CNM-Au8 for ALS
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What is CNM-Au8 for ALS?
CNM-Au8 is an experimental oral therapy being tested as a potential treatment for people with amyotrophic lateral sclerosis (ALS).
The therapy has been granted orphan drug status by the U.S. Food and Drug Administration for the treatment of ALS. The designation provides a series of incentives intended to speed CNM-Au8’s clinical development and regulatory review. In the European Union, a committee issued a positive opinion for granting it a similar designation for ALS.
Clene Nanomedicine, the company developing CNM-Au8, also is testing it for the treatment of Parkinson’s disease and multiple sclerosis (MS), two other neurodegenerative conditions.
Therapy snapshot
| Treatment name: | CNM-Au8 |
| Administration: | Being tested in ALS as an oral liquid formulation |
| Clinical testing: | Completed a Phase 2 trial and the HEALEY ALS Platform trial in ALS |
How does CNM-Au8 work in ALS?
ALS is a neurodegenerative condition in which motor neurons, the nerve cells that control voluntary muscle movement, become progressively damaged and die. This leads to generalized muscle weakness, which causes difficulties with moving, breathing, eating, and speaking.
CNM-Au8 in an oral liquid suspension of gold nanocrystals designed to support the energetic needs of nerve cells and other cells of the nervous system, improving their general health and survival. It also helps to remove toxic molecules from cellular metabolism that can cause oxidative stress, a type of cellular damage that has been implicated in ALS progression.
In preclinical studies, CNM-Au8 improved motor neuron survival and function in lab-grown cells and significantly extended survival in a mouse model of ALS without causing side effects.
The therapy can cross the blood-brain barrier, a highly selective membrane that protects the brain and spinal cord from pathogens and large molecules circulating in the bloodstream. This barrier is a common obstacle for therapies targeting the brain, limiting their effectiveness.
How will CNM-Au8 be administered in ALS?
CNM-Au8 is a drinkable formulation of gold nanocrystals that comes in a dark red or purple-colored liquid suspension.
In ALS clinical trials, the treatment is being tested at daily doses of either 30 or 60 mg. However, because the greatest benefits were seen with the 30 mg dosage, the company selected this dose for continued development in ALS.
CNM-Au8 in ALS clinical trials
CNM-Au8 was first tested in a group of 86 healthy volunteers who entered a first-in-human Phase 1 clinical trial (NCT02755870). Participants were assigned randomly to receive the medication — at doses ranging from 15 to 90 mg — or a placebo, either in a single administration, or daily for 21 days.
Results showed CNM-Au8 was safe and well tolerated. The most common treatment-related side effects included headache, drowsiness, fatigue, abdominal pain, and diarrhea. No drug-related adverse events leading to treatment discontinuation and no serious side effects were reported in the trial.
RESCUE-ALS trial
After the promising Phase 1 trial findings, a Phase 2 clinical trial, called RESCUE-ALS (NCT04098406), was launched as a proof-of-concept study to assess the safety and efficacy of CNM-Au8 in people with ALS.
The trial enrolled 45 patients with early ALS — whose first symptoms had developed in the past two years — and randomly assigned them to receive either daily treatment with 30 mg CNM-Au8 or a placebo for 36 weeks (about eight months). All could continue to receive standard treatment with riluzole-based therapies.
The main goal was to assess if CNM-Au8 could prevent the loss of motor neurons, as measured by Motor Unit Number Index (MUNIX) scores. RESCUE-ALS was the first known study that used MUNIX as a primary measure of efficacy.
Top-line results showed the treatment failed to significantly alter MUNIX scores compared with a placebo, and also did not significantly slow lung function decline, a key secondary goal.
However, Clene later noted that MUNIX scores are mostly measured in nerves controlled by the spinal cord, which are typically not affected in people with bulbar-onset ALS — a disease form marked by initial symptoms of muscle weakness in the head and neck, which accounts for about 30% of the ALS population.
A prespecified analysis including only patients with limb-onset disease, whose symptoms start in the limbs, showed that those treated with a placebo experienced a 40% decline in MUNIX scores versus 20% for those on CNM-Au8 — overall indicating that treatment slowed the loss of motor neurons by about 45%.
Additional analyses of the whole group also demonstrated the therapy significantly slowed disease progression, as measured with the ALS Functional Rating Scale Revised (ALSFRS-R) scores, and improved quality of life.
Also, CNM-Au8 significantly reduced the risk of ALS disease progression — defined as the occurrence of death, ventilatory support, or feeding tube placement — by about 37%, with benefits being similar in limb- and bulbar-onset patients.
RESCUE-ALS open-label extension
After completing the main trial, the majority of patients chose to join an open-label extension (OLE) study (NCT05299658) in which all are receiving the investigational therapy for up to 120 weeks (more than two years).
Data spanning RESCUE-ALS and its extension portion showed that patients initially assigned to CNM-Au8 had a significantly lower rate of disease progression after 48 weeks than those who switched to CNM-Au8 from a placebo — a 2.6 point difference in ALSFRS-R scores.
While those findings were expected, as placebo group patients would not yet have achieved effective bloodstream concentrations of the therapy, patients on continuous CNM-Au8 still experienced a slower disease progression across weeks 60 to 120, when all OLE patients had effective concentrations of CNM-Au8.
Compared with a 9-month delayed treatment start, early treatment with CNM-Au8 also was associated with a significant 60% lower risk of death.
The findings were consistent with an earlier analysis showing a 57% reduction in mortality risk compared with what would be expected for CNM-Au8-treated patients if they had not received treatment.
HEALEY ALS Platform trial
The HEALEY ALS Platform trial (NCT04297683) is the first clinical study designed to simultaneously test several ALS treatment candidates against a shared placebo group, which is expected to cut costs and accelerate the development of new therapies.
The trial’s CNM-Au8 Phase 2/3 arm (NCT04414345) enrolled 161 ALS patients whose first signs of muscle weakness developed less than three years before entering the trial. They were assigned randomly to receive either 30 or 60 mg of CNM-Au8, or a placebo, daily for 24 weeks.
The primary goal was to evaluate whether CNM-Au8 could slow functional decline as measured by ALSFRS-R scores. Secondary measures included a combined assessment of function and survival, changes in lung function, and survival.
Top-line data showed the trial failed to meet its main goal of slowing functional decline, and also did not demonstrate a significant improvement in measures of lung function nor in the joint assessment of function and survival.
However, exploratory analyses showed the 30 mg dose reduced — by more than 90% — the risk of death and the combined risk of death and need for permanently assisted ventilation after six months. Significant reductions also were observed in the risk of several other disease milestones, such as needing a feeding tube (by 74%), requiring assisted ventilation (by 63%), or being hospitalized due to ALS (by 84%).
Overall, the risk of ALS clinical worsening — defined as a first occurrence of either death, needing a breathing or feeding tube, or the initiation of permanent assisted ventilation — was reduced by 74%.
The treatment was generally well tolerated, with no serious treatment-related side effects or significant safety issues reported.
After completing the placebo-controlled part, participants could join an open-label extension phase, in which all are receiving the 30 mg dose of CNM-Au8.
According to Clene, an international Phase 3 trial, called RESTORE-ALS, is being planned to continue assessing the safety and efficacy of 30 mg CNM-Au8.
Expanded access programs
Two expanded access programs, or EAPs, are currently ongoing to provide access to CNM-Au8 to patients outside clinical trials — CNMAu8.EAP01 (NCT04081714) and CNMAu8.EAP02 (NCT05281484). Patients are being recruited at several of HEALEY’s participating sites, with the collaboration of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital.
Researchers will evaluate the treatment’s safety and efficacy, which may provide additional long-term data for review by regulatory entities.
Common side effects of CNM-Au8
To date, no treatment-related serious side effects of CNM-Au8 have been reported in ALS clinical trials. The most common side effects deemed related to treatment include:
- aspiration pneumonia
- nausea
- bruising (contusion)
- abdominal discomfort.
ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about CNM-Au8
CNM-Au8 is an experimental therapy that is still in clinical testing as a potential treatment for amyotrophic lateral sclerosis (ALS). It is made of gold nanocrystals designed to support the energetic needs of nerve cells and help to remove toxic molecules from cellular metabolism, reducing nerve cell damage. In clinical trials, the treatment significantly slowed disease progression and the risk of reaching multiple disease milestones, and improved survival in ALS patients.
As Phase 2 clinical trials testing CNM-Au8 have shown promising results in people with amyotrophic lateral sclerosis (ALS), Clene Nanomedicine, the company developing CNM-Au8, now is planning to launch a Phase 3 trial to confirm the benefits of the liquid suspension in a larger population of patients. Data from this trial, called RESTORE-ALS, may support an application to the U.S. Food and Drug Administration, but it is still too early to know if or when the medication might be approved.
The most common side effects deemed related to CNM-Au8 in clinical trials involving people with amyotrophic lateral sclerosis included aspiration pneumonia, nausea, bruising, and abdominal discomfort. No serious side effects deemed related to treatment have been reported. Patients should speak with their healthcare team to know more about which side effects could be expected when beginning treatment with CNM-Au8.
Because CNM-Au8 is still in the early stages of development, studies examining its interaction with alcohol are still lacking. It is recommended that patients discuss this issue with their doctors to know if it is safe to drink alcohol while on this therapy.
In the CNM-Au8 arm of the HEALEY ALS trial, significant improvements in multiple measures of disease progression and survival were seen as early as six months after beginning treatment. However, the exact timing for experiencing an effect from CNM-Au8 is unknown, as it can vary from patient-to-patient. A conversation with a healthcare provider may help patients better understand when CNM-Au8 may have an effect in their specific case.
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