Cassava Sciences recently reported results from its second of two phase 3 studies known as REFOCUS-ALZ. This was a huge study as it recruited a total of 1,125 patients. It was noted that the co-primary endpoints of this late-stage trial were not met with statistical significance, in that the drug was no better than placebo in terms of allowing patients to see an improvement in two cognitive measures known as ADAS-COG12 and ADCS-ADL.
This was not a huge surprise, though, because back on November 25th of 2024, the company ended up discontinuing another phase 3 study, known as RETHINK-ALZ. This 52-week late-stage trial also reported that the co-primary endpoints were not met with statistical significance. At that time, the company terminated the trial on the basis of it not achieving its intended goals.
It was a long battle for this biotech to prove that simufilam could be able to help treat patients with Alzheimer’s Disease. They laid out a lot of groundwork about seeing success in prior early-stage studies in terms of biomarkers being keen, but unfortunately this didn’t translate to success in the clinic in terms of the co-primary endpoints.
Unfortunately, investors are now left holding the bag as this small-cap biotech shifts its focus to preclinical studies evaluating simufilam’s potential in being able to treat Tuberous Sclerosis Complex-related Epilepsies. While a shift in focus is the right thing to do, it remains to be seen if it can get this program into the clinic rapidly. With that being said, it could potentially be a few years before this enters the clinic, depending upon how much animal testing or preclinical work is needed to file an IND to begin phase 1 testing and beyond.
It would have been ideal if this drug worked in treating these Alzheimer’s Disease patients, because treatment options remain limited. Plus, the trial failure rate for developing a drug of this caliber remains high. With no other pipeline in place at the moment, other than preclinical work on advancing simufilam for TSC-related Epilepsies, its future is looking bleak at the moment.