Recently, we have been made aware of the results of two Phase III trials testing if Relyvrio (AMX0035) or TUDCA provide benefit for MND patients. AMX0035, made by Amylyx, is an oral drug combining two compounds called sodium phenylbutyrate (PB) and tauroursodeoxycholic acid (TUDCA).
Unfortunately both trials showed no benefit for MND patients which has been incredibly disappointing for the whole MND community.
AMX0035 was tested in a Phase 2/3 clinical trial called CENTAUR from 2017-2019. The trial showed promising results and, based on these outcomes, the company applied to the US FDA for approval to market the drug. It is very unusual for a company to apply for approval based on Phase II data. After a somewhat contentious review process (although with strong community support), in September 2023 the FDA approved AMX0035 as RELYVRIO, based on the results of the Phase 2/3 trial and additional analyses from an open label extension. Health Canada had also conditionally approved AMX0035 (called ALBRIOZA in Canada) in June 2022 (the conditions required a successful Phase 3 trial outcome to maintain approval).
In parallel to the drug approval application, Amylyx launched a 48-week Phase 3 clinical trial called PHOENIX in 2021. This large 600 patient trial was undertaken in the US and Europe and incorporated survival as well as ALSFRS-R outcomes over a 12-month period. Amylyx stated from the outset that if the Phase 3 PHOENIX trial failed, they would withdraw Relyvrio from the market.
Given the news that the PHOENIX trial has failed, Amylyx have now announced they will be withdrawing Relyvrio from the US and Canadian markets. They have stated they will be providing the drug free-of-charge to patients in the US and Canada wishing to keep taking the drug but have not indicated how long this will continue.
We commend Amylyx for consideration of the MND community in making these extremely difficult decisions. Although there are not many treatment options for MND patients, it is critical that those we have are based on strong data and a robust approval process. We recognise this will be a massive financial hit for the company but they have placed the wellbeing of the community over their own business.
TUDCA, one of the main components of Relyvrio (AMX0035), was also tested in a separate Phase 3 trial in Europe. The trial ran over 18 months. The results showed the trial did not meet its primary aim, a reduction in MND progression measured by ALSFRS-R, as well as no significant differences across secondary aims.
These disappointing outcomes very much support the case for maintaining robust comprehensive processes for testing and approving treatments. Although the initial approval of Relyvrio was met with great excitement, this was based on insufficiently strong data and powerful advocacy from patient organisations in the US. In future, we strongly believe that treatment approvals need to be based on fully powered phase 3 trials.
Although not officially available in Australia, we understand patients may have been sourcing Relyvrio or the different components, TUDCA and sodium phenylbutyrate, privately. Our understanding is that the drugs remain safe with no serious safety issues identified from the trials of either Relyvrio or TUDCA. Our advice is to talk to your neurologist about treatment options going forward.
