Clene links ALS prospect to improved survival in open-label study

Clene has linked its suspension of gold nanocrystals to decreased mortality in patients with amyotrophic lateral sclerosis, raising hopes for the candidate ahead of the readout from a larger study.

The Clene mortality data come from an open-label extension to RESCUE-ALS, a Phase II clinical trial that randomized 45 ALS patients to receive 30mg of the CNM-Au8 nanocrystals or a placebo. After 36 weeks, patients on the investigational drug performed no better statistically on a measure of the preservation of motor neuron function than their peers on placebo, causing the study to miss its primary endpoint.

However, with the study detecting a nonsignificant trend in favor of CNM-Au8, Clene concluded the miss on the primary endpoint reflected the fact the study was “underpowered​” and continued to gather data in a long-term open-label follow-up.

Now, Clene has interim data from the follow-up. Among the 22 patients initially randomized to placebo, there were 14 deaths as of July 5. One participant in the placebo group was lost to follow-up.

In the CNM-Au8 cohort, five of the 23 participants had died as of July 5. Again, one participant was lost to follow-up. Clene used the data to link early CNM-Au8 treatment to a 70% decreased risk of death.

Investors sent Clene’s share price up more than 50% in the days after the release of the results, moving it back up toward the value it commanded before the revelation that RESCUE-ALS missed its primary and secondary endpoints late last year.

Attention now turns to the upcoming results from HEALEY, a platform clinical trial that Massachusetts General Hospital is running to evaluate multiple potential ALS treatments including CNM-Au8. Topline data are due this quarter.

“Based on the larger number of patients treated in the HEALEY trial and the higher dose of CNM-Au8 being tested, we are optimistic that we will be able to adequately characterize the effects of our drug on this devastating disease​,” said Clene CEO Rob Etherington.

The CNM-Au8 part of the study has randomized 160 patients to receive the nanocrystals or a placebo. The primary endpoint is looking at the effect of CNM-Au8 on ALS progression after 24 weeks, as measured by the ALS Functional Rating Scale-Revised. Survival after 24 weeks is a secondary endpoint.

Clene and the HEALEY sponsor are studying CNM-Au8 in ALS on the strength of evidence it can provide an energetic assist to impaired motor neurons by supporting bioenergetic reactions inside the cells and eliminating harmful byproducts generated by cellular metabolism.