Clene Could be Big Part of "Momentous Year" for ALS Research

Clene CEO Rob Etherington_Clene Inc

Clene President and CEO Rob Etherington/Courtesy Clene Inc. 

Amyotrophic lateral sclerosis (ALS) is a devastating disease. For years, pharmaceutical companies have been striving to develop therapies to help patients who face certain death but have mostly come up short. Now though, there is a renaissance in ALS drug development with multiple shots being taken on goal, including Clene, Inc.’s add-on treatment, CNM-Au8, which is generating positive clinical data.

CNM-Au8 is an investigational gold bioenergetic nanocatalyst that can be used as an add-on to care in multiple neurodegenerative diseases, including ALS, Parkinson’s and multiple sclerosis. The investigational asset is designed to catalyze biocelluar reactions and, so far in clinical studies, is “golden.”

This month, Clene presented updated clinical data from its Phase II RESCUE-ALS study that indicate the addition of its nanocrystal asset boosts chances of survival. Interim data show an approximately 70% decreased risk of death for participants who entered the RESCUE-ALS long-term open-label extension.

The strength of the updated data from the RESCUE-ALS study could be a good predictor of what Clene hopes to see later this summer from the Phase III HEALEY study, which is assessing multiple treatments at one time including CNM-Au8. Data from the HEALEY study is expected in the third quarter. Once the data is unblinded, it will be sorted by teams from Harvard University and Massachusetts General Hospital.

“The critical thing is going to be the HEALEY ALS Platform study. By the end of the summer, we’ll understand whether or not Au8 can improve ALS,” Clene President and CEO Rob Etherington told BioSpace.

ALS is a progressive neurodegenerative disease that affects neurons in the brain and the spinal cord. Patients with ALS eventually lose the ability to control muscle movement, which eventually leads to total paralysis and then death within two to five years of diagnosis. The U.S. Centers for Disease Control and Prevention estimates that approximately 12,000 to 15,000 Americans have ALS, with about 5,000 to 6,000 new cases diagnosed annually. 

If the data pans out, Etherington explained that it will likely lead Clene to seek regulatory approval for CNM-Au8 as an add-on treatment for ALS. Improvement in survival is a key endpoint in the study. Etherington said the company will wait to see full mortality data from the study, which should be available by the end of 2022. That would put a New Drug Application filed with the U.S. Food and Drug Administration in the first part of 2023. If the FDA awards CNM-Au8 Fast Track designation, that could mean potential approval by the end of 2023 or early 2024, Etherington said.

Data from RESCUE-ALS showed that treatment with CNM-Au8 significantly slowed progression of ALS and improved quality of life as it is measured by the ALS Specific Quality of Life questionnaire. It also prevented clinical worsening of the disease, which included the need for a tracheotomy, or full-time use of a CPAP machine to assist breathing or gastrostomy tube to eat. Also, CNM-Au8 treatment resulted in improved brain NAD+/NADH ratio in patients. The data suggest CNM-Au8’s ability to engage its target and support its potential as a disease-modifying therapy, Clene Chief Medical Officer Robert

Glanzman, M.D., said in a statement at the time the data was announced.

In the fall of 2021, Clene’s initial data from RESCUE-ALS was slightly tarnished after the company announced that CNM-Au8 failed to meet its primary Motor Unit Number Index biomarker endpoint, or its secondary forced vital capacity endpoint. As Clene examined the data, Etherington said the company learned that the benefits of the CNM-Au8 were primarily seen in those patients with limb onset ALS as opposed to bulbar ALS. When assessing the patients who participated in the study, Etherington said the Clene team discovered there were more bulbar patients than those with limb onset. Bulbar patients did not see much improvement from CNM-Au8, while limb onset patients saw 45% improvement, Etheridge said.

Additionally, Etherington said Clene also has emerging evidence of motor neuron protection with CNM-Au8. “Nobody has ever seen that before,” he said.

Currently, there are only two drugs approved in the U.S. to treat ALS, Riluzole, which has different available formulations, and Mitsubishi Tanabe’s Radicava, which when it was approved in 2017, was the first new ALS treatment in 22 years. A third drug could soon join the ranks of approved treatments for ALS. Today, an FDA advisory committee will review clinical data for Amylyx Pharmaceuticals’ AMX0035, a fixed-dose combination of two small molecules, sodium phenylbutyrate and taurursodiol, which were combined in an effort to reduce neuronal death and dysfunction.

AMX0035 is designed to target the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases. If the advisory committee gives the green light to AMX0035, the FDA could approve the medication by the end of June.

With Wednesday's advisory meeting, Etherington expressed excitement for the ALS community. He noted that there has been little progress in developing therapies for the disease. If AMX0035 is approved and the data from the HEALEY trial supports CNM-Au8’s efficacy, Etherington said 2022 could be a momentous year for ALS research.

“These are exciting times for ALS,” he said.

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