Long-term extension studies seek to further evaluate ALZ-801 for Alzheimer’s disease

Alzheon Inc. has enrolled patients who completed either phase 2 or phase 3 trials to evaluate ALZ-801 as a treatment for early Alzheimer’s disease in long-term study extensions, according to a company-issued press release.

ALZ-801 (valiltramiprosate) is a potential first-in-class oral disease-modifying therapy that works by blocking the formation of neurotoxic soluble beta amyloid oligomers.

The ongoing ALZ-801 APOLLOE4 double-blind, randomized phase 3 trial is designed to test the safety, efficacy, biomarker and imaging effects of ALZ-801 among patients with early AD who have two copies of the 4 allele of the apolipoprotein E (APOE4) gene. The primary objective of the study is to measure the impact of ALZ-801 on cognition using the Alzheimer's Disease Assessment Scale–Cognitive Subscale.

Over 78 weeks, patients in the initial phase of the trial received a 265 mg oral dose of ALZ-801 twice daily or placebo. Topline data from the initial phase is anticipated in the second half of 2024, according to the release.

Participants who completed the full phase 3 trial and were still eligible were invited to enroll in the study extension and will be treated with ALZ-801 for an additional 52 weeks (130 weeks total). The first patient was dosed in the trial extension on April 30.

“Following the completion of the [APOLLOE4 phase 3] trial, participants who choose to continue into the long-term extension where all subjects receive active treatment, will help us evaluate long-term effects of ALZ-801/valiltramiprosate on the progression of AD, as well as generate additional safety and tolerability data,” Aidan Power, MB, MSc, MRC Psych, chief development officer of Alzheon, said in the release.

Further, Alzheon has initiated a second 52-week extension of the ALZ-801 phase 2 biomarker trial, which will now run for a total of 208 weeks, according to the release.

The phase 2 trial was initially designed as a 104-week study to evaluate the effects of ALZ-801 on cerebrospinal fluid and plasma biomarkers, which are sensitive early markers of AD progression, according to the release.

Researchers enrolled patients with early AD who tested positive for amyloid and tau biomarkers in cerebrospinal fluid and had the APOE4/4 or APOE3/4 genotype. All patients received 265 mg of oral ALZ-801 twice daily.

The initial study met its primary endpoint with a 31% reduction from baseline of plasma p-tau₁₈₁ at 104 weeks, according to the release. After implementing a prior 52-week extension last year, researchers are enrolling now patients who completed the trial and previous trial extension in another 52-week extension.

Assessments of safety, plasma biomarkers, hippocampal volume, cortical thickness and cognitive effects will be performed at key points throughout the extended phase 2 trial.

“The phase 2 biomarker trial generated compelling data demonstrating that treatment with oral ALZ-801 leads to a sustained reduction in p-tau₁₈₁, a key measure of brain neurodegeneration, as well as slowing of hippocampal atrophy compared to a matched external control arm, and stabilization of cognition for 2 years,” John Hey, PhD, chief scientific officer of Alzheon, said in the release. “Given these encouraging results, we are compelled to extend the trial for an additional year, bringing the treatment period to four years for these patients.”