New ALS trial data show nearly 2-year survival benefit with NP001
Longer survival demonstrated in subset of patients in 2 Phase 2 trials
NP001 (sodium chlorite) was associated with a significant survival benefit among a subset of amyotrophic lateral sclerosis (ALS) patients who did not show signs of disease progression when treated with the investigational therapy in Phase 2 clinical trials, according to new data from the two studies.
In this group of so-called nonprogressors, those given NP001 for six months lived 22 months longer than individuals in the control group, most of whom were receiving the approved ALS therapy riluzole. Therapy developer Neuvivo believes the survival extension is related to the treatment’s demonstrated ability to slow respiratory declines, according to a company press release.
“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,” the release stated.
These findings are consistent with recently published analyses from a larger group of trial participants, the company noted. Those analyses backed Neuvivo’s application last year to the U.S. Food and Drug Administration (FDA) seeking approval of NP001 for ALS.
The new data were presented at the ALS Network Research Summit, held earlier this month in San Francisco, by Michael McGrath, MD, PhD, Neuvivo’s founder and chief scientific officer.
Ari Azhir, PhD, CEO and also a founder of Neuvivo, noted that the new findings “align well” with the other data published last fall, and “add to the body of evidence supporting the clinical benefits of NP001 to treat ALS.” Azhir added that “this drug may offer substantial benefit to people living with ALS.”
NP001 was tested against a placebo in 2 earlier clinical trials
ALS is a complex neurodegenerative disease in which the nerve cells responsible for controlling the body’s voluntary movements die off. This leads to a progressive loss of daily functions including walking, eating, and talking. An eventual loss of breathing function is the most common cause of death for patients.
Among the factors believed to contribute to neurodegeneration in ALS are inflammation and immune cell dysfunction.
NP001, given intravenously, or via infusions into the bloodstream, aims to reprogram immune cells called macrophages from a toxic, proinflammatory state to a noninflammatory state. Ultimately, this is expected to suppress uncontrolled immune responses that drive inflammation and nerve cell damage in ALS, thereby slowing disease progression.
The treatment candidate was previously tested in two placebo-controlled Phase 2 clinical trials — a Phase 2a study (NCT01281631) and a Phase 2b study (NCT02794857) — involving ALS patients, ages 21-80, whose symptoms had started in the prior three years. One of two doses of NP001 (1 mg/kg or 2 mg/kg) or a placebo were given in monthly cycles, with infusions administered over 3-5 consecutive days, during a six-month treatment period.
Results from the studies showed that NP001 did not significantly slow disease progression relative to the placebo, as assessed by the ALS Functional Rating Scale Revised (ALSFRS-R). However, additional analyses indicated the treatment could slow disease progression and preserve lung function in a subset of middle-aged patients with high levels of inflammation.
Neuvivo then published two more studies in October last year that further examined long-term survival outcomes in patients who had previously been treated in the six-month clinical trials.
Those findings showed that survival was significantly extended — by 4.8 months — in patients who had received NP001 at the 2 mg/kg dose as compared with those given the placebo. Moreover, an even more pronounced benefit was found for patients who were 65 or younger at trial enrollment, and among those with moderate levels of inflammation.
Treatment with NP001 also was associated with about a 50% slowing of respiratory declines, which Neuvivo believes contributed to the survival advantage.
New data show therapy slowed lung function declines in certain patients
In the summit presentation, McGrath shared the findings of additional analyses that expanded on these results. These new data focused specifically on the subset of patients who were considered nonprogressors — meaning they had not experienced a worsening of ALSFRS-R scores — during the Phase 2 trials.
“One of the most confounding aspects of ALS research is that this disease does not uniformly progress,” said McGrath, also an emeritus professor of medicine at the University of California San Francisco. “My analysis looked at patients whose progression slowed or halted using a standard test for functional change in ALS patients.”
Among these nonprogressors, 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.
One of the most confounding aspects of ALS research is that this disease does not uniformly progress. … [This] analysis looked at patients whose progression slowed or halted using a standard test for functional change in ALS patients.
The median overall survival for NP001-treated patients was 58 months, or nearly five years, compared with 36 months, or three years, in the control group. Overall, that amounted to a significant, nearly two-year survival benefit with the treatment.
Among nonprogressors, clinical improvements were accompanied by a correction of inflammatory biomarkers and reductions in neurofilament light chain, a biomarker of nerve damage, according to the company.
Neuvivo believes the data lend further support to the idea that slowing respiratory declines is critical for improving ALS survival.
The company noted that there are no therapies currently available that can preserve breathing function in ALS patients. If eventually approved, NP001 would be the first disease-modifying treatment able to do so, according to Neuvivo.
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