In December 2023, clinical-stage biopharmaceutical company Clene Nanomedicine (“Clene”) shared that it had met with the U.S. Food and Drug Administration (FDA) regarding Accelerated Approval for CNM-Au8^®, an experimental therapy for amyotrophic lateral sclerosis (ALS). Accelerated approval allows for the earlier approval of therapies for serious conditions that fill an unmet medical need, and is based on a surrogate trial endpoint.

CNM-Au8 is described as:

a gold nanocrystal suspension currently in development as a disease-modifying treatment for people living with Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson’s Disease (PD).

Clene believes that CNM-Au8 is neuroprotective. Additionally, the company claims that CNM-Au8 can increase overall lifespan while reducing neurofilament light chain; this has been an important and burgeoning focus in research on ALS.

However, Jacob Bell reports in BioPharma Dive that the FDA declined to grant Accelerated Approval to CNM-Au8. The FDA shared that the agency does not feel that there is enough evidence to support Accelerated Approval. Findings from an open-label extension study suggest that CNM-Au8 reduced plasma neurofilament light chain levels compared to placebo by between 10-16%. Further, Clene reports that CNM-Au8 reduced mortality risk by 60%.

While these findings are, at first glance, positive, there are some concerns. First, the statistics above were honed through multiple statistical analyses and adjustments. Next, CNM-Au8 data heavily depends on exploratory analyses, which regulatory agencies are somewhat skeptical of. Finally, CNM-Au8 did not show significant benefits in slowing ALS progression when compared to a placebo.

Despite these difficulties, Clene plans on continuing CNM-Au8 development and running further studies.

Understanding Amyotrophic Lateral Sclerosis (ALS)

Also known as: Lou Gehrig’s disease

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that leads to nerve cell death in the spinal cord, brain stem, and brain. Normally, these neurons help the nervous system and motor neurons communicate, sending messages to muscles. ALS interrupts these messages. The muscles then weaken and waste. This condition is considered familial in around 5-10% of cases, meaning individuals have a genetic mutation connected to their ALS development. In the remaining 90-95% of cases, the cause is idiopathic, or unknown. This subtype is called sporadic ALS. ALS affects slightly more males than females and typically occurs in older individuals, though it can occur in people of all ages. Unfortunately, ALS progresses to the point of fatality, affecting movement, speech, and breathing. There is no cure, but some treatments can reduce symptoms.

Symptoms associated with amyotrophic lateral sclerosis can include:

• Muscle weakness, spasticity, and/or cramping
• Difficulty performing small movements or everyday tasks
• Increased reflexes
• Slowed or slurred speech
• Muscle atrophy
• Decreased muscle tone
• Frequent tripping and falling
• Difficulty speaking or swallowing
• Inappropriate or untimely crying or laughing
• Poor posture
• Inability to move muscles that gradually affects the entire body