Food and Drug Administration (FDA) approves AMX0035 (Amylyx) for the American market

During a meeting of the FDA’S Peripheral and Central Nervous System Drugs Advisory Committee (PCNSDAC) on Thursday September 29 2022, the Amylyx drug AMX0035 received approval under the name RELYVRIO (AMX0035). This means that Relyvrio is available for American citizens. What does this approval mean and how does this affect patients in Europe?

AMX0035 is still being investigated in Europe in a phase 3 trial called Phoenix. This trial is necessary because the existing trial results for AMX0035 do not provide the level of evidence required by the European regulatory authorities that AMX0035 is an effective treatment for ALS (MND).

Difference between a phase 2 and phase 3 study

A phase 2 and a phase 3 study differ from each other in the number of participants and the duration of treatment. The more participants and the longer the treatment, the better the evidence about the effect and safety of the drug. In the past many phase 2 studies have suggested a benefit but when the larger phase 3 study has been done the benefit seemed to disappear. The results from the phase 2 study therefore turned out to be ‘false positive’. Normally, the FDA and EMA make decisions based on the results of a phase 3 study. Amylyx submitted a request to the FDA and EMA to make a decision on early admission to the US market based on the results from the completed phase 2 study. This decision was postponed by the FDA earlier this year but has now been approved at its September meeting. The same request for early admission to the European market is currently under consideration by the EMA. AMX0035 can only be admitted to the European market if the EMA gives a positive assessment.

What does this mean for people living with ALS in Europe?

People living with ALS will wonder whether they can also gain access to the drug through the US market. AMX0035 can only be prescribed through an attending physician in America. We do not know yet whether the American insurance companies will pay for this drug. In countries where AMX0035 is not approved currently, doctors cannot prescribe the drug. In most countries, the costs of treatment with AMX0035 will not be met by the government or insurance companies.

The Phoenix trial in Europe

The results from the current phase 3 study are needed to ensure that the drug AMX0035 has a definite positive effect on those living with ALS. If the EMA surprised the community and did not wait for the Phoenix results but instead approved AMX0035 on the phase 2 data from Centaur, this would not mean AMX0035 would be automatically available in Europe. To be available heath systems and insurers must review the trial data and decide whether they will pay for AMX0035 for their population of patients. Without the high quality phase 3 data being collected in Phoenix it is likely that many will not agree to pay for AMX0035.

More information about the Phoenix study and the contact details of participating TRICALS centers, can be found on our website.

How does AMX0035 work?

AMX0035 is a combination of two agents: sodium phenylbutyrate and taurursodiol (TUDCA) and is administered orally by dissolving the agent in a glass of water. The active substances in AMX0035 enhance each other’s influence on the energy factories of the body, the mitochondria, and reduce oxygen damage in cells. These are important clues that play a role in the pathogenic processes in ALS. By intervening on this, AMX0035 tries to reduce the loss of motor nerves and thus preserve more function. The available results from the phase 2 study show that a possible disease-retarding effect can be seen in participants. This slowing effect was measured with the ALSFRS-R, but was not apparent when measuring other outcomes such as muscle strength or lung function. In addition, the number of participants in the phase 2 study was still limited and the results from that study may also be due to chance. As a result, the data from the phase 2 remains controversial and the ongoing phase 3 study is necessary. The phase 3 Phoenix study examines whether the previously measured effects can really be attributed to the drug and determines the long-term safety of AMX0035.

Statement of the TRICALS Executive Board

While it seems to be unfair that patients in the US will most likely be able to have access to AMX0035, while those in Europe can only access the drug as part of a clinical trial, we from TRICALS believe that there is a very good scientific reason to complete the trial in Europe. We do not know for definite that AMX0035 works, as the US study was limited in time and patient numbers. If all countries took the approach the FDA have taken, we would not be able to ever effectively establish if a treatment is really effective for people with ALS.

We in TRICALS remain committed to providing the most effective therapies for all people suffering from this devastating disease as soon as possible. We will continue to conduct high quality studies that provide definitive results regarding benefits to people living with ALS of therapies.