Amylyx Pharmaceuticals Announces Oral Presentation of Safety and Tolerability Data on AMX0035 from Clinical Trials at 2022 American Academy of Neurology Annual Meeting
Amylyx Pharmaceuticals announced data from the CENTAUR and PEGASUS clinical trials, confirming that AMX0035 is safe and well tolerated in patients with amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). The majority of treatment-emergent adverse events (TEAEs) were gastrointestinal, with no new safety signals identified. These findings clarify the safety profile of AMX0035. Participants from both trials reported similar incidences of TEAEs, attributed largely to disease progression in ALS. The data will be presented at the AAN conference on April 4, 2022.
- AMX0035 demonstrated a safety profile consistent with previously published data.
- No new safety signals were identified, indicating a favorable risk profile.
- The majority of adverse events were non-serious and gastrointestinal in nature.
- The incidence of treatment-emergent adverse events was higher in ALS patients, attributed to disease progression.
- Summary of data from CENTAUR and PEGASUS showed AMX0035 was safe and well tolerated in clinical trials in amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD)
- Majority of treatment-emergent adverse events (TEAEs) associated with AMX0035 were gastrointestinal in both trials with no new safety signals identified
- Findings help further clarify the safety profile of AMX0035
“The results of this analysis provide additional insights and clarifications on the overall safety and tolerability of AMX0035 in people with two different conditions, ALS and AD, and how these diseases might impact the results,” said
In the CENTAUR trial participants (AMX0035, n=89; placebo, n=48) completing the 24-week randomized phase were eligible to enroll in an open-label extension phase and receive AMX0035 (≤132 weeks, week 24 reported). PEGASUS was a 24-week randomized trial in adults with AD or mild cognitive impairment (AMX0035, n=51; placebo, n=44). Evaluation of AMX0035’s safety and tolerability was the primary objective of both trials. Results of the summary of the clinical trials showed that:
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The majority of TEAEs associated with AMX0035 were gastrointestinal, consistent with the observed individual safety profiles of the components of AMX0035.
- In both trials, diarrhea and, to a lesser extent, abdominal discomfort/pain, abdominal distension, and dyspepsia were more frequent with AMX0035 versus placebo.
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No new safety signals were identified.
- While the majority of participants in the phase 2 studies experienced TEAEs, they were largely non-serious, mild or moderate in intensity, and assessed as unrelated to treatment with study medication.
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Findings in AD further elucidated the safety profile of AMX0035, as TEAEs in the CENTAUR trial appear to have been largely disease driven.
- Further comparison of the TEAEs across both trials suggests that the higher overall incidence of TEAEs in the CENTAUR trial was attributable to symptoms of natural ALS progression, namely muscular weakness and falls, which were among the most common TEAEs in CENTAUR.
“We are committed to the discovery and development of new treatment options with the potential to offer hope and extend function in those living with neurodegenerative diseases affected by the progressive loss of certain abilities,” said
The abstract, “Safety of a Fixed-Dose Coformulation of Sodium Phenylbutyrate and Taurursodiol in Amyotrophic Lateral Sclerosis and Alzheimer’s Disease: Integrated Clinical Trials Experience,” was selected for an oral presentation in the ALS and Motor Neuron Disorders scientific session, and will be presented on
About AMX0035
AMX0035 is a proprietary oral fixed-dose combination of two small molecules: sodium phenylbutyrate (PB), which is a small molecular chaperone designed to reduce the unfolded protein response (UPR), preventing cell death resulting from the UPR, and taurursodiol (TURSO; also known as ursodoxicoltaurine), which is a Bax inhibitor designed to reduce cell death through apoptosis. PB and TURSO were combined in a fixed-dose formulation in an effort to reduce neuronal death and dysfunction. AMX0035 is designed to target the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.
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 (≥
The CENTAUR trial was funded, in part, by the ALS ACT grant and the ALS Ice Bucket Challenge, and was supported by
About the PEGASUS Trial
PEGASUS (NCT03533257) was a randomized, double-blind, multi-center, placebo-controlled trial evaluating the safety, tolerability and activity of AMX0035 in 95 adults with dementia or late mild cognitive impairment (MCI) due to AD over 24 weeks of treatment. The trial was designed to evaluate tolerability in this patient population while also assessing efficacy measures and diverse, disease-relevant markers to allow for evaluation and correlation of imaging-based markers, neurobiological changes, functional measures, and cognitive outcomes in a broad group of people with AD.
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Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning the of 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, statements regarding: Amylyx’ strategy, business plans and objectives for 2022 and beyond; the potential of AMX0035 as a treatment for ALS and AD and the efficacy and safety profile of AMX0035; the timing, progress and results of our Phase 3 PHOENIX clinical trial of AMX0035; the potential of AMX0035 or other future therapeutic candidates as a treatment for neurodegenerative diseases; and expectations regarding our longer-term strategy. Any forward-looking statements in this statement 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 execute on its commercial and regulatory strategy, regulatory developments, expectations regarding the timing of FDA review of AMX0035 for the treatment of ALS, Amylyx’ ability to fund operations, and the impact that the ongoing COVID-19 pandemic will have on Amylyx’ operations, as well as those risks and uncertainties set forth in Amylyx’
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