ALS: Phase 2 Clinical Trial for NP001 Shows Possible Benefit

by Amy Madsen on Mon, 2012-11-05 05:00

The experimental drug NP001 slowed or halted disease progression in some trial participants with ALS; a phase 3 trial is planned for 2013

Article Highlights:
  • NP001 was safe and well-tolerated in a phase 2 study that included 136 people with ALS.
  • Results showed a slowing or halting of disease symptoms in some participants during the six-month trial; however, the results didn't reach statistical significance until data were added from people with ALS who took placebos in other trials.
  • Neuraltus Pharmaceuticals is hoping to open a phase 3 trial of NP001 in 2013.
Update (Dec. 12, 2013): In a Dec. 9, 2013, press release, Neuraltus reported that NP001 treatment in the phase 2 trial showed positive trends in slowing ALS progression and that the data support the hypothesis that NP001's primary mechanism of action is restoration of normal function of macrophages. The findings were presented at the 24th International Symposium on ALS/MND in Milan, Italy. Neuraltus recently updated their development timeline for NP001, noting that it is now expecting to start a phase 3 trial some time in 2014, rather than 2013.

Results from a completed phase 2 trial of the experimental therapy NP001 in people with amyotrophic lateral sclerosis (ALS) show that in some trial participants, the drug appeared to be effective at slowing or stopping progression of the disease.

The results are "encouraging," said the trial's principal investigator, Robert Miller of California Pacific Medical Center in San Francisco, in a press release, noting that halting or slowing the rate of disease progression "would translate into a clear clinical benefit" for a subset of people with the disease.

Based on the trial results and after a meeting with the U.S. Food and Drug Administration (FDA), the drug’s developer, biopharmaceutical company Neuraltus Pharmaceuticals of Palo Alto, Calif., says it is planning a phase 3 clinical trial program for the drug that is expected to begin in 2013.

A small molecule drug, NP001 targets immune system cells called macrophages in the blood and microglia in the central nervous system, causing them to switch from an active "attack" mode to a "protective" mode. A growing body of evidence points to malfunction of the immune system as at least part of the ALS disease process.

Phase 2 trial assessed safety and function

In the multicenter, double-blind, placebo-controlled phase 2 trial of NP001, 136 people with ALS were randomly selected to receive the drug at either 1 milligram per kilogram of body weight or 2 milligrams per kilogram of body weight, or a placebo (inactive substance). Treatment was administered via intravenous infusion over a period of six months, after which participants went through a six-month follow-up period.

The trial was designed to:

  • assess safety and tolerability;
  • detect biological markers (biomarkers) associated with inflammation; and
  • evaluate changes in each participant's ALS Functional Rating Score-Revised (ALSFRS-R), a ratings scale used by physicians to assess symptom progression in individuals with ALS.

‘Trends’ toward slower and halted disease progression

NP001 was found to be safe and well-tolerated.

When the investigators looked at the efficacy of NP001, they found "trends" toward slower disease progression in the treated group compared to the placebo group. However, the difference in disease progression rates between treated and untreated trial participants reached statistical significance only when the NP001 group was compared to placebo groups from both this trial (concurrent placebo group) and from earlier ALS trials (historical placebo group).

Analysis of disease progression results showed that higher doses of NP001 were associated with greater positive effects. Of those who received the 2-milligram-per-kilogram dosage of NP001, 27 percent had no disease progression during the six-month treatment period — 2.5 times as many as had no disease progression in the concurrent placebo group. When data were added in from the historical placebo group, the results were even more robust and became statistically significant.

Results from a phase 1 trial announced in 2010 showed NP001 to be safe and well-tolerated at four different dose levels when given as a single intravenous treatment to people with ALS. There was also a statistically significant improvement in blood levels of a biomarker thought to be involved in ALS disease progression.

For more information on this phase 2 trial, see A Study of NP001 in Subjects with Amyotrophic Lateral Sclerosis (ALS); or enter NCT01281631 into the search box at

In addition, Neuraltus has a toll-free number for patients and physicians who have questions about the study. Call (888) 347-7799 through Dec. 31, 2012.

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