The following, rather interesting article, appeared on Alzheimer’s Society’s page.
n 22 July 2015, new trial results were announced for a drug for Alzheimer’s disease. Here, Research Communications Officer Dr Ian Le Guillou, who was in the room when the results were announced, looks back on the reaction to the news.
Last week dementia research hit the news in a big way as the largest dementia conference in the world was held in Washington DC. Capturing a large number of those headlines was the results of a clinical trial solanezumab, a drug developed by the pharmaceutical company Lilly, which showed signs of being able to treat Alzheimer’s disease. This led to a lot of media coverage with one front page headline claiming that it could ‘halt Alzheimer’s’.
There has now been a period of reflection on the findings and data presented. A GP writing in the BMJ criticised the comments from various sources describing the drug as a breakthrough and highlighted that the improvement in scores on the cognitive tests are so small that they may mean nothing at all for quality of life. Businessjournalists were also quick to note that the results were not quite as good as hoped, with the share price for Lilly dropping by three per cent after the announcement.
Part of the reason for the different interpretations of the results is the unusual trial design used in the study. This trial, known as a delayed start study, is explained in our background article but in short this was an extension to earlier trials that failed to show the drug had benefits in people with mild-to-moderate Alzheimer’s disease. The aim of this extension was to demonstrate that the drug could target the root cause of disease, the accumulation of amyloid protein in the brain, rather than only treating the symptoms as current treatments do.
This type of trial design has never been successfully used to get regulatory approval for a drug. This means that everyone is unsure of how this type of trial will be considered by regulators, such as the FDAor EMA, in the future. In a 90-minute session about the results at the conference, a panel discussed the implications for this trial design and what regulators would like to see in the evidence that is presented to them. There were cautions on the lack of an agreed threshold to determine if there had been an effect and that the complicated nature of the trial means that it could be more likely to go wrong or miss important treatment effects.
The results presented last week are not enough to approve the drug for patients. This is why Lilly are now running another trial of this drug called EXPEDITION 3 which only includes people with mild Alzheimer’s with the same delayed start design. The results from this trial are expected to be announced in 2017 and that is when we will have solid data.
The data does give us a glimpse of the potential for this drug. One important result is that people can take solanezumab for three and a half years safely, an issue that has plagued this class of drugs in previous trials. Tests for cognition showed a maintained difference between those people who had been taking the drug for three and a half years against those who had only been receiving it for the past two years.
This wouldn’t have been seen if the drug was only affecting symptoms, which suggests that the drug actually targets the disease process. However, people who took the drug still declined in memory and thinking tests, so expectations of what this drug can do should be tempered. It appears that the drug slows the progression of the disease but the trial was not designed to test for the size of the effect on symptoms, so the conclusions we can draw are limited. While the headline figures from the media said that the drug could reduce the decline in cognition by 34 per cent, this wasn’t actually shown in this study and comes from a later analysis of the original failed trials which has not been published. A drug that actually slows the progress of the disease would be a significant step as there is nothing else that can currently do this. After so many failures in trials in the last few years this fuels hope that something can be done about Alzheimer’s disease. That said, it is important to bear in mind that ‘we shouldn’t take our eyes off the prize, and the prize is large treatment effects’ as one speaker from the FDA said.
The results presented last week aren’t something to get too excited about if you’re looking to get your hands on a breakthrough drug. Even if everything goes to plan it will still be years before it would become available widely to people with Alzheimer’s. The results are significant because it gives Lilly the confidence to continue with their new solanezumab trial and it gives confidence to other researchers andcompanies that this type of drug could work for targeting the disease.