Nilvadipine Slowed Cognitive Decline in Early- but not Late-Stage Alzheimer Disease in Clinical Trial Post Hoc Analysis
New data from a clinical NILVAD trial (NCT02017340) of nilvadipine (Alzforum, Archer Pharmaceuticals, Sarasota, FL) Alzheimer disease (AD) using nilvadipine identified that individuals with very mild AD show less cognitive decline over an 18-month period. On the key clinical measure of memory, those with early stage AD who took nilvadipine performed better than those who took placebo. For individuals with mild AD, the use of language was better preserved after nilvadipine treatment. In overall measures of mental ability in individuals with very early stage AD treated with nilvadipine there was a nearly 50% reduction in the rate of decline compared with those taking placebo. Nilvadipine has been previously been used to treat hypertension in many European countries and Japan, although it is not approved in the US. The new analysis was a follow up of data collected by a European network of collaborators with the Roskamp Institute scientists.
However, scientists strongly cautioned that the study also showed that the drug was not helpful, and may have even increased cognitive decline, in individuals who began the treatment much later in the disease process. "Understanding how this drug may be beneficial in very early stage patients is obviously important for further development of new treatments for AD," says Dr. Michael Mullan, executive director of the Roskamp Institute. The Institute's scientists have been awarded National Institutes of Health funding to develop second-generation drugs designed to replicate the potential beneficial effects of nilvadipine without some of the unwanted side effects such as unnecessary lowering of blood pressure. Dr. Mullan added, "the development of drugs for AD has been fraught with multiple late-stage clinical failures, but one area of consensus which has emerged is that for effectiveness of many experimental drugs the treatment must start very early in the disease process. I believe we are seeing the same effect with this treatment, and we must endeavor to increase both the potency and early use of such medicines."
In other studies, the Roskamp Institute's researchers have shown that nilvadipine can lower the levels of brain amyloid and tau in mouse models, which is consistent with current theories of the pathogenesis of AD. These findings are also consistent with the human clinical trial which suggested that the improved mental functioning was associated with increased release of toxic amyloid out of the brain.
Dr. Rudolph Tanzi, a professor of Neurology at Harvard Medical School who is familiar with the results commented, "The possibility that nilvadipine may impact the 3 main pathologies of AD (amyloid, tau, and neuroinflammation) makes it potentially very useful among current therapies. While more trials are needed, the hope is this drug will ultimately be effective for both presymptomatic prevention and treating early-stage patients."