PRM-151 Seen to Slow Decline in Lung Function of IPF Patients in Phase 2 Trial

Results of a Phase 2 trial of Promedior’s PRM-151, a treatment candidate for idiopathic pulmonary fibrosis (IPF), show a slowing in the loss of lung function among treated patients.

The research, “Effect of Recombinant Human Pentraxin 2 vs Placebo on Change in Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis: A Randomized Clinical Trial,” was published in the journal JAMA.

Epithelial damage and abnormal wound repair contribute to IPF development. Fibrocytes, cells derived from peripheral blood monocytes (a type of white blood cell), have been implicated in this process.

Pentraxin 2 is a plasma protein that works to resolve fibrosis by stopping monocytes from differentiating into macrophages and stopping the production of TGF-β1, an inflammatory molecule. Patients with IPF have lower than usual plasma concentrations of pentraxin 2, which correlates with disease severity.

PRM-151, an engineered human form of pentraxin 2, was seen in preclinical animal tests to reduce lung fibrosis for 30 days. Results from a Phase 1 trial in healthy participants and PF patients also showed that PRM-151 significantly increased blood levels of the body’s own pentraxin 2. Results of a separate Phase 1 study in IPF patients also demonstrated improvements in forced vital capacity (FVC) — a measure of lung function — and in the six-minute walk distance (6MWD) – a test of exercise capacity – following treatment with PRM-151.

A double-blind, multi-center Phase 2 clinical trial (NCT02550873) was undertaken to further examine PRM-151’s efficacy and safety relative to placebo.

The study, also known as PRM-151-202, enrolled 117 IPF patients, ages 40-80 years, with predicted percentage of normal FVC value (FVC %) of 50-90%. (Of note, abnormal FVC % values are often defined as less than 80% or greater than 120% of the predicted value.)

Patients also had a forced expiratory volume in the first second (FEV1)/FVC ratio — which represents the percent of the lung size of air that can be exhaled in one second — above 0.70, and were able to walk 150 meters or more in the 6MWD test.

Treatment with the approved IPF therapies Ofev (nintedanib, Boehringer Ingelheim) or Esbriet (pirfenidone, Genentech) was reported by 87% of patients.

A total of 116 patients (mean age of 68.6 years) received at least one intravenous dose of PRM-151, and 111 completed the study.

Results revealed that, compared to placebo, treatment with PRM-151 every four weeks led to a slower decline in lung function over 28 weeks, as measured by the mean change in FVC% (-2.5 versus -4.8 in the placebo group).

No differences were found in total lung volume, interstitial lung abnormalities, or diffusing capacity for carbon monoxide — an indication of how much oxygen travels from the lungs to the blood stream.

PRM-151 also led to significantly better exercise capacity, as assessed by 6MWD, compared to placebo, which suggests “a potential benefit for overall functional decline,” the researchers wrote.

The most frequent adverse events in patients treated with PRM-151 compared to those taking placebo were cough (18% vs 5% in the placebo group), fatigue (17% vs 10%), and nasopharyngitis, or cold (16% vs 23%). No serious adverse events were related to the study medication.

“In this preliminary study, infusions of recombinant human pentraxin 2 vs placebo resulted in a slower decline in lung function over 28 weeks for patients with idiopathic pulmonary fibrosis. Further research should more fully assess efficacy and safety,” the researchers concluded.