Potential Treatment, ALZ-801, Shows Efficacy in Early Alzheimer’s Patients with Risk Gene

Joana Fernandes, PhD avatar

by Joana Fernandes, PhD |

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ALZ-801 presentation

ALZ-801 may be a safe and effective treatment for Alzheimer’s patients with mild disease who carry two copies of the APOE4/4 gene, results of a clinical program indicate.

The results are being disclosed in four presentations by the drug’s developer, Alzheon, at the 13th International Conference on Alzheimer’s and Parkinson’s Disease, taking place March 29–April 2 in Vienna.

ALZ-801 and its active molecule, tramiprosate, are designed to inhibit the toxic aggregation and accumulation of beta-amyloid plaque between nerve cells, a hallmark of Alzheimer’s disease, to protect neurons.

“We are pioneering a precision medicine approach to Alzheimer’s disease with our pivotal program for ALZ-801, by focusing on a well-recognized, genetically defined subset of Alzheimer’s patients with the APOE4 [gene] and by targeting patients at an early point in their disease progression, who have shown the greatest response to our lead molecule,” Martin Tolar, MD, PhD, and Alzheon’s founder, president, and CEO, said in a news release.

One presentation, “ALZ-801 Brain Penetration, PK/PD Analyses And Clinical Dose Projection Form Basis For Confirmatory Phase 3 Study In Alzheimer’s Disease,” showed that in Phase 1b studies with healthy elderly volunteers, ALZ-801 (265 mg tablet, twice-daily) had an improved rate of drug response and elimination from the body. Compared to previous studies of oral tramiprosate, ALZ-801 was associated with fewer gastrointestinal side effects (such as nausea and vomiting).

Alzheon also presented new data on the effect of tramiprosate in a subset of patients from Phase 3 studies that involved more than 2,000 people. This group of mild Alzheimer’s patients had two copies of the gene APOE4/4 (homozygous patients), a known genetic risk factor for Alzheimer’s. The presentation, “Tramiprosate Efficacy In APOE4 Homozygous Subjects With AD: Larger Effects In Mild Versus Moderate Patients,” showed that tramiprosate improved cognitive and functional abilities in these patients.

A third presentation is set for April 2, “Persistent Efficacy Of Tramiprosate In APOE4 Homozygous AD Subjects Treated Over 130 Weeks: Results Of North American Extension Study,” which will show that prolonged tramiprosate treatment (up to 130 weeks, 150 mg daily) allowed for sustained cognitive and functional improvement in patients. Its safety profile was favorable, with no new adverse effects.

A fourth was delivered by Dr. Martin Tolar and titled, “ALZ-801: Efficient Alzheimer’s Disease Modification by Preventing Formation of Toxic Amyloid Aggregates.” This oral presentation was part of a forum on “translational research in drug discovery” for Alzheimer’s.

“Our latest clinical analyses suggest that tramiprosate efficacy is highest in APOE4/4 homozygous [Alzheimer’s] patients at the Mild stage of disease, which is consistent with the findings from studies with other amyloid-targeted therapies,” said Susan Abushakra, chief medical officer at Alzheon. “The potential for tramiprosate efficacy to be sustained over 130 weeks is also very encouraging.”

“These analyses have informed the selection criteria for the upcoming study of ALZ-801 in homozygous patients,” she added. “With these promising efficacy data, the favorable long-term safety profile of tramiprosate, and the improved gastrointestinal tolerability of ALZ-801, we are poised to initiate the pivotal program with ALZ-801.”