What does the drug do?
AMX0035, also known as ALBRIOZA in Canada and RELYVRIO in the US, 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). This dual approach is hoped to improve the survival of neurones.
Phase 3 - PHOENIX
Amylyx announced the forthcoming 48-week, randomized placebo-controlled Phase 3 clinical trial called PHOENIX in May 2021. The Phase 3 trial (PHOENIX) to evaluate the safety and efficacy of AMX0035 in 600 participants across 55 sites in the US and Europe, Australia & UK opened for recruitment in November 2021. This phase 3 trial looks at a large cohort of participants, over 12 months. You can find out more about this trial here.
How can I take part in the trial?
The trial is now no longer recruiting.
Previous Clinical Trials
The Phase 2/3 trial (CENTAUR) to evaluate the safety and efficacy of AMX0035 in 137 participants is completed. AMX0035 was investigated in a double-blind Phase 2/3 safety and efficacy trial in 137 ALS patients diagnosed within 8 months of enrolling and with rapidly progressive disease. At 25 clinical sites across the U.S., patients were randomly assigned to either AMX0035 or placebo, given twice daily for six months. The trial was randomized, double-blind and placebo-controlled, and participants were assessed over a 24-week period for both safety and potential effect of AMX0035 on disease progression. 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. About 90% of patients, around 120 people, opted to enter in CENTAUR-OLE. You can find out more about this completed trial here.
As published in the New England Journal of Medicine (NEJM), the study met its primary efficacy endpoint of slowing ALS progression as measured by the ALS Functional Rating Scale-Revised (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. This equated to a difference of 2.32 points at the end of the 6-month study which represents a relatively small slowing of disease symptoms.
Further results of CENTAUR-OLE were published in Muscle & Nerve, which demonstrated that individuals initially treated with AMX0035 lived an average of 6.5 months longer than those originally on placebo
The publication further indicates that the effects were seen in addition to those provided by riluzole and edaravone use, though a better understanding of this additive value observation will benefit from further study. While the treatment was considered reasonably safe and tolerable, the publication also outlines that early gastrointestinal adverse events were notable and will need monitoring in future use.
An academic editorial that comments on the trial is also available here. It outlines a cautious approach to interpreting the data while balancing that these results are indeed promising. The key points of the editorial are as follows:
- Well-designed, multi-center trial with “tantalizing preliminary data”
- Trial was enriched for individuals with more rapidly progressive disease, making interpretation difficult for the wider population of people living with ALS/MND
- Secondary outcome measures were not convincingly aligned with the effect on ALSFRS-R
- Recommendation to proceed to a confirmatory phase 3 trial with wider eligibility criteria
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.
Feb 2023 - Amylyx announce the trial has finished recruiting. Top-line results are expected in 2024.
Sept 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.
Sept 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.
Dec 2021 - The FDA announced it had accepted AMX0035 for priority review. You can read more here.
Oct 2021 - Participant recruitment for PHOENIX started in US and parts of Europe.
Sept 2021 - FDA announced they would consider the approval AMX0035 without a further trial.
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: 23/06/2023