Exenatide - the drug that failed

Hopes of a Parkinson's breakthrough dashed but no clarity yet on reasons for failure.

For the Parkinson’s community this has been a difficult week. A drug that held great promise as possibly the first to slow down the progression of Parkinson’s has fallen at the final hurdle, a phase 3 clinical trial. The drug was Exenatide, a diabetes treatment which in a phase 2 trial had shown it could deliver improvements in a participant’s condition as compared to a placebo.

But on Monday afternoon the 200 participants in the phase 3 trial were told in an online meeting that it had not been successful - that there was no significant difference in the progression of the disease between those who had been given the drug and the group given a placebo. The obvious question is why there was such a big difference between the results of the phase 2 trial and the failure at phase 3. It turns out that at this stage that simply is not known.

The problem is that, while the researchers have the overall results, they are still working on the granular detail of some of the tests carried out during the trial, for instance procedures which would show how much of the drug was getting through to the brains of participants. Without that, it is difficult to know whether the trial failed because not enough of it got to where it needed to be or because it was just not effective.

The announcement of the trial’s failure was very low key, with brief statements on the websites of Parkinson’s UK and Cure Parkinson’s. There will be far more detail given when the researchers have a paper published in The Lancet, but that could be months away, especially as medical journals hardly rush to publish a story of failure rather than success. So for now, the Parkinson’s community is in limbo, knowing the news is bad but not really clear how bad.

Neverthless, the failure is already having an impact. Exenatide was one of a group of drugs called GLP-1 agonists identified as having the potential to slow down Parkinson’s - now trials of others may struggle to get funding.

On Tuesday evening, some of the Movers and Shakers team recorded an episode of the podcast in front of a live audience of Parkinson’s golfers who were taking part in a tournament at The Belfry in Warwickshire. It was an exuberant evening where we discussed the benefits of sport for Parkies with people who seem to have quite serious symptoms - until they launch a 200 yard drive smack down the middle of the fairway. But the news about exenatide was just filtering through, and it did cast a bit of a pall over proceedings.

Charlie Appleyard of Sport Parkinson’s told the audience that the news only served to demonstrate that it was no use waiting for some wonder drug to come along - the only reliable way of slowing the disease was exercise.

So, the obvious question is why did the exenatide researchers not wait until the full results were published before saying anything? Well, given that we ran an item on Movers and Shakers a few weeks ago questioning the delay in getting information to trial participants, I am in no place to criticise them.

They were caught between a rock and a hard place, wanting to give participants who had finished their course of exenatide as long as two years ago some certainty about how it had worked, while staying within the very strict rules governing trials. Even sending out a newsletter to triallists involved going through a laborious ethics check.

What seems evident, however, is that the whole process of running clinical trials is hopelessly inefficient. The first major study in humans of exenatide took place in 2008 - 16 years later, after huge efforts by dedicated scientists funded by charities from the Michael J.Fox Foundation to Cure Parkinson’s we still await the full results.

Thankfully, something is being done to accelerate the process, with new multi-arm trials where several drugs can be trialled by the same team using the same participants. Drugs would be switched out when they failed, with new candidates brought in, rather than starting all over again building the trial infrastructure. I am. sure many Parkies will join me in saying ‘bring it on”.