Background
NP001 is a small molecule first developed by Neuraltus Pharmaceuticals and currently owned by Neuvivo. The proposed mechanism of action of NP001 is to modulate macrophages within the innate immune system, aiming to restore balance and reduce uncontrolled inflammation. By targeting inflammation, this approach seeks to slow disease progression and preserve muscle function and is currently being evaluated as a potential treatment for ALS/MND. To date, NP001 has undergone one Phase I and two Phase 2 trials for safety and tolerability evaluation. All studies were run in North America.
Trial Design & Results
In 2010 a randomized, double-blind placebo-controlled Phase 1 clinical trial was run by Neuraltus Pharmaceuticals to evaluate safety and tolerability of single ascending doses of NP001. The study enrolled 32 people living with ALS/MND in three sites within the US. The study showed that all doses of NP001, administered by 30 min infusions, were safe and generally well tolerated (Miller et al., 2014).
Based on these results, Neuraltus Pharmaceuticals initiated two Phase 2 trials. The first Phase 2 trial (Phase 2A) ran from 2011 to 2012 and it was a multicenter, randomized, double blind placebo-controlled trial that enrolled 136 people living with ALS/MND. Participants received 2mg/kg, 1mg/kg or placebo for 6 months, through intravenous infusions. The study showed that the treatment was safe and well tolerated at all doses, with some pain at the injection site and dizziness being the most common side effects. No significant overall slowing of disease was observed in any of the groups. A post hoc analysis showed that a subset of participants with evidence of elevated systemic inflammation treated with the higher dose of NP001 showed some potential benefit, however, the trial was underpowered to make any claim regarding NP001 efficacy (Miller et al., 2015).
Building on this data, a second Phase 2 trial (Phase 2B) was run from 2016 to 2017 and it was a randomized, double-blind, placebo-controlled study of NP001 in people living with ALS/MND who also showed evidence of elevated systemic inflammation. A total of 138 participants within 3 years of symptom onset were enrolled and randomized at a 1:1 ratio NP001 (2mg/kg) to placebo. The clinical trial found that the drug was safe and well tolerated, however, it found no difference in the primary (ALSFRS-R) or secondary (vital capacity) endpoints over six months (McGrath et al., 2023). Following these results, Neuraltus Pharmaceuticals went out of business.
In 2019, Neuvivo obtained the chemical manufacturing, toxicology, and clinical records related to NP001 from Neuraltus Pharmaceuticals (McGrath et al., 2023). In 2023, Neuvivo carried on a post hoc analysis on the phase 2B trial that showed some effect on respiratory vital capacity in a small subgroup of people who participated in the trial, however, the study was largely underpowered (McGrath et al., 2023). Furthermore, an analysis on long-term survival was conducted for participants of both phase 2 trials. The study highlighted that people who took part in both phase 2 clinical trials, showed some benefit if under the age of 65 and treated with 2mg/kg of NP001 (Forrest et al., 2024).
In October 2024, on the basis of these post hoc analysis, Neuvivo submitted a new drug application (NDA) to the U.S. Food and Drugs Administration (FDA) seeking approval for NP001 for the treatment of ALS/MND. Following meetings with the FDA, Neuvivo are now planning a pivotal Phase 3 study with commencement in 2026.
Summary
NP001 is a molecule that aims to modulate systemic inflammation in people living with ALS/MND. Historically, this has been a very controversial pathway to link to neurodegeneration and a hard one to target. Results from the presented trials show weak indications that NP001 could have marginal benefits in younger people living with ALS/MND with a heightened inflammatory profile. However, it is the opinion of the SAC that the data currently publicly available is not sufficient to determine whether NP001 has any effect on disease progression. The SAC encourages Neuvivo to be mindful in stating NP001’s effectiveness in slowing disease progression until clear evidence demonstrates its impact on people living with ALS/MND.
International Alliance of ALS/MND Associations
April 2026
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