New data from Phase 2 clinical trials indicate that NP001 (sodium chlorite) is associated with a significant survival benefit in a subset of amyotrophic lateral sclerosis (ALS) patients who did not show signs of disease progression during treatment. The findings, presented at the ALS Network Research Summit, suggest a potential breakthrough in addressing respiratory decline, a major cause of mortality in ALS patients.
Survival Extension in Non-Progressors
In this group of non-progressors, those given NP001 for six months lived 22 months longer than individuals in the control group, most of whom were receiving riluzole, an approved ALS therapy. Neuvivo, the therapy developer, believes the survival extension is related to the treatment’s demonstrated ability to slow respiratory declines.
"Data consistently demonstrate that NP001 slows or halts ALS progression in a subset of patients with an inflammatory form of the disease after only six months of treatment," stated a company press release. These findings align with recently published analyses from a larger group of trial participants, supporting Neuvivo’s application to the U.S. Food and Drug Administration (FDA) for NP001 approval.
Mechanism of Action and Previous Trial Data
ALS is a complex neurodegenerative disease characterized by the death of nerve cells controlling voluntary movements, leading to progressive loss of function and eventual respiratory failure. Inflammation and immune cell dysfunction are believed to contribute to neurodegeneration in ALS.
NP001, administered intravenously, aims to reprogram immune cells called macrophages from a toxic, proinflammatory state to a noninflammatory state. This is expected to suppress uncontrolled immune responses that drive inflammation and nerve cell damage, thereby slowing disease progression.
NP001 was previously tested in two placebo-controlled Phase 2 clinical trials. While initial results did not show a significant slowing of disease progression as assessed by the ALS Functional Rating Scale Revised (ALSFRS-R) in the overall study population, further analyses indicated the treatment could slow disease progression and preserve lung function in a subset of middle-aged patients with high levels of inflammation.
Impact on Lung Function and Disease Progression
Michael McGrath, MD, PhD, Neuvivo’s founder and chief scientific officer, presented additional analyses at the summit, focusing on the subset of patients who were considered nonprogressors. Among these patients, NP001 treatment at the 2 mg/kg dose was associated with a significant slowing of lung function declines compared with the placebo.
Moreover, among patients considered to have risk characteristics for disease progression based on natural history studies, 31% of NP001-treated patients showed no disease progression over six months compared with 14% of those given the placebo.
The median overall survival for NP001-treated patients was 58 months, compared with 36 months in the control group, representing a significant, nearly two-year survival benefit. Clinical improvements in nonprogressors were accompanied by a correction of inflammatory biomarkers and reductions in neurofilament light chain, a biomarker of nerve damage.
Addressing Unmet Needs in ALS Treatment
Neuvivo believes the data further support the idea that slowing respiratory declines is critical for improving ALS survival. Currently, there are no therapies available that can preserve breathing function in ALS patients. If approved, NP001 would be the first disease-modifying treatment able to do so.
