Resverlogix has announced that its lead drug RVX-208, a first in class ApoA-I production drug, illustrated positive effects on an important cognitive function and Alzheimer's Disease (AD) marker, plasma Amyloid beta 40 (Aβ40). This analysis was performed based on increasing evidence in the literature that the transport of potentially harmful Aβ40 from the brain to the general circulatory system may be beneficial.
Several population studies have indicated that high HDL cholesterol is associated with protection from developing Alzheimer's Disease. It has also been shown that low plasma Aβ40 is a risk factor for developing Alzheimer's Disease in older patients. Since the Alzheimer's Disease biomarker Aβ40 bind to ApoA-I it has been hypothesized that increasing ApoA-I would transport Aβ40 out of the brain thereby decreasing the Aβ40 load in the brain, in effect having possible disease modifying effect.
To assess potential for treatment effects by RVX-208 on Alzheimer's Disease, plasma Aβ40 was analyzed before and after 12 weeks treatment in a stable coronary artery disease population, i.e. the ASSERT population of 299 patients.
In the quartile with the lowest plasma Aβ40 at baseline, which is known to be at greater risk for developing Alzheimer's Disease, at a dose of 150 mg, b.i.d., a highly significant 34.8 pg/mL change from baseline (p=0.0013) and 13.4% change compared to placebo was observed. The data further supports previous Phase I trial data and the hypothesis that RVX-208 treatment can also augment Aβ40 transport from the brain.
Dr. Jan Johansson Senior Vice President of Medical Affairs stated, "We have been building upon a hypothesis that increased Aβ40 seen in plasma illustrates movement out of the brain. We believe the augmented ApoA-I production by RVX-208, functional HDL and enhanced reverse cholesterol transport, could be transporting potentially harmful Aβ40 from the brain to plasma. This is a very important new area of neurovascular biology that we intend to pursue."
"These repeated findings will help continue to drive our efforts to further understand the complex relationship between lipoproteins, amyloid beta and the devastating disease of Alzheimer's. Further analysis and planning will take place prior to determining the next steps, however, as this drug has already passed Phase I, of the FDA review process, a future trial would likely commence as a Phase II program in Alzheimer's Disease patients," added Dr. Johansson.
Emerging evidence and data is accumulating for a protective effect of good HDL cholesterol against Alzheimer's Disease. Key findings from large epidemiology studies such as the Harvard Women's Study, the Honolulu Aging Study, the White Hall 2 study and the Manhattan Cognitive Study continue to build the relationship between increased HDL, ApoA-I and improved cognitive function and Alzheimer's outcomes.