Axoltis Pharma is undertaking additional analysis of its Phase II amyotrophic lateral sclerosis (ALS) trial after it failed to meet its primary endpoint.
In patients treated with NX210c during the SEALS study (NCT06365216), there was no benefit in neurofilament light chain (NfL) levels or albumin quotient between cerebrospinal fluid and blood (Qalb) after six weeks, missing the primary endpoint.
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There was a numerical benefit in the decrease of NfL in the blood, with 25.4% of patients in the NX210c arms of the study compared to 11.8% among the placebo cohort, but this data was not significant. NfL is a biomarker used to measure neuronal and axonal damage.
There were, however, “consistent positive trends” observed in secondary and exploratory assessed parameters, Axoltis added.
In post-hoc analyses, the decline rate of clinical function, assessed by the Harmonised Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) slope, was substantially reduced versus placebo, with a 0.67 point/month reduction for 5mg/kg arm, 0.9 for 10mg/kg cohort and 1.14 for placebo after six weeks. This corresponds to an average reduction of 41% for 5mg/kg and 21% for 10mg/kg. This effect improved through week 10 and four months.
Benefits were seen on the motor function subscale, with an average reduction of about 64% for 5mg/kg and 33% for 10mg/kg at weeks six and 10.
Axoltis has also touted that data showed a significant decrease in blood claudin-5, which is a protein released into the bloodstream when the blood-brain barrier (BBB) is disrupted, in the 10mg cohort, suggesting barrier recovery.
Based on the exploratory and secondary endpoint data, Axoltis is looking to the next clinical steps for NX210c in ALS.
There are already additional analyses underway, including a 10-month follow-up of the Phase II trial patients and the PK/PD relationship in a bid to determine the potential optimal regimen of treatment.
Data is set to be presented in more detail during Neuroscience 2026, the annual meeting of the Society for Neuroscience, in Washington on 14 to 18 November.
This comes as the ALS space once again shows its challenging nature for drug developers.
Novartis quietly reported a negative Phase II trial of its ALS drug VHB937B1 in August 2026, stating that the ASTRALS trial failed to meet its primary or secondary endpoints. As a result, the drug has been discontinued in ALS.
Amylyx Pharmaceuticals’ Relyvrio (sodium phenylbutyrate and taurursodiol) was granted accelerated approval in 2022 but, following a confirmatory study failure, the disease-modifying therapy was pulled from the market in 2024.
Also in 2024, Sanofi and Denali Therapeutics’ SAR443820 failed to meet its primary endpoint in a Phase II trial, and Ferrer Internacional’s FAB122 failed to meet its primary endpoint in a Phase III study.
While Biogen gained approval from the US Food and Drug Administration (FDA) for Qalsody (tofersen) for a subset of patients with SOD1-related genetic ALS in 2023, excluding Amylyx’s now-pulled therapy, this was the first approval seen on the market since 2017, when Mitsubishi Tanabe Pharma’s Radicava (edaravone) was approved. Before that, the only approved drug for ALS was riluzole.
