NP001 Slows ALS Progression in Middle-aged Patients With Inflammation

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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NP001 slowed functional and lung declines in a subset of middle-aged patients with amyotrophic lateral sclerosis (ALS) who had high levels of inflammation, according to an analysis of previous data from Phase 2a and 2b clinical trials.

While earlier results failed to show overall success of NP001 — Neuvivo’s experimental ALS treatment — this new analysis identifies a subset of patients ages 40–65 who might benefit from the therapy.

“It was clear to us that we needed to re-analyze the data from the earlier trials and in doing so we identified a large subset of patients who experienced benefits from treatment with NP001,” Ari Azhir, PhD, founder and CEO of Neuvivo, said in a press release.

The study, “Phase 2B randomized controlled trial of NP001 in amyotrophic lateral sclerosis: pre-specified and post-hoc analyses,” was published in Muscle and Nerve.

Inflammation is a key contributor to ALS progression. NP001, first developed by Neuraltus Pharmaceuticals, targets a set of immune cells called macrophages, helping to reduce their activation and reset them to a non-inflammatory state.

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Data from a Phase 2a trial (NCT01281631) suggested that NP001 might slow disease progression, especially in patients with high levels of C-reactive protein (CRP), an indicator of systemic inflammation.

A Phase 2b trial (NCT02794857) was designed to validate those findings in 138 ALS patients with high CRP levels, those above 1.13 milligrams per liter (mg/L), but failed to meet its primary and secondary endpoints. Specifically, into-the-vein infusions of NP001 over a six-month period did not overall slow physical functional or lung function declines in treated patients.

The researchers observed, however, that all patients in the NP001 groups from both trials who showed no functional disease progression — meaning they experienced no change in ALS Functional Rating Scale-Revised (ALSFRS-R) scores over the six-month period — were ages 40 to 65.

This finding suggested that NP001 may be particularly effective among patients in this age group who also had high CRP levels, the researchers hypothesized.

To test that premise, the team performed a combined analysis of the data from a subset of 117 patients enrolled in the Phase 2a and 2b trials who were ages 40–65 and had high CRP levels.

In this group, those treated with NP001 showed a 36% overall slower decline in ALSFRS-R scores than those who were given placebo, indicating that NP001 treatment can slow disease progression in these patients.

Furthermore, patients with higher CRP levels at the start of the study (baseline) were more likely to benefit from treatment. Among patients with CRP levels above 3 mg/L at baseline, those who received NP001 were 10 times more likely not to show disease progression than those in the placebo group.

These results are consistent with NP001’s anti-inflammatory actions. Future studies of other inflammatory markers in these patients’ blood samples may help to explain how NP001 slows disease progression, the researchers noted.

NP001-treated participants also had a 51% slower loss of vital capacity, indicating a diminished decline in lung function compared with placebo.

“Beyond the valuable effects on a patient’s overall disease manifestation, there was another even more important effect on preservation of vital capacity,” said Robert Miller, MD, medical director of the Forbes Norris ALS Research Center at the California Pacific Medical Center in San Francisco.

“This is key from a clinical perspective and is the first time any drug has had an effect on vital capacity. This effect alone is very supportive of NP001 use in ALS patients, as it should provide a longer lifespan for ALS patients who respond,” Miller said.

Since the trials were not designed originally for these analyses, future studies will need to be aimed specifically at validating these findings, the team noted.

“This Phase 2 post hoc analysis [of previous data] is welcome progress in the development of new and much needed ALS treatments,” said Merit Cudkowicz, MD, investigator in the Phase 2 studies, co-founder of the northeast ALS consortium, director of the Healey and AMG Center for ALS, and professor of neurology at Harvard.

“This will inform future studies of NP001 in people with ALS,” Cudkowicz said.