Alzheon Announces Dosing of First Patient in ALZ-801 Phase 2 Biomarker Study in APOE4 Carriers with Early Alzheimer’s Disease

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  • Study to Evaluate ALZ-801 Effects on Alzheimer’s Biomarkers Associated with Clinical Benefit
  • Includes Comprehensive Biomarker Assessment to Accelerate Development of ALZ-801 for Alzheimer’s Disease Prevention
  • Facilitates Biomarker-Enabled Indication Expansion for ALZ-801 to Two-Thirds of All Alzheimer’s Patients Carrying APOE4 Gene

FRAMINGHAM, Mass.: Alzheon, Inc., a clinical-stage biopharmaceutical company focused on developing new medicines for patients suffering from Alzheimer’s disease (AD) and other neurodegenerative disorders, today announced the initiation of a Phase 2 study evaluating biomarker effects of ALZ-801, an oral treatment blocking the formation of neurotoxic soluble amyloid oligomers, in Early AD patients carrying one or two copies of the ε4 allele of the apolipoprotein E (APOE4) gene. AD patients with this genetic profile have a higher risk of rapid disease progression and are responsive to drug agents targeting pathogenic amyloid oligomers.

The primary objective of the Phase 2 biomarker study is to assess the effects of 265 mg oral tablet of ALZ-801, administered twice daily for two years, on fluid and imaging biomarkers shown to be sensitive early markers of AD progression. The biomarkers selected for this study have been shown to correlate with clinical benefit in AD patients in trials with amyloid-targeted antibody therapies. This Phase 2 study is the first AD biomarker trial to prospectively evaluate APOE4 carriers using leading-edge cerebrospinal fluid (CSF) and plasma biomarkers, as well as volumetric magnetic resonance imaging (MRI) evaluating brain atrophy. Study evaluations will include a battery of biomarkers that reflect amyloid pathology (beta-amyloid 42 and 40), tau pathology (phosphorylated tau protein, or p-tau), and neuronal injury (neurofilament light chain protein, or NfL).

A Biomarker Steering Committee comprised of world-leading AD experts advised on the design of the trial and will oversee its conduct. Committee members include Kaj Blennow, MD, Ph.D., Professor and Head of Research on Neurochemical Pathogenesis and Diagnostics at the University of Gothenburg in Sweden; Eric Reiman, MD, Ph.D., Executive Director of the Banner Alzheimer’s Institute and Clinical Director of the Neurogenomics Division at the Translational Genomics Research Institute in Phoenix, Arizona; and Philip Scheltens, MD, Professor of Cognitive Neurology and Director of the Alzheimer Center at Amsterdam University Medical Centers in the Netherlands.

“This study will provide important insights into the effects of treatment with oral ALZ-801 in APOE4 carriers, using an extensive set of cutting-edge biomarkers shown to indicate a clinically relevant benefit to patients. Positive biomarker changes would confirm disease-modifying effects of ALZ-801 anti-amyloid oligomer therapy and enable the use of plasma biomarkers, such as p-tau and NfL, as surrogate outcome measures for registration trials for ALZ-801, in particular in the prevention of Alzheimer’s disease,” said Dr. Kaj Blennow.

“Recent findings in the Alzheimer’s field have shown that soluble amyloid oligomers are directly neurotoxic upstream drivers of the disease and lead to early increases in p-tau and other markers of neuronal injury. Furthermore, APOE4 carriers have been shown to have up to three-fold higher brain levels of soluble amyloid oligomers compared to non-carriers. These factors provide a strong biological rationale for using an anti-oligomer agent, such as ALZ-801, for treatment and prevention in APOE4 carriers, who represent the majority of patients with Alzheimer’s disease,” said Dr. Philip Scheltens.

Phase 2 Biomarker Study Expands NIA-Backed ALZ-801 Pivotal Phase 3 Program

Recently, Alzheon was awarded a $47 million grant from the National Institute on Aging (NIA) to advance the Phase 3 study of ALZ-801 in high risk APOE4/4 homozygous AD patients, starting in 1Q 2021. The addition of this Phase 2 biomarker trial will provide first-ever insights into the biomarker profile of a broader population of APOE4 carriers who receive ALZ-801 treatment, and thereby expand the potential indications for ALZ-801 to approximately two-thirds of all Alzheimer’s patients.

The Phase 2 biomarker trial is designed to accelerate the development of ALZ-801 for the prevention of AD in asymptomatic individuals with risk factors, based on their genetic and biomarker profile. ALZ-801 is an oral small molecule, with a favorable safety and tolerability profile more suitable for long-term use in AD treatment and prevention than amyloid-targeted antibodies that require burdensome 1-3 hour bi-weekly or monthly intravenous infusions or subcutaneous injections, as well as MRI safety monitoring for serious adverse events such as brain edema and microbleeds.

“This biomarker study is a key element of our overall Alzheimer’s clinical development program for ALZ‑801,” said Susan Abushakra, MD, Alzheon Chief Medical Officer. “With the urgent need to advance new treatments for a broad population of Alzheimer’s patients, a positive biomarker readout will confirm the clinical effects of ALZ‑801 in APOE4 carriers. It also opens the exciting possibility of preventive treatment for Alzheimer’s, and enables expedited, biomarker-based development of ALZ‑801 as a convenient oral pill for patients.”

The Phase 2 biomarker trial will initially enroll 40 Early AD patients with one or two copies of the APOE4 gene, at leading clinical research sites in the Czech Republic and the Netherlands. All patients will receive ALZ-801 in 265 mg oral tablets twice daily for two years. Frequent fluid biomarker assessments, volumetric MRI imaging, and cognitive tests will be performed throughout the duration of the trial.


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