Oral ALZ-801 Found to Improve Memory in Alzheimer’s Patients
Treatment with Alzheon‘s oral candidate ALZ-801 (valiltramiprosate) lowered levels of a key biomarker for Alzheimer’s disease — and led to significant memory improvements in people with the neurodegenerative disorder.
That’s according to data from a six-month interim analysis of an ongoing Phase 2 biomarker trial (NCT04693520) evaluating the potential therapy.
The trial is assessing the safety and efficacy of daily oral treatment with ALZ-801 in people with early Alzheimer’s who have either one or two copies of a certain genetic variant associated with disease progression.
The findings showed that ALZ-801 reduced the levels of p-tau 181, an Alzheimer’s biomarker for disease progression in patients with that variant.
“These data and ongoing studies position ALZ-801 to potentially become the first oral agent that can slow or even stop and prevent Alzheimer’s pathology [disease development] in patients and healthy individuals at risk for the disease,” Susan Abushakra, MD, Alzheon‘s chief medical officer, said in a company press release.
New trial findings for ALZ-801
Abushakra discussed the findings in an oral presentation at the Alzheimer’s Association International Conference (AAIC), being held in San Diego, California, July 31 to Aug 4. Her presentation was titled “Effects of Oral ALZ-801, an Amyloid Oligomer Inhibitor, on Plasma Biomarkers in APOE4 Carriers with Early Alzheimer’s Disease: Results of Six-month Interim Analysis from a Phase 2 Biomarker Study,”
In her talk, Abushakra also reviewed the development strategy and path toward regulatory approval for ALZ-801. There were updates from the Phase 2 study, and from APOLLOE4, a Phase 3 trial (NCT04770220) involving early Alzheimer’s patients.
ALZ-801 is an oral anti-oligomer agent, which aims to block the formation of the toxic amyloid-beta protein that accumulates in the brains of Alzheimer’s patients. These clumps have been shown to contribute to cognitive declines.
According to Alzheon, the therapy was shown to inhibit amyloid formation at the dose now being used in Phase 3 testing.
The therapy was given fast track designation by the U.S. Food and Drug Administration to speed its development toward regulatory review.
In clinical trials, ALZ-801 is being tested in Alzheimer’s patients who have one or two copies of a particular genetic variant in the apolipoprotein E gene, known as APOE. The variant, called APOE4, is linked to the risk of developing Alzheimer’s, and also to more rapid disease progression after diagnosis.
It is estimated that the 65-70% of Alzheimer’s patients with one or two APOE4 copies — who show a particularly high brain burden of amyloid buildup — may stand to benefit most from an anti-amyloid therapy like ALZ-801.
The Phase 2 biomarker study is evaluating the safety and efficacy of daily oral ALZ-801 tablets (256 mg), administered once daily for two weeks and twice daily thereafter. The fully enrolled trial, being conducted at sites in the Czech Republic and the Netherlands, includes 84 people with Alzheimer’s who have either one or two copies of APOE4.
Its main goal is to evaluate changes in levels of disease biomarkers in the blood and cerebrospinal fluid — the liquid surrounding the brain and spinal cord — over about two years. MRI biomarkers and cognitive function also are being assessed.
Now, the six-month interim data suggest the treatment is effective, according to Alzheon.
Lower biomarker levels found
Treated patients exhibit significantly reduced levels of p-tau181, a biomarker of disease progression. These reductions were several-fold greater than that seen with anti-amyloid antibody treatments, Alzheon noted.
Significant improvements also were observed in memory tests over the six-month period.
“Importantly, rather than simply slowing cognitive decline as seen with other anti-amyloid agents, subjects treated with ALZ-801 showed significant memory improvement from baseline over 6 months in parallel with the p-tau181 reduction,” Abushakra said.
ALZ-801 also was safe, consistent with previously reported safety data. No evidence has been observed of vasogenic edema — a buildup of fluid surrounding the brain, leading to swelling and increased pressure in the skull — across 2,000 treated patients in clinical studies. This complication has been seen after infusions with anti-amyloid antibodies.
“Combined with a favorable safety profile and no events of vasogenic edema across the ALZ-801 studies, our new biomarker data, and promising cognitive benefits, support the disease modifying effect of ALZ-801 in Alzheimer’s patients,” Abushakra added.
APOLLOE4 is still recruiting up to 3oo early Alzheimer’s patients at nearly 1oo sites worldwide. Eligible patients will each have two copies of APOE4.
Participants are randomly selected to receive twice daily ALZ-801 (265 mg) or a placebo, over 78 weeks (nearly 1.5 years). The study’s primary efficacy goal is to assess changes in cognition and disease biomarkers.
“Alzheon has experienced tremendous progress in the past year, during which we launched the APOLLOE4 Phase 3 study, reported industry-leading disease modifying effects from our Phase 2 biomarker trial of oral ALZ-801 in Alzheimer’s patients, and initiated a collaboration to commercialize a diagnostic that can measure the toxic forms of amyloid in human brain,” said Martin Tolar, MD, PhD, founder, president and CEO of Alzheon.
Tolar noted that this progress placed the company in a strong financial position to complete these trials, which may lead to a submission for regulatory approval of ALZ-801.
The Phase 2 biomarker study is expected to conclude in 2023 and APOLLOE4 is expected to conclude in 2024.