FRAMINGHAM, Mass. — Alzheon, Inc., a clinical-stage biopharmaceutical company developing novel therapies and diagnostics for Alzheimer’s disease and other neurodegenerative disorders, announced the peer-reviewed publication of results from its pivotal Phase 3 APOLLOE4 trial of oral valiltramiprosate (ALZ-801) in APOE4/4 homozygous individuals with early Alzheimer’s disease. The study, titled “Clinical Efficacy, Safety and Imaging Effects of Oral Valiltramiprosate in APOEε4/ε4 Homozygotes with Early Alzheimer’s Disease: Results of Phase 3, Randomized, Double-Blind, Placebo-Controlled, 78-Week APOLLOE4 Trial,” appears in the journal Drugs and is available online at Springer.
Valiltramiprosate is an investigational oral therapy designed to inhibit the formation of neurotoxic soluble amyloid oligomers, acting upstream in the amyloid cascade. The APOLLOE4 trial—the first Phase 3 study dedicated exclusively to APOE4/4 patients with symptomatic Alzheimer’s—enrolled 325 participants across North America and Europe with mild cognitive impairment (MCI) or mild Alzheimer’s dementia.
While the study did not achieve statistical significance in the overall population, prespecified subgroup analyses demonstrated nominally significant and clinically meaningful cognitive and functional benefits in patients at the MCI stage. These findings were accompanied by imaging data showing a significant slowing of brain atrophy and reduced water diffusivity, both consistent with neuroprotection.
“Despite progress in approved Alzheimer’s therapies, there remains a major unmet need for treatments with improved safety, efficacy, and access,” said Susan Abushakra, M.D., Chief Medical Officer of Alzheon. “The APOLLOE4 data show meaningful cognitive and functional benefits in MCI patients, along with strong evidence of neuroprotection and brain preservation. This represents an important step forward for the field and for a population that remains underserved.”
Importantly, valiltramiprosate was associated with a favorable safety profile and no increased risk of amyloid-related imaging abnormalities (ARIA), including vasogenic brain edema or microhemorrhages. No symptomatic ARIA was observed among treated patients, distinguishing the therapy from currently approved anti-amyloid antibodies, which carry higher safety risks—especially for APOE4/4 individuals, who represent about 15 percent of Alzheimer’s cases worldwide.
“APOLLOE4 is the largest clinical trial ever conducted in symptomatic APOE4/4 patients,” said Aidan Power, M.B., B.Ch., M.R.C.Psych., Chief Development Officer of Alzheon. “The results reinforce valiltramiprosate’s potential to become the first oral therapy capable of slowing Alzheimer’s pathology in genetically high-risk patients, with a safety profile that may allow broader access and earlier intervention.”
Marwan Sabbagh, M.D., FAAN, an investigator in the APOLLOE4 trial, added, “The slowing of brain atrophy across multiple regions, combined with cognitive and functional improvements in MCI patients, provides compelling evidence of neuroprotection. Just as importantly, the absence of vasogenic edema makes valiltramiprosate a promising and safer oral alternative for APOE4/4 patients.”
The 78-week, randomized, double-blind, placebo-controlled APOLLOE4 study enrolled patients aged 50–80 with early symptomatic Alzheimer’s disease, defined as MCI or mild dementia. Participants were randomized to receive either placebo or 265 mg of ALZ-801 twice daily. The trial included a diverse patient population, with intentional recruitment from underrepresented groups in the United States, and uniquely allowed inclusion of patients with existing microbleeds and siderosis lesions—reflecting real-world disease characteristics.
According to Alzheon, the findings support valiltramiprosate’s continued development as a potential first-in-class oral disease-modifying therapy capable of slowing Alzheimer’s pathology safely and effectively in patients carrying two copies of the APOE4 gene.
