NP-120 Eases Cough in IPF Patients, Top-line Data Show
Algernon Pharmaceuticals’ experimental oral therapy NP-120 (ifenprodil) significantly reduced coughing in people with idiopathic pulmonary fibrosis (IPF), according to a new analysis of top-line data from a proof-of-concept Phase 2a clinical trial.
The analysis showed the therapy was much more effective at easing cough than previously reported.
NP-120’s “potential as a potent cough treatment just increased,” Christopher J. Moreau, Algernon’s CEO, said in a press release. “We have to remember that cough in IPF patients has been historically even more difficult to treat than stand-alone chronic cough.”
In the Phase 2a clinical trial (NCT04318704) 20 people with IPF and persistent, hard-to-treat cough received NP-120 (20 mg, taken three times daily) for 12 weeks (about three months).
The study’s main goals were to assess how many patients achieved a 50% or greater drop in daily cough frequency, as assessed with a portable cough monitor, and of those showing preserved lung function, as measured by forced vital capacity (FVC).
FVC is a measure of lung function based on how much air an individual can forcibly exhale after a deep breath.
Previous top-line data showed the therapy was generally well-tolerated and that more than half of the patients (65%) had their FVC values stabilize or improve after 12 weeks of treatment. This was significantly different from the 40% of patients who were expected to experience no FVC decline if they were given a placebo, based on historical data.
In addition, 30% of participants showed a reduction of at least 50% in the mean number of coughs per hour over 24 hours by study’s end. The expected effect of a placebo was set at a responder rate of 25%, meaning that NP-120’s effects didn’t reach statistically significant differences.
Still, at the end of treatment, most participants (75%) showed reductions in cough and the median cough count per hour over 24 hours fell by 38%.
The new analysis, led by Jacky Smith, PhD, an expert on cough and Algernon’s lead scientific and medical advisor, reviewed data regarding the number of 24-hour coughs and coughs while awake after four and 12 weeks of treatment.
Calculating the coughs
Instead of the previously used arithmetic mean, the researchers now calculated the geometric mean of cough counts. The latter “is the standard method employed in trials measuring objective cough counts, where data are heavily skewed,” meaning they are not symmetric to the mean, Algernon stated in the press release.
The results showed that the geometric mean of coughs per hour over 24 hours fell by 32% after four weeks and by 39.5% after the 12-week treatment — a statistically significant difference when compared with study’s start.
A significant drop in the geometric mean awake cough counts also was seen both at four weeks (reduction of 30.2%) and 12 weeks (reduction of 37.4%).
“This additional analysis confirms my initial positive impression of the study,” said Smith, who is a professor of respiratory medicine at the University of Manchester, and an honorary consultant at Manchester University NHS Foundation Trust, in England.
NP-120 was developed initially by Sanofi for the treatment of circulatory disorders. It works by blocking N-methyl-D-aspartate NMDA-type subunit 2B, a receptor protein involved in a signaling pathway implicated in both cough and tissue scarring, two common features of IPF.
“The NMDA receptor has always been an interesting target for cough, but other agents have been poorly tolerated,” Smith said.
“The effects of this magnitude in an IPF population, where other drugs have failed to demonstrate a benefit, is notable, and I look forward to seeing the Company’s full data set next month,” Smith added.
Algernon is planning to request clearance from the U.S. Food and Drug Administration (FDA) for a Phase 2b trial to test a new, once-daily formulation of ifenprodil in people with IPF.
The company also plans to submit applications soon to the FDA requesting NP-120 (ifenprodil) be designated an orphan drug and breakthrough therapy. Both designations are meant to accelerate the therapy’s clinical development and regulatory review.