New HEALEY-ALS Trial Results Show CNM-Au8’s Effect on Survival, Neurofilament Light

Author(s):

CNM-Au8, an oral suspension of clean-surfaced, catalytically-active gold nanocrystals, resulted in prolonged survival and reductions in neurofilament light, a prominent biomarker of neuroaxonal damage.

Benjamin Greenberg, MD

New data from an open-label extension of the pivotal HEALEY-ALS platform trial showed that treatment with investigational CNM-Au8 (Clene Nanomedicine) resulted in extended survival as compared with matched controls, as well as reductions in neurofilament light (NfL), a biomarker of neuroaxonal damage, in patients with amyotrophic lateral sclerosis (ALS). Throughout the treatment period, the agent was safe and well-tolerated, consistent with previous studies.¹

The findings, presented at the European Network for the Cure of ALS (ENCALS) meeting in Stockholm, Sweden, included participants treated with CNM-Au8 30 mg (n = 59), including ex-placebo participants (n = 11) who transitioned to CNM-Au8 in the OLE, with complete baseline covariates. All told, results showed a 60% decreased risk of death while on CNM-Au8 when compared with matched controls from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) for up to 3.5 years of follow-up (covariate-adjusted hazard ratio, 0.431; 95% CI, 0.276-0.672; P = .0002).

CNM-Au8, Clene’s lead drug candidate, is an oral suspension of clean-surfaced, catalytically-active gold nanocrystals. In addition to ALS, it remains in development for several other neurologic conditions, including multiple sclerosis and Parkinson disease. The analysis of CNM-Au8 highlighted up to 42 months (3.5 years) of survival follow-up and 76 weeks of long-term NfL biomarker results, including a responder subset from the HEALEY-ALS Platform trial.

The NfL analysis included 55 participants with ALS who showed consistent NfL declines of at least 10 pg/mL across all post-baseline measures following the start of CNM-Au8 treatment. According to Clene, the responders demonstrated an average NfL reduction of 28% at week 76, which was suggestive of decreased axonal loss on an ongoing basis (change, 0.72; 95% CI, 0.67-0.79; P <.0001).

"The clinical evidence of plasma neurofilament reduction, as well as the long-term improved survival results up to 3.5 years compared to an established multi-study ALS dataset of more than 12,000 patients across multiple clinical centers provides further evidence to strongly support CNM-Au8 as a potential treatment for ALS," Benjamin Greenberg, MD, vice chair of clinical & translational research at UT Southwestern Medical Center, and head of Medical at Clene, said in a statement.¹

The NfL results were based on earlier announced analyses of plasma NfL collected from participants (n = 99) in the HEALEY OLE who were treated with CNM-Au8 30 mg through week 76 compared to participants treated with placebo for 24 weeks prior to crossing over to active treatment for up to 52 weeks. At week 76, the geometric mean ratio of plasma NfL levels relative to placebo was 0.841 (95% CI, 0.73-0.98; P = .023).

Reductions in NfL are considered significant following the 2022 approval of tofersen (Qalsody; Biogen), an antisense oligonucleotide that gained FDA greenlight based on change in NfL as a surrogate biomarker. In the phase 3 VALOR study (NCT02623699), one of the major trials in its approval process, early- and delayed-start tofersen groups saw reductions of 51% and 41%, respectively, in NfL after 12 months of treatment. Following an AdComm hearing, it was deemed that reductions in surrogate NfL may be reasonably likely to predict clinical benefit.²

In the phase 2 VISIONARY-MS trial (NCT03536559), data announced earlier this year showed that CNM-Au8 resulted in improved progressive vision and cognition in patients with relapsing MS. After 144 total weeks of treatment, investigators observed a least-square mean improvement of 8.70 (SE, 1.88; 95% CI, 5.0-12.4; P <.0001) letters on low contrast visual acuity (LCLA) change across both eyes. Cognition, assessed through the symbol digit modality test (SDMT), showed least-square mean changes of +8.03 (SE, 1.52; 95% CI, 5.01-11.0; P <.0001) vs the original randomization baseline.³

REFERENCES
1. Clene Presents Extended Survival Data Through 3.5 Years and New NfL Responder Results with CNM-Au8® 30 mg Treatment from the HEALEY ALS Platform Trial Open Label Extension at the 2024 ENCALS Meeting. News release. June 18, 2024. Accessed June 18, 2024. https://finance.yahoo.com/news/clene-presents-extended-survival-data-110000050.html
2. Miller TM, Cudkowicz ME, Genge A, et al. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med. 2022;387:1099-1110. doi:10.1056/NEJMoa2204705.
3. Clene Reports Significant Improvement in Vision and Cognition With CNM-Au8® Treatment in VISIONARY-MS Trial Long-Term Open Label Extension. News release. Clene Nanomedicine. January 8, 2024. Accessed June 18, 2024. https://finance.yahoo.com/news/clene-reports-significant-improvement-vision-120000893.html