â€œThis phase 2b study did exactly what we wanted a phase 2 study to do, which was to establish a patient population in mild patients and also find a safe and well tolerated dose,â€ said Larry Altstiel, MD, PhD.
At AAN 2017, Larry Altstiel, MD, PhD, EVP, Chief Medical Officer, vTv Therapeutics, spoke with MD Magazine about his team’s two phase 3 studies in Alzheimer’s disease that studied a “well-established” target called the receptor for advanced glycation endproducts (RAGE).
According to Altstiel, they have a molecule called azeliragon that blocks the activity of RAGE, and thereby affect the major parts of Alzheimer’s disease pathology (amyloid, tau, and inflammation) — things that are commonly thought to be the most important parts of Alzheimer’s pathology. “We’re coming off a very successful phase 2b study wherein we studied 400 patients and we found, for mild-to-moderate AD patients, a robust effect on cognition.” After taking a deeper look in a preplanned analysis, the team found that most of the signals were emitting from mild patients – they attributed this connection with the mechanism of the drug.
“This phase 2b study did exactly what we wanted a phase 2 study to do, which was to establish a patient population in mild patients and also find a safe and well tolerated dose.”
It’s sort of tempting to think that if you intervene earlier in the disease process, you’ll have a better outcome. That’s what we’ve hypothesized, and we’ll see if the data show that we’re correct.
Altstiel said they have taken these data to the FDA, and have been granted fast-tracked designation and also special protocol assessment (SPA), which allows for real-time communication with the agency. According to Altstiel, “They basically said if you could recapitulate these data from the phase 2 study in your phase 3 studies, that would go a long way to help support an NDA.” So, now they have the 2 identical phase 3 trials (400 patients/each) randomized to one dose of the drug azeliragon and the other half randomized to placebo, and they are using the same outcome measures they used in the phase 2b study.
The first of these studies is now completely enrolled and actually will read out in March 2018. The second study is about to be completely enrolled and will read out in late 2018. The team is hoping for similar results to what they saw before.
“We’re very excited about this because our drug azeliragon in phase 2 studies seemed to slow the progression of cognitive decline (at least as measured by standard outcome measures) and also seemed to slow the decline in global clinical function. So, right now we will be the first company to read out with the drug in that disease slowing space,” concluded Altstiel.