A centaur was a creature from Greek mythology which was half-man and half-horse. Despite such an unusual appearance such a combination could have its advantages.
It seems that another combination may hold promise in the future for people with ALS/MND (see our previous blog).
The CENTAUR clinical trial, which tested a combination of two compounds, has just announced follow up findings from the ‘open label phase’ of the trial.
‘Open Label’ means that everyone who has been in a trial (either taking the experimental treatment or the placebo) is invited to take the experimental treatment once they have completed the formal ‘randomised’ phase of the trial.
The CENTAUR trial originally contained 137 people, roughly split 2:1 treatment (89 patients) to placebo (48 patients) for just under 6 months. In total, 90 participants who finished the CENTAUR trial (56 in the treatment group and 34 in the placebo group) took part in the open label extension phase, with some taking AMX0035 (the experimental treatment) for up to 30 months. This follow up study provides information on the long term ‘real world’ effects of the drug, including potential unforeseen severe events.
In short, it was found that people who had originally taken the drug in the trial had an increased ‘median’ probability of survival than those originally on placebo. What this means is that the time until 50% of the participants in each group were still alive (known as median survival) was 25 months in the AMX0035 group vs 18.5 months in the original placebo group.
The new data were reported in a study titled “Long‐Term Survival of Participants in the CENTAUR Trial of Sodium Phenylbutyrate‐Taurursodiol in ALS,” published last week in the journal Muscle & Nerve.
What is AMX0035?
AMX0035 is a combination of two small molecules, tauroursodeoxycholic acid and sodium phenylbutyrate. The mixture is aimed at reducing nerve death by blocking stress signals within mitochondria — often described as the cells’ batteries — and the endoplasmic reticulum, part of the cell that maintains protein balance correctly.
In the original CENTAUR clinical trial, participants were randomly assigned to receive either AMX0035 or a placebo twice daily for 24 weeks. The results indicated that the treatment slowed patients’ functional decline when measuring ALSFRS-r, compared with a placebo. However, this headline result was tempered by inconclusive findings in all the other secondary endpoints, including changes in muscle strength, breathing, hospitalisation events, and blood biomarkers associated with disease progression.
What do these results mean?
These latest follow up results do offer some further cause for optimism, indicating that people on the treatment from the start of the trial lived longer than those who received the treatment over 6 months later in the Open Label phase. However, the Open Label study does not address some important questions.
For example, it is unclear whether the CENTAUR placebo group obtained any perceived functional benefit from the drug combination once they started receiving the treatment, as no ALSFRS-r measurements appear to have been taken during the Open Label phase. The latest study also does not report any potential survival benefits in this group, which is important, because it could be that early administration of the treatment in the course of the disease is a crucial factor.
We expect these results will generate a lot of discussion when the work is presented at this year’s Virtual International Symposium on ALS/MND. We also hope the company will push forward as quickly as possible in building further evidence to support their encouraging signal from the Phase 2 trial results, in anticipation of providing clinicians with a new treatment option and offering new hope to people with MND and their families.