Clene Nanomedicine – CNM-Au8
Clene is a biopharmaceutical company developing nanotherapeutics aimed at treating failure in cellular energy production. Their lead candidate is CNM-Au8, an oral liquid aimed at enhancing energy production in neurons and oligodendrocytes (cells that produce insulation for neurons to conduct signals). It is reported by the company to also increase resistance to oxidative stress and decrease the levels of potentially toxic misfolded proteins. CNM-Au8 is currently being tested in clinical trials as a potential treatment to slow progression of ALS/MND.
On November 2, 2021, Clene announced the results from their phase 2 RESCUE-ALS clinical trial. The study was a randomized, placebo-controlled, trial of 45 participants, dosed daily with 30mg, and evaluated over 36 weeks. The primary outcome for this clinical trial was percent change in a measure called MUNIX, which estimates the number of motor neuron/muscle connections. There were several other secondary and exploratory outcomes.
There was no significant change between treated and placebo groups for MUNIX, forced vital capacity, ALSFRS-R at 36 weeks. However, this trial was small and trends in each of these measures favouring CNM-Au8 suggest that a larger trial, better powered to see subtle, but potentially meaningful effects, will be valuable. Some exploratory endpoints, including a responder analysis, defined here as someone with less than a six point decline in the ALSFRS-R over 36 weeks, demonstrated a significant difference for CNM-Au8 over placebo, as did the quality of life ALSSQOL-SF score. Futher exploratory endpoints around disease progression as measured by death or initiation of tracheostomy, NIV or gastrostomy tube, and observed versus predicted survival over 96 weeks, including an open label extension, both favoured CNM-Au8 as well. A pre-specified analysis of limb onset participants demonstrated a stronger trend towards efficacy than the full cohort.
CNM-Au8 appears, to date, to be well tolerated without any significant safety concerns.
CNM-Au8 is currently being tested in the HEALEY Platform Trial and has an expected readout of results in the second half of 2022. The announced enrollment is 161 participants, in a double blind, placebo-controlled study of daily dosing at either 30mg or 60mg, measured over 24 weeks. The treatment to placebo ratio is 3:1. The primary outcome measure is change from baseline in ALSFRS-R with secondary measures of slow vital capacity (respiratory), hand-held dynamometry (muscle strength) and survival. Further exploratory endpoints in this platform trial include DNA, neurofilament assessment, speech analysis, blood/urine/CSF biomarkers and home spirometry. It is not clear if a pre-specified subgroup analysis of limb onset participants is planned.
The SAC recommends that there is insufficient evidence at this time to conclude that CNM-Au8 provides any benefit to people with ALS. Given the trial results to date and the ongoing, larger study as an arm of the HEALEY platform trial, there is reason for cautious optimism.
International Alliance of ALS/MND Associations
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