Differences Between Two Trials Were Evaluated
The entry criteria for PHOENIX trial differed modestly from those of the CENTAUR trial. Clinically definite or probable ALS was required in only two or more body regions versus three or more in the earlier trial. Patients were also allowed entry with SVC greater than 60% versus greater than 55% for CENTAUR and have had a longer period since symptom onset (< 24 vs < 18 months). Both studies permitted use of edaravone.
When stratified, patients who entered PHOENIX with CENTAUR-like entry criteria had a similar response to PB&TURSO relative to those who did not. Similarly, there were no meaningful differences between those enrolled in European study sites versus elsewhere. Background edaravone versus no edaravone also had no apparent effect on outcomes.
An ongoing open-label extension of the PHOENIX trial is still collecting data on survival, which was a prespecified endpoint. This endpoint, which requires 70% or more of patients to have died or have been followed for 3 or more years since the last patient was randomized, is not expected until February 2026.
Although “there are further biomarker and subgroup analyses planned,” Dr. van den Berg said that the neutral results of the PHOENIX trial, which he characterized as the largest controlled trial in ALS ever conducted, do not encourage further studies with this agent.
‘Unfortunate’ Results
Robert Bowser, PhD, chief scientific officer and chair of the department of translational neuroscience, Barrow Neurological Institute, Phoenix, called the results “unfortunate.” Just last year, Dr. Bowser published a study showing a reduction in the concentration of biomarkers associated with ALS among patients in the CENTAUR study who were treated with PB&TURSO.
Moreover, the reduction in the serum concentrations of the biomarkers he studied, which included C-reactive protein and YKL-40, correlated with ALSFRS-R total score.
In that paper, he speculated that CRP and YKL-40 might emerge as treatment-sensitive biomarkers in ALS “pending further confirmatory studies, but Dr. Bowser indicated that the PHOENIX study has prompted the correct response from the manufacturers.
“Credit should be given to the leaders at Amylyx for following through with their promise to remove the drug from the market if the PHOENIX study did not confirm the results from the CENTAUR study,” he said.
However, he believes that the study will still have value for better understanding ALS.
“As we move forward, it will be interesting to see biomarker data generated from the biosamples collected during the PHOENIX trial to learn more about treatment impact on biomarkers within those that received the drug,” he said. “I am sure we will continue to learn more from the PHOENIX trial.”
Dr. van den Berg has financial relationships with approximately 10 pharmaceutical companies, including Amylyx, which provided funding for the PHOENIX trial. Dr. Bowser reported no potential conflicts of interest.