Pictured: Clene CEO Rob Etherington/company courtesy
New results from the HEALEY ALS Platform Trial showed Clene’s investigational CNM-Au8 induced significant reductions in plasma neurofilament light chain concentrations in patients with amyotrophic lateral sclerosis, the company announced Thursday.
Treatment with CNM-Au8 likewise significantly decreased neurofilament light chain (NfL) levels in different high-risk patient subpopulations. For example, Clene’s candidate also lowered biomarker concentrations in those at risk of fast disease progression, with definite or probable amyotrophic lateral sclerosis (ALS) diagnosis, or at greater risk of death.
With these data in hand, Clene “is exploring the possibility for (sic) a [New Drug Application] filing,” Clene CEO Rob Etherington said in a statement.
“In addition to planning the global Phase III ALS trial, we are preparing the complete CNM-Au8 clinical data package, including our strong safety evidence, biomarker, survival and time-to-event analyses for FDA regulatory discussion in the third quarter,” Etherington said.
Clene is building its FDA case with biomarker data, which the regulator only recently indicated was a viable path to regulatory authorization. Biogen and Ionis’ Qalsody (tofersen) was approved in April 2023 for superoxide dismutase 1-ALS based on NfL data, setting the stage for other companies to take a similar approach to ALS drug development.
Qalsody’s approval might also signal a wider change in the industry and scientific community at large. In March 2023, an FDA advisory committee composed of nine independent experts agreed unanimously that NfL levels could be a reasonable predictor of clinical benefit.
‘Golden’ Approach to ALS
Developed using Clene’s nanotherapeutic platform, CNM-Au8 is an oral suspension of gold nanocrystals that works by catalyzing energy-producing reactions in neurons, which in turn promote remyelination and neuroprotective processes. Clene is studying CNM-Au8 as a potentially disease-modifying treatment for ALS as well as other neurodegenerative diseases, including multiple sclerosis and Parkinson’s disease.
Thursday’s data drop continued CNM-Au8’s comeback after it first missed HEALEY’s primary endpoint in October 2022. The nanotherapy did not significantly slow the decline in the patients’ ALS Functional Rating Scale Revised scores, nor did it yield significant benefits in terms of secondary endpoints, including slow vital capacity and Combined Assessment of Function and Survival.
Still, CNM-Au8 led to survival benefits, significantly reducing the risk of death or death combined with permanently assisted ventilation.
These promising data pushed Clene to look deeper into CNM-Au8’s efficacy and in March 2023, the company posted follow-up results demonstrating that CNM-Au8 significantly delayed disease progression in ALS patients. The oral suspension likewise cut the risk of death or permanent ventilation by 98%, feeding tube placement by 74% and ALS-related hospitalization by 84%.
“When supported by a confirmatory trial, this would give people living with ALS longer periods of independence, which are precious to them and their families,” Etherington said in a prepared statement at the time.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
