On October 10, 2023, Arsla welcomed the arrival of the AMX0035 treatment in France. “We can announce today that, as of October 2023, patients suffering from Charcot disease may be eligible to receive treatment with AMX0035 (Relyvrio in the USA, Albrioza in Canada)”, the association wrote at the time for ALS research in a press release. `
Charcot disease and AMX0035 treatment: what are we talking about?
Charcot disease (which is rather called Amyotrophic Lateral Sclerosis or ALS, in medical jargon) is a serious neurological disease that affects motor neurons scattered in the cerebral cortex and all along the anterior part of the spinal cord. It causes paralysis that can affect all parts of the body: the limbs, the pharynx and the respiratory muscles. The initial expression is variable and the diagnosis is only made after 10 to 12 months of wandering on average.
Intended to slow the progression of the disease, treatment with AMX0035 is produced by Amylyx Pharmaceuticals laboratories. It combines 2 molecules (sodium phenylbutitrate and ursodoxicoltaurine), each already used in indications other than ALS. “Sodium phenybutyrate is a histone deacetylase inhibitor to reduce the mechanism of ‘endoplasmic reticulum stress (ER stress)’ which may contribute to motor neuron degeneration”, specifies Arsla. “Ursodoxicoltaurine (TUDCA or TURSO) is believed to reduce mitochondrial stress and allow cells to produce the energy necessary for their survival,” she adds.
The treatment is provided in the form of individual sachets (each containing 3 g of sodium phenylbutyrate and 1 g of ursodoxicoltaurine) to be reconstituted in 250 ml of water at room temperature and taken orally or through a feeding tube into the hour following preparation. The recommended dose is one sachet per day for the first three weeks and one sachet twice daily thereafter.
Charcot disease and AMX0035 treatment: 48 weeks of negative tests
As Charcot’s disease currently has no curative treatment, AMX0035 aroused great hope. But last March, it was a cold shower for patients and doctors.
“The Amylyx laboratory published a press release on March 8, 2024 indicating that the results of the PHOENIX phase 3 study (NCT05021536) for the AMX0035 molecule (or Relyvrio) proposed in the treatment of ALS are negative”, explains Professor Claude Desnuelle, vice-president of Arsla. “Contrary to what was observed in the phase 2 CENTAUR study (NCT03127514), monitoring of the ALSFRS-R functional scale score, the main efficacy criterion evaluating the progressive speed of the disease, does not show on the cohort of 630 patients studied after 48 weeks of treatment of statistically significant reduction for the treated group compared to the placebo group”, he laments. “This phase 3 study nevertheless confirms the good tolerance of the drug”, he specifies.
“Over the past 20 years, more than 50 different molecules have been tested as treatments for ALS. In almost 10% of cases, phase 2 studies were positive before phase 3 invalidated the results. “, continues the specialist.
“This announcement dampens the hopes that had emerged for a new treatment usable in ALS, to such an extent that the molecule was marketed in North America and accessible in France for several months on a restricted basis through a compassionate access procedure. “indicates Professor Claude Desnuelle. “For the moment, no press release has been made regarding the future of these accesses. Additional information must be given by the laboratory on the complete analyzes of the study during June. To date, in France, the conditions of access to the derogation procedure remains unchanged”, he finishes.
