stage candidate in its pipeline.

Nonetheless, simufilam is being evaluated for the treatment of Tuberous sclerosis complex (TSC)-related epilepsy.

The company also has an investigational diagnostic product candidate, SavaDx, in its portfolio. SavaDX is a novel biomarker assay being studied for the detection of Alzheimer’s disease from a small blood sample.

However, with only $128.6 million in cash and equivalents at the end of December 2024, it is not certain how far the company can fund its operations.  

Alzheimer’s Disease: A Challenging Market

Alzheimer's is a progressive, fatal disease of the brain characterized by a decline in memory, language and other thinking skills, as well as changes in mood and behavior.

However, developing drugs for this disease is a complex and challenging affair. Quite a few pharma and biotech players had earlier faced setbacks in developing an AD drug.

Currently, there are two drugs approved by the FDA in the AD space — Leqembi and Kisunla. Both these drugs are approved for treating early symptomatic AD, which includes mild cognitive impairment or mild dementia stage of the disease.

Japan-based Eisai markets Leqembi in partnership with the Biogen BIIB. Kisunla was developed by Eli Lilly LLY and was approved by the FDA last year.

Eli Lilly and Biogen/Eisai drugs are based on similar mechanisms, which reduce the accumulation of amyloid beta (Aβ) plaques in the brain. Aβ is a protein that is said to be the primary cause of the cognitive decline associated with Alzheimer’s disease.

 

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