Feixiong Cheng, PhD

"We need to focus on clinical data homogenization. There are many different health care systems and hospitals that use different criteria and end points to validate the diagnosis of AD. This makes our clinical trial design very challenging.”

The use of repurposed drugs within the Alzheimer disease (AD) clinical pipeline has become an increasingly attractive route for development in recent years. There are several reasons why a particular drug might be chosen, most of which are related to its specific mechanism of action and potential to be effective in targeting a single aspect of the brain, such as an anti-inflammatory agent, for example.

One such drug, sildenafil (Revatio), demonstrated its promise as a candidate for prevention and treatment of patients with AD in a long-term study presented at the 

2021 Alzheimer’s Association International Conference (AAIC)

, July 26-30. Lead author Feixiong Cheng, PhD, and colleagues found that use of the 

drug was significantly associated with a 69% reduced risk

 of AD compared with matched non-sildenafil users (HR, 0.31 [95% CI, 0.25-0.39];

<1 x 10-8). Despite the positive results of this study, Cheng claims there are still aspects of the disease which make it challenging to utilize repurposed drugs.

, notes that there remain inconsistencies with the way clinical trials are designed and which outcomes are used, making it much hard to gauge the clinical benefit of these treatments. He sat down with 

to discuss these issues, and what needs to be addressed to ease the process of researching repurposed drugs in AD.

Cheng F, Fang J, Zhang P, et al. Sildenafil reduces the incidence of Alzheimer’s disease. Presented at 2021 AAIC Annual Meeting; July 26-29. Abstract 254

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The assistant professor at Cleveland Clinic provided thoughts on the barriers clinicians face when formulating and conducting Alzheimer disease clinical trials with repurposed drugs. 

Greatest Challenges in Repurposing Alzheimer Drugs: Feixiong Cheng, PhD

"Another challenge I must mention is that we have to think of the drug within a precision medicine study setting. It’s not to just repurpose the drug for all patients with Alzheimer disease. This drug may only have efficacy in one specific individual.”

, July 26-30, research presented by Feixiong Cheng, PhD, identified sildenafil (Revatio) as a promising drug candidate for the prevention and treatment of Alzheimer disease (AD). Using a developed endophenotype molecular network-based methodology, the investigators conducted 5 comparison analyses, which included other drugs such as diltiazem (Cardizem; Valeant), losartan (Cozaar; Merck), glimepiride (Amaryl; Hoechst) and metformin (Glucophage; Merck).

All told, the data showed a statistically significantly 69% reduced risk of AD for sildenafil users compared to matched non-sildenafil usage. In recent years, the AD research field has had an increase in the number of repurposed agents within the clinical pipeline. While there are several promising FDA-approved drugs in circulation, choosing the correct option to test in a clinical trial setting requires careful examination, according to Cheng.

, Cheng discussed what goes into deciding what drugs may be good candidates for AD, and which mechanistic actions researchers should key in on. He also stressed that being able to validate a given drug’s efficacy is crucial in understanding whether its right to spend time and resources on it.

The assistant professor at Cleveland Clinic discussed key factors to consider when choosing repurposed drugs that could show max potential in treating Alzheimer disease. 

Feixiong Cheng, PhD

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