Alzheon’s oral anti-amyloid drug has potential to be first oral Aβ-targeting therapy approved in US and EU: GlobalData

Given the complex pathophysiology of Alzheimer’s disease (AD), developing disease modifying therapies (DMTs) that target different aspects of AD pathology is critical. American clinical-stage biopharmaceutical company Alzheon has recently presented promising interim results from its Phase II Biomarker Trial (NCT04693520) of its oral, brain-penetrant, amyloid-oligomer inhibitor ALZ-801 (valiltramiprosate). Against this backdrop, ALZ-801 has the potential to be the first oral Aβ-targeting therapy to be approved in the US and EU in early AD, says GlobalData.

Erela Dana, Director of Neurology at GlobalData, comments: “Amyloid beta (Aβ)-targeting therapies hold promise, with this mechanism of action (MOA) recently seeing some success with the FDA’s approval of Biogen’s anti-Aβ monoclonal antibody (mAb) Aduhelm (aducanumab) in 2021, followed by Eisai/Biogen’s anti-Aβ mAb Leqembi (lecanemab) in January 2023.”

GlobalData forecasts that the anti-Aβ therapies will reach approximately $7.1 billion in the mild cognitive impairment (MCI) and mild AD patient populations by 2030 globally (US, France, Germany, Italy, Spain, UK, Japan, and China), with ALZ-801 accounting for approximately 10% of this market as the only oral asset to become available outside of China in an MOA dominated by mAbs.

ALZ-801 is currently in Phase III, being evaluated for the treatment of apolipoprotein E 4 (APOE4) carrier patients with early AD.

The key opinion leaders (KOLs) previously interviewed by GlobalData highlight that the ALZ-801 target population of early AD patients, who are homozygous for the APOE4 allele, represent a subgroup that has a strong unmet need for novel disease-modifying approaches.

Thus far, the results over two years of treatment with ALZ-801 have been presented of the four-year open-label biomarker study. Overall, ALZ-801 treatment demonstrated sustained improvement over two years in plasma biomarkers, hippocampal volume, and cognitive effects in the target population.

Dana comments: “There is a strong correlation between the biomarker outcomes and ALZ-801’s cognitive benefits. The presented biomarker results support the disease-modifying effects of ALZ-801 in APOE4 carriers with early AD with promising clinical efficacy and favorable safety, with no observed cases of amyloid-related imaging abnormalities related to underlying vasogenic edema (ARIA-E), a known side effect of the anti-Aβ mAbs, to date.”

Further to its Phase II biomarker study, Alzheon plans to announce the topline results of its pivotal APOLLOE4 (NCT04770220) Phase III trial in Q3 2024, with a potential NDA submission to the US FDA later this year.

Dana concludes: “Should Phase III outcomes follow the positive outcomes from the two-year Phase II biomarker data and support the hypotheses that by acting upstream of anti-Aβ mAbs, ALZ-801 could provide significantly improved amyloid clearance, it would pave the way for Alzheon to launch its AD asset in 2025 as the first oral anti-Aβ DMT in the US.”