Trekking along with tramiprosate

FRAMINGHAM, Mass.—November began on a positive note for Alzheon Inc. in the clinic as the company shared data from a pair of Phase 3 studies in addition to initiating further studies for tramiprosate, the biologically active agent of ALZ-801. ALZ-801, a first-in-class small-molecule inhibitor of amyloid formation and neurotoxicity, is an optimized prodrug of tramiprosate being advanced by Alzheon in symptomatic Alzheimer’s patients with apolipoprotein E4/4 (APOE4/4) genotype.

As explained by Dr. Anton P. Porsteinsson, professor of psychiatry at the University of Rochester School of Medicine and Dentistry, director of the Alzheimer’s Disease Care, Research and Education Program at the University of Rochester and an investigator in the North American Phase 3 clinical trial, “Apolipoprotein E4 carriers comprise up to 60 percent of AD patients, with APOE4/4 homozygotes representing approximately 10-15 percent of all AD patients. This genetically well-defined population has an 8- to 12-fold increased risk of developing AD as well as more rapidly progressive disease, usually becoming symptomatic a decade earlier than non-carriers of apolipoprotein E4 genotype. We also know from recent imaging studies that APOE4/4 homozygotes have the highest rate of positive amyloid scans, at approximately 90-95 percent positivity. Unfortunately, these patients are also at the highest risk of developing vasogenic edema, known as ARIA-E, with some amyloid targeted candidate drugs. This makes it imperative to develop drugs for this population that provide meaningful efficacy without a safety trade-off.”

Alzheon announced results from an analysis of two prior independent Phase 3 studies of tramiprosate in patients with Alzheimer’s disease presenting with the APOE4/4 genotype. Study participants who received tramiprosate saw significant, clinically meaningful and sustained cognitive improvement on the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog) on top of standard of care through 78 weeks. In addition, the benefit of twice-daily tramiprosate 150 mg versus placebo was both sustained and increased over time to maximal benefit of up to four points at 65 to 78 weeks. Significant efficacy trends on the functional Clinical Dementia Rating-Sum of Boxes outcome of approximately one point at 65 and 78 weeks were also seen.

The data from both the North American and European Union trials, which combined included approximately 250 APOE4/4 patients receiving twice-daily doses of either 100 mg or 150 mg of tramiprosate, showed both doses to be well tolerated with a favorable safety profile.

“These promising results from two independent datasets continue to support our accelerated development plan for ALZ-801,” Dr. Martin Tolar, founder, president and CEO of Alzheon, said in a press release. “Once we have data from the ALZ-801 multiple ascending dose study, which is underway, we will advance ALZ-801 into Phase 3 in this very targeted, genetically defined population with high medical need.”

The company also announced the beginning of two clinical studies of ALZ-801 that are expected to provide the last necessary clinical data for advancing ALZ-801 into the Phase 3 program. The first is a Phase 1b multiple dose-ranging trial that will evaluate the safety, tolerability and pharmacokinetics of oral ALZ-801 in healthy elderly volunteers, and the second is a tablet bioequivalence Phase 1b study, a solid dose formulation study evaluating the pharmacokinetics and food effect of a prototype tablet formulation with a single oral dose in healthy elderly volunteers. Both trials are expected to be completed by the first quarter of next year.

“With the robust body of existing positive clinical data in hand, we believe these studies represent the last clinical steps before we start the pivotal Phase 3 clinical study with our amyloid-targeting drug candidate ALZ-801 in Alzheimer’s disease,” commented Tolar. “Building on the existing positive results related to ALZ-801 which include the extensive clinical evidence from its active compound tramiprosate, we have designed ALZ-801 to offer a unique approach and potentially transformative treatment for patients with Alzheimer’s disease. We are excited about the prospects for ALZ-801, as we have optimized its pharmacokinetic and tolerability profile, and designed our clinical plan building on the subgroup analysis of the Phase 3 studies with tramiprosate that showed compelling efficacy results in apolipoprotein E4 positive Alzheimer’s disease subjects.”