NP001 seen to extend survival, preserve lung function with ALS
Analysis, spanning years, of treated and placebo patients in Phase 2 trials
Neuvivo’s investigational therapy NP001 (sodium chlorite), designed to dampen inflammation and restore immune system balance, extended survival in people with amyotrophic lateral sclerosis (ALS), according to an combined analysis of data, spanning up to 11 years, on patients who took part in either of two Phase 2 clinical trials.
This survival benefit was particularly greater in adults up to age 65, and in people with moderate inflammation and low levels of creatinine, a marker for reduced muscle mass, prior to starting treatment.
Based on these data, Neuvivo recently filed an application with the U.S. Food and Drug Administration (FDA) seeking NP001’s approval for ALS.
“By restoring balance to the innate immune system of ALS patients, NP001 could be the first treatment that zeros in on a root cause of disease progression to slow loss of muscle function,” Michael McGrath, MD, PhD, co-founder and chief scientific officer at Neuvivo, said in a company press release.
Immune dysfunction, chronic inflammation factor in disease progression
The survival analysis was detailed in the study “The Effectiveness of NP001 on the Long-Term Survival of Patients with Amyotrophic Lateral Sclerosis,” published in the journal Biomedicines.
Immune dysfunction and excessive inflammation in the brain and spinal cord are among the many mechanisms involved in the progression of ALS, a neurodegenerative disease marked by the loss of muscle function, which impairs a person’s ability to walk, talk, eat, and eventually breathe.
NP001 is designed to reduce excessive inflammation by targeting innate immune cells called macrophages. Its goal is to reset these cells into a noninflammatory state, thereby lowering the activation of other immune cells and slowing ALS progression.
In the two clinical trials, a Phase 2a (NCT01281631) and a Phase 2b (NCT02794857) study (completed in 2012 and 2017, respectively), NP001 was given via intravenous, or into-the-vein, infusions over six months. Participants received infusions over three to five consecutive days each month, for 20 infusions in total.
Although early data indicated that NP001 failed to show benefits overall, the therapy did slow disease progression and preserved lung function in ALS patients with high levels of inflammation.
Best benefits seen when infusion treatment given at higher 2 mg/kg dose
The survival study now examined 268 patients, entering the Phase 2a and 2b trials at ages 80 and younger (mean age, 56), who were treated with NP001 or given a placebo for six months Each treated participant received at least one dose of NP001 at either 1 mg/kg or 2 mg/kg dose.
In the overall population, patients treated with the 2 mg/kg dose of NP001 lived a median of 4.8 months longer than those in the placebo group (2.7 vs. 2.3 years). Among patients 65 and younger, median survival extended to 10.8 months over placebo in the high-dose group (3.3 vs. 2.4 years). No differences were observed in the 1 mg/kg group or in older patients.
“Adding another year of life — to continue enjoying favorite activities and spending time with loved ones — could be tremendously impactful for people living with ALS and their families,” said Ari Azhir, PhD, founder and CEO of Neuvivo.
In another study, titled “Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression,” which was also published in Biomedicine, researchers reported survival and lung function data based on certain biomarker levels.
The analysis specifically focused on patients with moderate levels of inflammation at the study’s start (baseline), as indicated by the blood levels of C-reactive protein (CRP) above 1.13 milligrams per liter and low creatinine levels. While creatinine levels are often used as a marker of kidney function, low creatinine levels also can reflect ongoing inflammation due to CRP consuming muscle mass.
Among these patients, median overall survival was extended by 17.1 months in those treated with a 2 mg/kg NP001 dose, compared with patients given a placebo (45.5 vs. 28.4 months). Moreover, this treated group of patients had a 46.7% slower rate of lung function decline.
Trials’ findings support potential to put immune system ‘back into balance’
“The current study reports, for the first time, that the diseased innate immune system can be put back into balance, allowing, in the case of ALS, almost a year and a half in extended survival after just six months of intermittent therapy,” the researchers concluded.
“In addition to the new data suggesting an extended survival benefit for people aged 21-65, NP001 is also the first ALS treatment that has been shown to preserve lung function, a major cause of morbidity and mortality in ALS patients,” McGrath said.
The FDA previously granted NP001 orphan drug and fast-track designations for ALS, which the company can leverage to shorten the time taken for an approval decision by the agency.
“We will continue to work closely with the FDA throughout the review process to move NP001 toward a potential regulatory approval as quickly and efficiently as possible,” said Matthew Davis, MD, chief medical officer of Neuvivo.
About the Author
