Neuvivo requests FDA approval of ALS treatment NP001
Company says therapy could be disease-modifying
Neuvivo has filed an application with the U.S. Food and Drug Administration (FDA) requesting the approval of its investigational therapy NP001 (sodium chlorite) to treat amyotrophic lateral sclerosis (ALS).
The new drug application comes on the heels of combined data from Phase 2a (NCT01281631) and Phase 2b (NCT02794857) clinical trials, in which NP001 slowed disease progression and preserved lung function in a subset of ALS patients with high levels of inflammation.
If approved, NP001 could be the first disease-modifying therapy for ALS designed to restore the balance of the innate immune system to ease the uncontrolled inflammation that contributes to disease progression, according to the company.
The FDA previously granted NP001 orphan drug and fast track designations, making the drug eligible for accelerated approval and priority review, which could shorten the time to potential approval.
“We are thrilled to have submitted NP001 for FDA approval as the treatment platform may substantially preserve lung function … especially in patients identified through therapeutic biomarkers as having underlying, uncontrolled inflammation as a result of ALS,” Ari Azhir, PhD, founder and CEO of Neuvivo, said in a company press release.
Reducing inflammation by targeting immune cells
ALS is a neurological disorder caused by progressive damage to motor neurons, the nerve cells responsible for voluntary movement, leading to worsening muscle weakness that manifests as trouble moving around and difficulty speaking and swallowing. When muscles in the chest and abdomen weaken, often during the later stages of the disease, the disease also leads to breathing difficulties.
There are many mechanisms involved in the progression of ALS, including inflammation. NP001 is designed to reduce the excessive inflammation that’s observed in most ALS patients by targeting immune cells called macrophages. The goal is to reverse the activation of these cells into a non-inflammatory state, which is expected to have a cascade effect and reduce the activation of other immune cells.
Neuvivo believes that through this mechanism NP001 could restore balance to the immune system, slowing the progression of ALS and preserving skeletal muscle function, including the diaphragm.
In the two Phase 2 clinical trials, NP001 was administered via intravenous, or into-the-vein, infusions over six months. Each month, patients received infusions over three to five consecutive days, for a total of 20 infusions.
While earlier clinical trial results failed to show overall success of NP001, additional analyses identified a particular subset of patients, ages 40-65, with high levels of C-reactive protein, a marker of systemic inflammation, for whom the therapy may be beneficial.
When examining combined data from the 117 middle-aged patients with systemic inflammation who participated in the Phase 2a and Phase 2b trials, researchers found that NP001-treated participants had a 36% slower decline in their ALS Functional Rating Scale-Revised (ALSFRS-R) scores over the six-month period compared with the placebo group, indicating slower disease progression.
Participants in this group who received NP001 also experienced a 51% slower decline in their lung function, as assessed with the percentage predicted vital capacity.
Additional biomarker analyses from Phase 2a trial participants indicated that NP001 limited the leak of gut bacteria into the bloodstream and reduced the levels of inflammatory markers.
“Based on the evidence shown across the Phase 2a, Phase 2b, and … the biomarker analysis, we believe submitting the New Drug Application to the FDA for NP001 offers great promise to the ALS community,” said Matthew Davis, MD, chief medical officer of Neuvivo.
The submission “brings new hope to people living with ALS, their families and caregivers,” said Namita Goyal, MD, professor of neurology at the University of California, Irvine.
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