CNM-Au8: an experimental agent for the treatment of amyotrophic lateral sclerosis (ALS)

ABSTRACT

Introduction

Two established disease-specific therapies for the treatment of amyotrophic lateral sclerosis (ALS) are riluzole and edaravone. Limitations of these medications include minimal progression slowing or survival benefit, and effectiveness only in selected populations, particularly for edaravone. AMX0035 and tofersen received US FDA approval in September 2022 and April 2023, respectively. However, phase 3 trials, further examining both medications’ efficacy, are ongoing. CNM-Au8 is an efficient catalyst of energy metabolism and is therefore a potential disease-modifying treatment for ALS, a neurodegenerative condition in which there is bioenergetics impairment.

Areas covered

In this review, we provide an overview of the current ALS treatment market, followed by a description of the pharmacodynamics and pharmacokinetics of CNM-Au8. The main preclinical and available early clinical evidence of CNM-Au8 is then described, as well as its potential as an ALS treatment.

Expert opinion

Oral treatment with CNM-Au8 failed to meet primary clinical and electrodiagnostic endpoints in phase 2/3 clinical trials. Despite this failure, a number of exploratory endpoints included in phase 2/3 trials suggest CNM-Au8 has the potential to significantly slow clinical worsening, improve quality of life, and prolong survival in ALS. Further study of CNM-Au8 in a phase 3 clinical trial is currently underway.

KEYWORDS:

• Amyotrophic lateral sclerosis
• ALS
• motor neuron disease
• CNM-Au8
• MND
• investigational drug

Article highlights

• Two established disease-specific therapies for the treatment of amyotrophic lateral sclerosis (ALS) are riluzole and edaravone. Limitations of these medications include minimal progression slowing or survival benefit and effectiveness only in select populations, particularly for edaravone. AMX0035 and tofersen received FDA approval in 2022 and 2023 respectively, both with phase 3 clinical trials ongoing. There remains an urgent need for the development of safe and effective disease-modifying ALS therapeutics.

• CNM-Au8 is an aqueous suspension of clean-surfaced, faceted gold nanocrystals shown to be an efficient catalyst for energy metabolism, and therefore a potential disease-modifying treatment for ALS, a neurodegenerative condition in which there is bioenergetics impairment.

• Oral treatment with CNM-Au8 failed to meet primary clinical and electrodiagnostic endpoints in phase 2/3 clinical trials. Despite this failure, a number of exploratory endpoints included in phase 2/3 trials suggest CNM-Au8 has the potential to significantly slow clinical worsening, improve quality of life, and prolong survival in ALS.

• Data from the phase 2/3 HEALEY ALS platform trial examining the efficacy of CNM-Au8 in the treatment of ALS are not yet published. Further study of CNM-Au8 in a phase 3 clinical trial is currently underway.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.