CNM-Au8, an investigational disease-modifying therapy for people with early amyotrophic lateral sclerosis (ALS), failed to prevent motor neurons loss and lung function decline relative to a placebo, according to top-line data from the RESCUE-ALS Phase 2 clinical trial.
The trial, in other words, did not meet its primary and a key secondary goal after 36 weeks of treatment: higher Motor Unit Number Index (MUNIX) scores — which measure the number, function, and health of motor neurons — and greater forced vital capacity (FVC), a measure of lung health. However, a trend toward better MUNIX scores was evident at 12 weeks among patients taking CNM-Au8.
CNM-Au8, a gold nanocrystal liquid suspension, also demonstrated a significant effect in MUNIX at 12 weeks among patients with limb onset ALS, and a trend toward improvement at 36 weeks. Limb onset occurs in about 70% of all ALS patients.
Exploratory measures also showed that CNM-Au8 significantly slowed disease progression, as assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R), with a smaller proportion of treated patients with a six-point decline in that scale. In addition, quality of life at week 36 was significantly better in patients taking the investigational therapy, and there was evidence of benefit in long-term survival.
“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,” Matthew Kiernan, PhD, a professor at the University of Sydney and one of the trial’s clinical advisers, said in a press release.
“RESCUE-ALS was a proof-of-concept trial intended to establish that treatment of neuronal energetic failure can provide disease-modifying effects in ALS,” Kiernan added. “I am pleased to see the potential effectiveness of CNM-Au8 demonstrated … and it is important to confirm these results in a larger clinical trial.”
CNM-Au8 contains a suspension of nanocrystalline gold designed to promote nerve cell function and survival by increasing energy production within cells, while protecting them from oxidative stress. As a treatment, it aims to prevent nerve cell death and slow ALS progression.
The Phase 2 RESCUE-ALS trial (NCT04098406), conducted in Australia, tested oral CNM-Au8 at 30 mg daily against a matching placebo, both given each morning for 36 weeks (about eight months) along with standard care to 45 people with early ALS.
Its main goal was changes in the number, function, and health of motor neurons, or nerve cells, controlling hand, arm, leg, and feet muscles, using the MUNIX(4) sum, an established predictor of clinical decline.
Interim results had suggested that CNM-Au8 could slow ALS progression relative to its natural course, but the recently reported top-line data showed that it failed to outperform placebo in the MUNIX(4) scores and failed in a key secondary endpoint, that of lung health decline.
Additional secondary and exploratory measures, however, found meaningful benefits in certain groups of ALS patients, as well as slower disease progression, better quality of life, and a potential for longer survival.
Over the eight-month trial, the therapy was also found to be well-tolerated with no reported serious adverse events related to treatment. Related adverse events, or side effects, were mainly mild to moderate, with aspiration pneumonia and transient digestive tract distress being the most frequent.
CNM-Au8 is also being evaluated alongside four other potential ALS therapies in the HEALEY ALS Platform Trial (NCT04297683), a multicenter and multiple therapy trial aiming to speed the development of promising treatments.
CNM-Au8’s HEALEY arm (NCT04414345), enrolling by invitation, reached 50% of its intended patient group in March and will include up to 160 adults with familial or sporadic ALS. Clene Nanomedicine, the company developing CNM-Au8, expects data from HEALEY toward late 2022.
A U.S.-based Phase 2 trial, called REPAIR-ALS (NCT03843710), is set to assess CNM-Au8’s safety and metabolic effects on the central nervous system (brain and spinal cord) in up to 24 recently diagnosed adults. The open-label study may not yet be enrolling.
“We believe these [RESCUE-ALS] results show the potential of CNM-Au8 to bring meaningful benefit to people living with ALS,” said Rob Etherington, Clene’s CEO. “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.”
Bec Sheean, PhD, research director of FightMND — a nonprofit organization in Australia that helped to fund RESCUE-ALS — also thought its results “encouraging.”
“By achieving clinically relevant endpoints, this trial demonstrates the potential for CNM-Au8 to support neuronal health,” Sheean said. “We are excited to see CNM-Au8 continue its advancement into the clinic so that we can bring this potentially transformative treatment to patients.”
Clene plans to detail top-line RESCUE-ALS findings at the International Symposium on ALS/MND, set for Dec. 8–10.
“The results of RESCUE-ALS add to our expanding body of evidence that cellular energetic failure is an important pathophysiological mechanism in ALS,” said Robert Glanzman, Clene’s chief medical officer. “We thank the trial participants and their families for their willingness to engage in clinical research, the site investigators for their research excellence and dedication to patients, and FightMND of Australia for substantially funding the trial.”