Research & Development
Amylyx Pharmaceuticals Provides Update on Ongoing Regulatory Review of AMX0035 for the Treatment of ALS in the European Union
31 May 2023 - - US-based Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) has released an update on the ongoing review of its Marketing Authorisation Application for AMX0035 (sodium phenylbutyrate and ursodoxicoltaurine [also known as taurursodiol]) for the treatment of adults with amyotrophic lateral sclerosis by the Committee for Medicinal Products for Human Use of the European Medicines Agency, the company said.

Following an oral explanation held at the May meeting of the CHMP, Amylyx was informed that the CHMP is trending toward a negative opinion on the application for conditional marketing authorisation of AMX0035.

The CHMP is expected to adopt a formal opinion on the MAA at its next meeting, which will be held June 19-22, 2023. If a negative opinion is received in June, the company intends to request a formal re-examination of the opinion, which is an approximately four-month process.

The MAA for AMX0035 is based on data from the CENTAUR clinical trial, a randomized, multicenter, placebo-controlled trial in participants with ALS (n=137), which were the basis of the full approval received from the US Food and Drug Administration and approval with conditions by Health Canada.

The trial met its prespecified primary outcome and AMX0035 is the first ALS therapy to demonstrate, in the same trial, both a statistically significant benefit in function, as well as an observed benefit on survival in a longer-term post hoc analysis.

The CENTAUR data were published in the peer-reviewed medical journals the New England Journal of Medicine, Muscle & Nerve, and the Journal of Neurology, Neurosurgery, and Psychiatry.

AMX0035 demonstrated a generally well-tolerated safety profile in the CENTAUR trial, with similar reported rates of adverse events and discontinuations in AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency in the AMX0035 group.

ALS affects approximately 29,000 people in the US and more than 30,000 people are estimated to be living with ALS in Europe (European Union and United Kingdom). In the first six months following FDA approval in the US, as of March 31, 2023, there were roughly 3,000 people actively taking RELYVRIO in the US.

RELYVRIO, an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (known as ursodoxicoltaurine outside of the US), is approved to treat amyotrophic lateral sclerosis in adults in the US and approved with conditions as ALBRIOZA for the treatment of ALS in Canada.

Additionally, the European Medicines Agency is reviewing the company's Marketing Authorisation Application for AMX0035 for the treatment of ALS in Europe and recently informed the company that the CHMP is trending toward a negative opinion on the AMX0035 application.

AMX0035 is being explored for the potential treatment of other neurodegenerative diseases. The formulation of RELYVRIO, ALBRIOZA and AMX0035 are identical.

RELYVRIO contains taurursodiol, which is a bile acid. In patients with disorders that interfere with bile acid circulation, there may be an increased risk for worsening diarrhea, and patients should be monitored appropriately for this adverse reaction.

Pancreatic insufficiency, intestinal malabsorption, or intestinal diseases that may alter the concentration of bile acids may also lead to decreased absorption of either of the components of RELYVRIO.

Because different enterohepatic circulation, pancreatic, and intestinal disorders have varying degrees of severity, consider consulting with a specialist.

Patients with disorders of enterohepatic circulation (e.g., biliary infection, active cholecystitis), severe pancreatic disorders (e.g., pancreatitis), and intestinal disorders that may alter concentrations of bile acids (e.g., ileal resection, regional ileitis) were excluded from the study; therefore, there is no clinical experience in these conditions.

RELYVRIO has a high salt content. Each initial daily dosage of 1 packet contains 464 mg of sodium; each maintenance dosage of 2 packets daily contains 928 mg of sodium. In patients sensitive to salt intake (e.g., those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose of RELYVRIO and monitor appropriately.

The most common adverse reactions (at least 15% and at least 5% greater than placebo) with RELYVRIO were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first 3 weeks of treatment.

ALS is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord.

Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis and eventually, death. More than 90% of people with ALS have sporadic disease, showing no clear family history.

ALS affects approximately 29,000 people in the US and more than 30,000 people are estimated to be living with ALS in Europe (European Union and United Kingdom). People living with ALS have a median survival of approximately two years from diagnosis.

Amylyx Pharmaceuticals, Inc. is committed to supporting and creating more moments for the neurodegenerative disease community through the discovery and development of innovative new treatments.

Amylyx is headquartered in Cambridge, Massachusetts and has operations in Canada and EMEA.