A breakthrough for treating Alzheimer’s?

At the end of July, a number of media headlines were hailing a potential breakthrough in the treatment of Alzheimer’s disease. The BBC led with a cautious but optimistic “Early signs that drug ‘may delay Alzheimer’s decline’”, through the Telegraph’s “First drug to slow Alzheimer’s Disease unveiled in landmark breakthrough”, to the more personal focus of the Mirror’s “‘Alzheimer’s miracle drug has saved my life’: Trial Brit’s joy as dementia slowed by new cure”. About one in six people over the age of 80 are diagnosed with dementia, with Alzheimer’s disease being the most common cause (accounting for about two thirds of dementia cases). Any new treatment is therefore potentially very important, and something which those with the disease and their families obviously attach a great deal of significance to.

What did the media say?

The headlines reporting the breakthrough were numerous, covering most of the major international outlets (including those above and, for example, the Financial Times, Wall Street Journal, TIME, etc.). The coverage resulted from a presentation by pharmaceutical company, Eli Lilly, at the annual Alzheimer’s Association International Conference. The results, “met with cautious optimism” according to the BBC, suggested that the drug solanezumab kept brain cells alive in people with Alzheimer’s by acting against the build-up of a protein called amyloid. Amyloid accumulation creates “plaques”, and these eventually lead to the death of brain cells.

The BBC continued that solanezumab was originally thought to be a failed drug, as Eli Lilly had reported that it was ineffective against Alzheimer’s after a trial lasting a year and a half. However, since that failure, the company have re-examined the data, and when they looked at those in the very earliest stages of the disease, the drug appeared to “slow progression by around 34% during the study”. To put that in real terms, the reporting suggests that for those taking the drug, the decline they might normally have experienced over 18 months would be slowed, occurring over about 24 months instead. That may not seem like much, but for those living with Alzheimer’s, the individuals themselves and their families and friends, that extra time is perhaps immeasurably valuable.

The reason the news has been welcomed (cautiously) is that this is the first time a drug has been shown to modify the process through which the disease develops. The current drug used to treat Alzheimer’s, called Aricept, “can manage only the symptoms of dementia by helping the dying brain cells function”. It doesn’t actually stop the disease progressing however.

What did the research say?

Initially, the media reporting appeared to come from the conference presentation (or at least the press release accompanying it). As we’ve discussed previously at Research the Headlines, information presented at scientific meetings has rarely been through a strict peer-review process (speakers are usually selected based on a short summary of their results). That’s not to say the results are necessarily problematic, but they wouldn’t be available to those in the research community to fully scrutinise. However, a research paper reporting these new results was released simultaneously in the journal Alzheimer’s and Dementia: Translational Research and Clinical Interventions.

Led by Hong Liu-Seifert at Eli Lilly, the study reports the details of the new findings. After the initial trial which failed to show a benefit over 18 months, about 1300 people in the earliest stages of the disease were considered in greater detail. Those who had been on the drug in this group did appear to be performing better in terms of their cognitive function than those who hadn’t been receiving the drug (the placebo group). The researchers decided to follow this early-stage Alzheimer’s group for another two years, but now, all those initially on the placebo were started on the drug too. The study reported that those receiving the drug late (that is, after 18 months of having been in the placebo group) never “caught up” to the levels of functioning of those who had already been taking it for 18 months. The argument was then that the drug wasn’t simply masking symptoms, but rather it was acting on the disease process, and therefore the earlier it was given and the longer it was taken for, the better.

When analysing study data, we have to be cautious of finding results only in specific groups within our overall sample. In this case, there might be a very good reason to focus on those in the earliest stages. Those in the later stage of the disease may already have too great a burden of amyloid plaques for the drug to be effective against, for example. Given the subgroup analysis tough, it’s particularly important that these results are replicated. Eli Lilly are working on that study, and it’s likely other research groups will too base their research on these findings.

The bottom line

Of course, the story has focussed on the potential for this drug but only in those in the earliest stages of the disease. If further research supports that and the drug is successful but needs to given early, then it means that “new drugs will require earlier diagnosis of Alzheimer’s”, quoting the Guardian’s headline.

The BBC report further caveats the headlines, noting that while exciting, it is still too early to herald this as a major change in the way we treat people with Alzheimer’s: “The limited data which has been released is the scientific equivalent of a poll before a general election or a trailer ahead of a movie. It provides captivating clues, hints and teases, but nothing definitive. At the moment there is no medication that can slow down dementia. If such a drug was developed it could transform how the disease is managed.”

While that may seem pessimistic, the piece finishes with the note of optimism seen throughout the coverage: “In a field that has been plagued by repeated disappointment, even a hint of such a drug is an exciting moment.”

So, for now we wait until the next round of research is concluded, and as the Guardian cautions, even then it would require regulatory approval before being offered to patients. That said, after 10 years of failed drug trials, when “99.6% of drugs studies aimed at preventing, curing or improving Alzheimer’s symptoms were either halted or discontinued”, it’s probably OK to see this if not as a breakthrough, then perhaps the start of a breakthrough.

To be continued…

Liu-Seifert, H. et al. (2015). Delayed-start analysis: Mild Alzheimer’s disease patients in solanezumab trials, 3.5 years. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. DOI:10.1016/j.trci.2015.06.006