Patiently Awaiting the Results of Clinical Trials for the Next Generation Alzheimer’s Disease Drugs
The International Conference on Alzheimer’s disease (ICAD) will be held in Chicago on July 26-31. Generally regarded as the premiere forum for the discussion of new treatments for AD, this conference will bring together more than 5,000 international Alzheimer’s disease experts from 60 countries to discuss topics ranging from genetics, to neuroimaging for early detection and diagnosis, to present and future therapies. The conference is held every other year and is sponsored by the Alzheimer’s Association (http://www.alz.org/icad/).
Among the most anticipated events of this conference is the presentation of the results of clinical trials for new treatments for Alzheimer’s disease. Closely watched this year are the upcoming results of two trials for drugs that are being evaluated for their ability to slow the progression of the disease. As I discussed in my last blog (Combining Medications to Successfully Treat Alzheimer’s Disease), current treatments can help with the symptoms of AD including memory loss, decline in function, and changes in mood and behavior, but they do not affect on the underlying cause of the disease. These closely watched trials for disease modifying drugs are important because this class of drugs is aimed at slowing and perhaps eventually halting the loss of brain cells and in doing so slowing the progression of the disease.
The two drugs most closely watched are Flurizan (Myriad pharmaceuticals) and bapineuzumab (‘The Alzheimer’s Disease vaccine,” Elan and Wyeth pharmaceuticals). Myriad will announce the results of a phase III clinical trial on Flurizan. Depending upon the results of this trial, the FDA may consider Flurizan for approval. Elan will announce the results of a phase II trial that should provide a preview of the results of the ongoing phase III trial with Bapineuzumab.
Elan issued a press release earlier this month that previewed the data they will present at ICAD. The press release indicated that there was significant benefit for Alzheimer’s disease patients who had been vaccinated compared to patients who were given a placebo, but importantly only for patients who carried a particular variety of a specific gene. The gene is ApoE (apolipoprotein). Individuals can have one of three versions of the gene: ApoE2, ApoE3 or ApoE4. ApoE4 is relatively rare overall, but common in patients with Alzheimer’s disease. Being ApoE4 positive (ApoE4+) increases the risk for getting Alzheimer’s disease. But this does not mean people with the gene will get the disease. Individuals who are ApoE4 negative (ApoE4-) that is, they are ApoE2 or ApoE3, have less risk of getting the disease.
In the Elan vaccine study, patients who were ApoE4- appear to have benefitted from the vaccine. Patients who were ApoE4+ did not show this benefit. Importantly, because of the way these data were analyzed, these findings must be treated as interesting, and perhaps even encouraging, but preliminary. We will have to await the results of the much larger phase III study that is now ongoing to determine just how beneficial the vaccine will be in slowing the progression of Alzheimer’s disease.
Myriad published the results of their phase II study in The Lancet in late April. Flurizan (tarenflurbil) is a SALA (selective amyloid lowering agent) that is hypothesized to reduce the formation of brain-cell destroying beta amyloid plaques. The results of the study indicated that patients on Flurizan did better on some, but not all, measures of the progression of Alzheimer’s disease. Moreover, the benefit was apparent only in patients who started the medication while in the early stages of the disease. Based upon these finding, Myriad is now testing Flurizan in a larger phase III study that is limited to patients with very mild disease. It is these data that will be presented at ICAD. If the results of this study are positive, it is possible that Flurizan could be the first drug approved by the FDA for treatment of disease progression in AD.
I will report back on the findings and implications of both the vaccine study and the Flurizan study when I return from ICAD at the end of July.