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Clene Nanomedicine’s ALS Therapy Fails in Phase 2 Trial

November 2, 2021

Clene Nanomedicine reported that its potential first-in-class, regenerative therapy CNM-Au8 did not meet the primary or secondary endpoints in a phase 2 trial evaluating it as a disease modifying treatment for people with early neurodegenerative disease amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rare and fatal condition that affects motor neurons (a type of nerve cell that controls voluntary movements) in the brain and spinal cord. When the nerve cells die, the brain can no longer initiate and control muscle movement, which results in severe disability, paralysis and eventually death.

People with ALS may lose the ability to speak, eat, move and breathe. The rate of progression between individuals is variable and the natural history generally reflects progressive worsening over time until death occurs. The average life expectancy from symptom onset is between two and five years. Currently approved medications may slow disease progression, but ALS management is mostly supportive, palliative and symptom based.

The catalytically active nanocrystals of Clene’s CNM-Au8 drive critical cellular energy producing reactions in the brain that enable neuroprotection and remyelination by increasing neuronal and glial resilience to disease-relevant stressors. CNM-Au8 crosses the blood-brain barrier and is not associated with the toxicities related to synthetic gold compounds or nanoparticles manufactured via alternative methods.

RESCUE-ALS was a 36-week randomized, placebo-controlled phase 2 clinical trial that enrolled 45 patients with early ALS, randomized 1:1 to treatment with CNM-Au8 at 30 mg daily or matching placebo on top of standard of care. The primary endpoint of the trial was the percent change of the sum of Motor Unit Number Index (MUNIX) from baseline to week 36. Secondary endpoints were the change in forced vital capacity (FVC) and the absolute change in MUNIX values to week 36. Exploratory endpoints included multiple clinically relevant measures of ALS: disease progression, ALSFRS-R decline, and ALSSQOL-SF.

The trial did not meet the primary or secondary endpoints, MUNIX and FVC, at week 36. However, an efficacy signal was observed for the MUNIX endpoint at week 12. Furthermore, in a pre-specified analysis in the subset of limb onset ALS, CNM-Au8 demonstrated a significant treatment effect in MUNIX at week 12 and a trend for improvement at week 36. Limb onset ALS accounts for approximately 70 percent of the ALS population. MUNIX is a neurophysiological biomarker that estimates the number of functioning lower motor neurons serving selected muscles.

Clinically relevant exploratory endpoints through trial week 36 demonstrated significant benefits with CNM-Au8 treatment, including slowing ALS disease progression, decreasing the proportion of participants with an ALS Functional Rating Scale Revised (ALSFRS-R) 6-point decline, and improving quality of life as measured by the ALS Specific Quality of Life (ALSSQOL-SF). In addition, RESCUE-ALS showed evidence for a potential long-term survival benefit when comparing the survival of the trial population to the validated ENCALS predictive model.

“These data are very encouraging to us in the ALS research and treatment community as they demonstrate clinical benefits with CNM-Au8 treatment in outcomes that matter to patients and provide evidence for improved long-term survival,” said Professor Matthew Kiernan, Bushell Chair of Neurology, University of Sydney and one of the trial’s clinical advisors. “RESCUE-ALS was a proof-of-concept trial intended to establish that treatment of neuronal energetic failure can provide disease-modifying effects in ALS. I am pleased to see the potential effectiveness of CNM-Au8 demonstrated in this trial, and it is important to confirm these results in a larger clinical trial.”

CNM-Au8 was found to be well-tolerated through 36 weeks of oral daily dosing. There were no reported serious adverse events related to CNM-Au8 treatment. Treatment-emergent adverse events were predominantly mild-to-moderate in severity. The most frequently reported adverse events associated with CNM-Au8 treatment included aspiration pneumonia (n=3) and transient gastrointestinal distress (n=2). Topline results from RESCUE-ALS are expected to be presented at the upcoming International Symposium on ALS/MND, which will take place December 8-10, 2021.

Despite not meeting trial endpoints, Clene is continuing the development of CNM-Au8 in a registrational phase 3 trial. “We believe these results show the potential of CNM-Au8 to bring meaningful benefit to people living with ALS,” said Rob Etherington, CEO of Clene. “Befitting of Lou Gehrig, whose legacy is intertwined with the disease, we swung for the fences and ended with a stand-up triple. In the second half of next year, we expect to report results from the HEALEY ALS Platform Trial with the objective of confirming CNM-Au8 as an effective disease-modifying therapy for people with ALS.”   

The phase 2 trial in Australia was supported by a grant from the nonprofit FightMND. “These clinical trial results are encouraging for people with ALS. By achieving clinically relevant endpoints, this trial demonstrates the potential for CNM-Au8 to support neuronal health,” said Bec Sheean, research director of FightMND.

Author: Rare Daily Staff

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