Second Shot at Alzheimer's Proves Unsuccessful for vTv Therapeutics' Azeliragon

Cognition Alzheimer's

vTv Therapeutics, based in High Point, North Carolina, announced that its Phase II Elevage study of azeliragon in mild Alzheimer’s disease and type 2 diabetes failed to hit its primary objective. The goal was to show improvement in cognition on the 14-item Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-cog14) compared to placebo.

In April 2018, azeliragon failed to hit either co-primary efficacy endpoint in its Phase III STEADFAST clinical trial in mild Alzheimer’s disease. The trial was made up of two independent, but identical double-blind, placebo-controlled trials, Part A and B. The group in Part A that received azeliragon demonstrated a 4.4-point decline from baseline in the ADAS-cog and a 1.6-point decline from baseline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) compared to declines in the placebo groups of 3.3 and 1.6, respectively. They were not clinically significant changes.

But in a subgroup analysis, they found something promising and decided to launch a new trial in mild Alzheimer’s and type 2 diabetes patients, which is the six-month Elevage study. However, as today’s news indicates, that didn’t work either.

“We will continue to analyze the data to determine if there are potential benefits or future applications for azeliragon in Alzheimer’s, dementia or related indications that we or other interested parties may seek to pursue,” said Steve Holcombe, vTv’s chief executive officer. “On behalf of vTv Therapeutics, we would like to extend our most sincere and heartfelt gratitude to study participants, their families, physicians and caregivers for their commitment to this important study despite the challenging circumstances created by the COVID-19 pandemic.”

Azeliragon is an orally active small-molecule antagonist of advanced glycation endproducts (RAGE). RAGE is an immunoglobulin supergene family member that is expressed on multiple brain cell types, specifically on endothelial cells and microglia, which is upregulated in Alzheimer’s disease. RAGE is believed to contribute to Alzheimer’s by promoting vascular leakage, promoting the influx of peripheral beta-amyloid into the brain, mediating beta-amyloid induced oxidative stress, and other mechanisms related to tau proteins and beta-amyloid mediated neuron death.

Yesterday the company announced it had inked a licensing deal with Anteris Bio for global rights to vTv’s novel clinical-stage Nrf2 activator compound, HPP971. Anteris Bio is a newly formed portfolio company of Aditum Bio. Aditum Bio was co-founded in 2019 by former Novartis chief executive officer Joe Jimenez and former president of the Novartis Institutes for BioMedical Research (INIBR), Mark Fishman, and is a biotech investment firm.

Anteris Bio will develop HPP971 for renal disease. The drug is vTv’s most advanced oral, small molecule activator of the Nrf2 pathway. It has wrapped two Phase I studies so far.

Under the terms of the deal, Anteris is paying vTv $2 million up front and vTv is eligible for up to $151 million in future development, regulatory and commercial sales milestones in addition to royalties on annual net sales of low double-digits. vTv also picked up a minority equity interest in Anteris Bio.

Holcombe said, “The Nrf2 pathway is a promising, novel target for combating many diseases related to oxidative stress, including renal disease. We’re thrilled to partner with Anteris to further the development of HPP971. With a focus in renal disease and a strategic partnership with TrialSpark, they will have the ability to efficiently develop HPP971 to ultimately bring a potential new treatment option to patients suffering from kidney disease.”

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