Amylyx Pharmaceuticals Announces Publication of Data Showing the Effect of AMX0035 on Plasma Neuroinflammatory Biomarkers in ALS
“Neuroinflammatory biomarkers are important for assessing disease progression and therapeutic response in ALS with chitinases and CRP emerging as potential treatment response biomarkers. Previous studies have shown that levels of YKL-40 in cerebrospinal fluid correlate with ALS disease progression rate, severity, and survival,” said
“Biomarkers linking clinical therapeutic effect with biological changes are of high interest in ALS, and the findings from these analyses suggest that YKL-40 could be a treatment-sensitive biomarker,” said
Of the 135 participants in the modified intent-to-treat population (ITT) of the CENTAUR trial, 126 had plasma samples available for these analyses. The analyses showed that geometric least squares (LS) mean YKL-40 and CRP plasma concentrations were 10% and 17% lower, respectively, at Week 12 and approximately 20% and 30% lower, respectively, at Week 24 in the AMX0035 versus placebo group. YKL-40 and CRP concentrations correlated with ALSFRS-R total score and ALSFRS-R slope. Geometric LS mean CHIT1 plasma levels were not significantly different between treatment groups. Further analyses of neuroinflammatory biomarkers are planned in the ongoing Phase 3 PHOENIX trial to confirm these results.
About RELYVRIO®/ ALBRIOZA™ / ALBRIOZA® / AMX0035
RELYVRIO®, an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (known as ursodoxicoltaurine outside of the
RELYVRIO® (sodium phenylbutyrate and taurursodiol) Safety Information for
WARNINGS AND PRECAUTIONS
Risk in Patients with Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders
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.
Use in Patients Sensitive to High Sodium Intake
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.
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About the CENTAUR Trial
CENTAUR was a multicenter Phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized placebo-controlled phase and an open-label long-term follow-up phase. The trial met its primary efficacy endpoint of reducing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
Overall, reported rates of adverse events and discontinuations were similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group. Detailed data from CENTAUR is published in the
The CENTAUR trial was funded, in part, by the ALS ACT grant and the ALS Ice Bucket Challenge, and was supported by
Statements contained in this press release and related comments in our earnings conference call regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, the potential of AMX0035 (sodium phenylbutyrate and taurursodiol) as a treatment for ALS and other neurodegenerative diseases including Wolfram syndrome and PSP; the Company’s beliefs regarding the benefits of AMX0035 in ALS and other neurodegenerative diseases, the potential of AMX0035 to be a foundational therapy for ALS the link between biomarker data and clinical effect in ALS; the potential for new pipeline programs and clinical indications for AMX0035; statements regarding regulatory developments; the Company’s expectations regarding its financial performance; and expectations regarding the Company’s longer-term strategy. Any forward-looking statements in this press release and related comments in the Company's earnings conference call are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Amylyx’ program development activities, Amylyx’ ability to successfully commercialize RELYVRIO in