Cassava Sciences Announces Positive Results In Phase 2 Trial Of New Alzheimer’s Drug

Losing a loved one to Alzheimer’s disease is a scary and painful process, one that many Americans know all too well. Yet despite the fact that more than 5 million Americans are living with Alzheimer’s disease, relatively little is known on how to treat and prevent this degenerative condition. 

On Monday September 14th, biotech company Cassava Sciences announced that the company’s Alzheimer’s drug, sumifilam, showed positive results in treating Alzheimer’s patients in a phase 2 study. The data will be presented at H.C. Wainwright’s 22nd Annual Global Investment Conference.  

“We feel that this is a drug that finally can offer some real hope to patients who have Alzheimer’s, as well as people who have a family history of Alzheimer’s,” says Cassava Sciences founder and CEO Remi Barbier. “Up until now, there really has been very very little hope for these patients.” 

Cassava’s phase 2 study showed that among 64 patients, those treated with sumifilam showed improvements in multiple disease-indicating biomarkers and cognition tests compared to patients treated with a placebo. Patients treated with 100mg of sumifilam showed an 18% decrease in total tau levels and a 14% increase in amyloid beta42 (in Alzheimer’s disease, tau levels are high and amyloid beta42 is low). The patients treated with sumifilam also showed improvements in memory tests, though these results were not statistically significant. 

Alzheimer’s disease is a neurological disease that causes progressive cell death in the brain, leading to confusion and memory loss. Though it can affect people of any age, it is most common in older adults, and one in ten people over the age of 65 have Alzheimer’s dementia. The disease disproportionately affects women, Black and Hispanic communities, and can eventually be fatal. Despite it being the sixth-leading cause of death in the United States, why some people get the disease and whether or not it can be cured is still a mystery. 

What we do know is that two proteins found in the brain, beta-amyloid and tau, are found in abnormal levels in the brains of people with Alzheimer’s disease. Both proteins can be toxic, and form clumps and tangles that disrupt cell function in the brain. The majority of Alzheimer’s drugs approved and being researched today target beta-amyloid or tau, and try to cleanse the brain of these toxic protein build-ups. But this doesn’t get at the root of the disease, since we still don’t know why and how these proteins go haywire in some people but not others. "All of the approved drugs don't really treat the underlying disease,” says Adam Boxer, an Alzheimer’s researcher and the director of UCSF’s Neuroscience Clinical Research Unit, “they just help the brain work more efficiently." Boxer was not involved in Cassava’s research study. 

Sumifilam works by targeting filamin A, a protein that, when altered, may influence the toxic proteins that cause Alzheimer’s disease. "Amyloid disrupts the protein tau, and in order to do that it requires an accomplice protein: filamin A," says Lindsay Burns, the lead scientist on Cassava’s Alzheimer’s disease program. If you put filamin A back in its normal form it won’t let amyloid mess up tau, she says. 

The focus on filamin A makes Cassava’s approach distinctly different from most other life sciences companies. “I think the most developed drugs or treatment programs are still focused on amyloid proteins and tau proteins,” Boxer says, “but there are increasingly other approaches that are being investigated.” Biogen, one of the leaders in the race for a new Alzheimer’s drug, received FDA priority review for its drug aducanumab last month, which targets amyloid proteins and could be approved as early as Q1 2021.  

The Austin-based Cassava Sciences was founded in 1998 and hasn’t yet brought a drug to market. It has a market cap of $83 million and it's only drug candidate right now is sumifilam, meaning there is significant pressure on the success of this drug. In May 2020, the company encountered a hurdle when the independent lab that analyzes Cassava’s data reported that the phase 2 trial, which was funded by the National Institutes of Health, did not meet its primary endpoint. “Our hearts sank,” says CEO Barbier. But upon looking at the data more closely, “there were some really quirky things in the data,” he says, “nothing made sense.” Biomarkers that should rise and fall together moved separately, and patients in the placebo arm of the trial showed results that varied wildly. The company sent the data to a second independent lab for analysis, which found discrepancies in the first analysis and reported positive findings in the phase 2 trial. 

The trial still has limitations though. For one, the drug was only tested in 64 patients over a period of 28 days. Alzheimer’s disease can be extremely slow-moving, and oftentimes it can take months or years to notice a difference in symptoms. That’s the next step for Cassava Sciences: a large, phase 3 study that will be conducted over a period of multiple years. Barbier says that Cassava hopes to begin the phase 3 study by the end of 2021. 

In addition to sumifilam, Cassava Sciences is also working on developing a diagnostic test for Alzheimer’s disease. The goal is a blood draw that can pinpoint who is at risk for Alzheimer’s or who is in the early stages of developing the disease before symptoms even start. This would allow people to begin treatment early, and hopefully slow or even reverse the disease. 

Cassava Sciences isn’t the only company working on new Alzheimer’s drugs or tests. But based on their latest results, Barbier says, “I think we have a clear head-start.”