Losing a loved one to Alzheimer’s disease is a frightening and painful process, one that many Americans know all too well. Yet despite the fact that more than 5 million Americans live with Alzheimer’s disease, relatively little is known about how to treat and prevent this degenerative disease.
On Monday, September 14, biotechnology company Cassava Sciences announced that its Alzheimer’s drug, sumifilam, showed positive results in treating patients with Alzheimer’s disease in a phase 2 study. data will be presented at the 22nd Annual HC Wainwright Global Investment Conference.
“We believe this is a drug that can finally offer real hope to Alzheimer’s patients, as well as people with a family history of Alzheimer’s,” says Cassava Sciences Founder and CEO, Rémi Barbier. “Until now, there was really very, very little hope for these patients.”
The phase 2 cassava study showed that among 64 patients, those treated with sumifilam showed improvements in several disease indicator biomarkers and cognitive tests compared to patients treated with placebo. Patients treated with 100 mg sumifilam experienced an 18% decrease in total tau levels and a 14% increase in beta-amyloid42 (in Alzheimer’s disease, tau levels are high and beta-amyloid42 is weak). Patients treated with sumifilam also showed improvements in memory tests, although 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. Although it can affect people of all ages, it is more common in older people, and one in ten people over the age of 65 has Alzheimer’s disease. The disease disproportionately affects women, black and Hispanic communities, and can potentially be fatal. Although it is the sixth leading cause of death in the United States, why some people contract the disease and whether or not it can be cured remains a mystery.
What we do know is that two proteins found in the brain, beta-amyloid and tau, are found at abnormal levels in the brains of people with Alzheimer’s disease. Both proteins can be toxic and form clumps and tangles that disrupt the functioning of cells in the brain. The majority of Alzheimer’s drugs approved and researched today target beta-amyloid, or tau, and attempt to cleanse the brain of these toxic protein buildups. But that doesn’t get to the root of the disease, as we still don’t know why and how these proteins go haywire in some people but not in others. “Not all approved drugs really treat the underlying disease,” says Adam Boxer, Alzheimer’s disease researcher and director of UCSF’s Clinical Neuroscience Research Unit, “they just help the brain to operate more efficiently “. Boxer was not involved in the Cassava research study.
Sumifilam works by targeting filamin A, a protein that, when changed, can influence toxic proteins that cause Alzheimer’s disease. “Amyloid disrupts the tau protein, and to do that, you need a companion protein: filamin A,” says Lindsay Burns, senior scientist in the Cassava Alzheimer’s disease program. If you put the filamin A back to its normal form, it won’t let the amyloid mess up the tau, she says.
The focus on Filamin A makes Cassava’s approach markedly different from that of most other life science companies. “I think the most developed drugs or treatment programs are still focused on amyloid proteins and tau proteins,” Boxer says, “but there are more and more other approaches that are being explored. ” Biogen, one of the leaders in the race for a new drug against Alzheimer’s disease, received priority review from the FDA last month for its drug aducanumab, which targets amyloid proteins and could be approved as early as the first trimester. 2021.
Austin-based Cassava Sciences was founded in 1998 and has yet to bring a drug to market. It has a market cap of $ 83 million and its only drug candidate at the moment is sumifilam, which means there is significant pressure on the drug’s success. In May 2020, the company hit a roadblock when the independent laboratory analyzing the cassava data reported that the Phase 2 trial, funded by the National Institutes of Health, had failed to meet its primary endpoint. “Our hearts have collapsed,” says CEO Barbier. But looking at the data more closely, “there were some really weird things in the data,” he says, “nothing made sense.” The biomarkers that should move up and down together moved separately, and patients in the placebo arm of the trial showed widely varying results. The company sent the data to a second independent lab for analysis, which found discrepancies in the first analysis and reported positive results in the Phase 2 trial.
The lawsuit still has limitations though. For one thing, the drug was only tested in 64 patients over a 28-day period. Alzheimer’s disease can progress extremely slowly, and it often takes months or years to notice a difference in symptoms. This is the next step for Cassava Sciences: a large phase 3 study that will be carried out over a period of several years. Barbier says Cassava hopes to begin the Phase 3 study by the end of 2021.
In addition to sumifilam, Cassava Sciences is also working on the development of a diagnostic test for Alzheimer’s disease. The goal is a blood test that can determine who is at risk for Alzheimer’s disease or who is in the early stages of the disease’s development even before symptoms appear. This would allow people to start treatment early and hopefully slow down or even reverse the disease.
Cassava Sciences is not the only company working on new drugs or tests for Alzheimer’s disease. But based on their latest results, Barbier says, “I think we have a head start.