vTv Therapeutics is recruiting patients for a large Phase 3 study, known as STEADFAST, assessing the drug azeliragon as a potential treatment for mild Alzheimer’s disease (AD). Study participants will be randomly assigned to take either a 5 mg pill containing azeliragon once a day, or a placebo (sugar pill), for 18 months, with the drug’s effectiveness determined through cognitive tests.
Azeliragon is a small inhibitory molecule that blocks a receptor called RAGE (receptor of advanced glycation endproducts), which is thought to contribute to amyloid plaque deposits in the brain. Amyloid is a protein that, along with hyperphosphorylated tau, is believed to cause Alzheimer’s brain cell death and the associated symptoms of AD. There are no current approved medications for AD that target amyloid.
While a Phase 2b study of azeliragon conducted in 399 people with mild-to-moderate Alzheimer’s was stopped prematurely for an apparent failure to show benefits (particularly its 20 mg arm), the company reported in a follow-up analysis a statistically significant improvement in cognitive measures (ADAS-Cog scores) and significantly lower rate of psychiatric events like anxiety in patients treated with azeliragon at 5 mg versus placebo for 18 months. The greatest improvements in two cognitive measures — ADAS-Cog scores and clinical dementia ratings (CDR) — were seen in those with mild disease treated at 5 mg. The 18 months of treatment given allowed for this follow-up analysis, and these results were determined by regulatory agencies to merit a larger and more advanced study, using the 5 mg dose.
Preclinical studies in mice also showed a decrease of amyloid in the brain and improvement in tests of behavior and memory ability.
Requirements for participation in the STEADFAST study include a diagnosis of “probable” AD with documented evidence that the disease has progressed. The diagnosis needs to be based both on brain imaging through MRI and standard tests for cognitive problems. The trial will not include people who have an additional neurological or psychiatric illness, cancer, or high blood pressure.
“We are excited to reach this next significant milestone in the development of azeliragon as a potential therapy to slow the decline of cognition and function in patients with Alzheimer’s disease by enrolling our first patients in our phase 3 trial,” Steve Holcombe, president and CEO of vTv, said in a press release. “There remains a critical need for the development of new treatments for this devastating disease. Azeliragon’s novel mechanism allows for targeting a receptor we believe is involved in multiple pathologic processes leading to the development and progression of Alzheimer’s disease.”