A Phase 2 clinical trial which sought to evaluate the safety, efficacy, and tolerability of NP-120 (ifenprodil) for idiopathic pulmonary fibrosis (IPF) had some surprising results. Initially, the study was designed to be a proof-of-concept study. 20 patients with IPF and a chronic cough enrolled. After being treated, shares Pulmonary Fibrosis News, researchers found that NP-120 was able to either stabilize or improve overall lung function. Additionally, the treatment was helpful in reducing the chronic cough. 

Evaluating NP-120

According to Algernon Therapeutics, NP-120 (ifenprodil) was initially developed by Sanofi in the 1990s to treat various circulatory disorders. However, after discovering that NP-120 reduced fibrosis (scarring) in animal models of IPF at a rate greater than the current standards-of-care, NP-120 was able to be repurposed as a potential human IPF treatment. Overall, Algernon Therapeutics describes NP-120 as:

an N-methyl-d-aspartate (NDMA) receptor glutamate receptor antagonist specifically targeting the NMDA-type subunit 2B (Glu2NB). Ifenprodil also exhibits agonist activity for the Sigma-1 receptor, a chaperone protein up-regulated during endoplasmic reticulum stress.

The NP-120 Clinical Trial

In this particular study, participants received 20mg NP-120 3x each day for a 12-week period. Findings include:

• 65% of trial participants saw the stabilization or improvement of forced vital capacity (FVC), which measures overall lung function. Additionally, 75% of patients experienced an improvement in their chronic cough. 
• C3M, C6M, and ELP-3 are all blood biomarkers that correlate to worse patient outcomes. While NP-120 did reduce the number of these markers, the reduction was not considered to be statistically significant. 
• NP-120 was relatively safe and well-tolerated. Adverse reactions included appetite loss and digestive problems. 

Moving forward, Algernon Therapeutics expects to share additional trial data in August 2022. Additionally, they hope to be able to begin an additional Phase 2b study in the future that would evaluate a once-daily administration – rather than the three required in the study – of NP-120. 

Idiopathic Pulmonary Fibrosis (IPF): An Overview

So what exactly is idiopathic pulmonary fibrosis (IPF)? If you break down the name, you’ll see that it’s the hardening (fibrosis) or scarring of lung tissue (pulmonary) from an unknown cause (idiopathic). Because IPF is idiopathic, doctors are not sure what contributes to the formation of this scar tissue. However, some experts theorize that some people have a genetic susceptibility to IPF; others believe that potential triggers such as cigarettes, viral infections, or exposure to metal or wood dust may play a role. As the fibrosis occurs, adequate oxygen is unable to enter the bloodstream, contributing to some of the condition’s symptoms. Symptoms can include:

• A dry, hacking cough
• Shortness of breath
• Appetite loss
• Gastroesophageal reflux disease (GERD)
• Blood clots in the lungs
• Clubbed fingers and toes
• Increased risk of pneumonia and lung cancer

Unfortunately, IPF also comes with a poor prognosis, with a survival rate of 3-5 years following diagnosis. However, with new treatments and research, this may change in the future.