Outcome
AMX0035 was initially approved for use in the United States and Canada, based on the data from the phase 2 trial. As AMX0035 was going through the regulatory process, a phase 3 trial was underway to provide additional evidence on the benefit it may have for people with MND. Unfortunately, the phase 3 trial did not meet its primary or secondary endpoints, suggesting it is not beneficial for people with MND. The drug has since been removed from the market.
What is the drug thought to do in the body?
AMX0035, also known as ALBRIOZA in Canada and RELYVRIO in the United States, is a combination therapy, made up of two compounds– TUDCA (tauroursodeoxycholic acid) and sodium phenylbutyrate (PB). TUDCA is thought to increase the threshold for cell death by blocking key cell death pathways. While PB reduces the stress on the endoplasmic reticulum (ER), which in vital in producing proteins. This dual approach was hoped to improve the survival of neurones.
Clinical Trials
CENTAUR
The Phase 2 trial (CENTAUR) investigated the safety and efficacy of AMX0035 in 137 participants, who had been diagnosed with MND within 8 months of enrolling and the disease was rapidly progressing, over 24 weeks. After completing this trial, all participants were given the option to enter an open-label extension (OLE) study and receive the experimental treatment for an additional 30 months. You can read more about the trial here.
The study met its primary endpoint of slowing disease progression, measured by the ALS Functional Rating Scale (ALSFRS-R) MND symptoms still progressed in both groups indicated by the fall in ALSFRS-R in both groups. The average fall in the ALSFRS-R score was -1.24 points per month for the treatment and -1.66 points per month with placebo. You can read more in a publication.
Results from the open-label extension of the trial demonstrated that those who were treated with AMX0035 earlier and for longer, lived an average of 6.5 months longer than those who received it later in the open-label extension. You can read about these results here.
AMX0035 was initially approved for use in the United States and Canada based on the data from the CENTAUR trial. However, AMX0035 has since been taken off the market due to the negative results from the PHOENIX trial.
PHOENIX
The phase 3 trial (PHOENIX) investigated the safety and efficacy of AMX0035 in 664 participants, whose symptoms began within 24 months of enrolling, over 48 weeks. The trial was randomized, double-blind and placebo-controlled. The trial did not meet its primary or secondary endpoints. There was no significant difference in the change in ALSFRS-R (from baseline to 48-weeks) for those who received the treatment compared to those who received the placebo (dummy drug). There was also no difference found in secondary endpoints, such as quality of life and muscle function measurements, between those who got AMX0035 compared to those on placebo. This data suggests that AMX0035 is not beneficial for people with MND. You can read more in a press release or read about the trial here.
Latest News
2024
April 2024 - Amylyx announced they are withdrawing AMX0035 from the market in the US and Canada. You can read more in a press release.
March 2024- Topline data shows the Phase 3 PHOENIX trial did not meet its primary or secondary endpoints. There was no significant change in ALSFRS-R score for those on AMX0035 compared to those on placebo (dummy drug). You can read more about this in a press release.
2023
October 2023 - The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) have confirmed their initial negative opinion for the conditional approval of AMX0035 (Albrioza). This is the result of a re-examination of the application following a negative opinion that was announced in June. The CHMP panel reviews the scientific evidence and forms an opinion on whether new drugs should be approved in Europe. The committee based their review on data from the phase 2 CENTAUR trial. You can read more in a press release.
June 2023 - The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has announced a negative opinion for the conditional approval of AMX0035 (Albrioza). Amylyx have announced they will request a re-examination which will take approximately 4 months. You can read more here.
May 2023 - Amylyx provided an update on the regulatory approval process in Europe. They have been informed by the European Medicines Agency (EMA) that the Committee for Medicinal Products for Human Use (CHMP) is trending toward a negative opinion on the application for conditional marketing authorisation of AMX0035. A formal opinion will be made a the next CHMP meeting held June 19-22. You can read more in a press release.
February 2023 - Amylyx announce the trial has finished recruiting. Top-line results are expected in 2024.
2022
September 2022 - The FDA announced the approval of AMX0035 in the United States, as RELYVRIO™. You can find out more about this approval in a press release.
September 2022 - FDA Advisory Committee vote for the approval of AMX0035 as a treatment for MND in the United States. You can read more here.
August 2022 - The date for the second Advisory Committee has been set for 7 September 2022. You can read more here.
July 2022- The FDA announced they are planning to reconvene the Advisory Committee to discuss the approval of AMX0035. You can read more here.
July 2022 - PHOENIX opened for recruitment in the UK. You can find out more about the trial on this page or on Amylyx's website. Please contact the trial sites for availability.
June 2022 - Health Canada approved AMX0035 (ALBRIOZA) for the treatment of ALS in Canada. This approval is subject to conditions, including being dependent on safety and efficacy data from the ongoing Phase 3 PHOENIX trial. You can read more here.
May 2022 - Further data was published suggesting that the risk of events such as, trachestomy, permanent ventilation and hospitalisation was reduced by 47% for those on the trial who were originally randomised to the AMX0035 group. You can read more here.
May 2022 - Further survival data was published. You can read more here.
March 2022 - FDA Advisory Committee vote against the approval of AMX0035 as a treatment for MND in the United States. You can read more here.
Feb 2022 - Amylyx announced that the FDA Advisory Committee Meeting to review the New Drug Application for AMX0035 is scheduled for March 30, 2022. You can read more here.
Jan 2022 - Amylyx submitted a Market Authorization Application (MAA) to the European Medical Agency for AMX0035. You can read more here.
2021
December 2021 - The FDA announced it had accepted AMX0035 for priority review. You can read more here.
October 2021 - Participant recruitment for PHOENIX started in US and parts of Europe.
September 2021 - FDA announced they would consider the approval AMX0035 without a further trial.
Resources
The Scientific Advisory Council (SAC) Briefing Notes
The Scientific Advisory Council for the International Alliance of ALS/MND societies consists of 9 members from USA, UK (including MND Association's Head of Research - Dr Nick Cole), Sweden, Italy, South Africa, China, Australia and Canada.
They produce briefing notes as a trusted source of information about current experimental treatments in clinical development, such as AMX0035.
These notes are produced after many rounds of careful discussion between the SAC members.
You can find the briefing note for AMX0035 here.
Last updated: 21/08/2024