Most idiopathic pulmonary fibrosis (IPF) patients treated with NP-120 (ifenprodil) in a 12-week clinical trial saw their lung function improve or stabilize, and most also experienced an easing in coughing, according to top-line data announced by the therapy’s developer, Algernon Pharmaceuticals.
“Simply put, the IPF data is better than we could have imagined,” Christopher J. Moreau, Algernon’s CEO, said in a company press release.
A larger and placebo-controlled trial is being planned.
The proof-of-concert Phase 2 clinical trial (NCT04318704) enrolled 20 people with IPF and chronic cough, all of whom were treated with NP-120 (20 mg, taken three times daily) for 12 weeks, or about three months.
Its main goals were to assess the impact of treatment on forced vital capacity (FVC) — a measure of lung function based on how much air an individual can forcibly exhale after a deep breath — and on cough frequency, as measured by a monitor worn by study participants.
FVC stabilizes or improves with IPF treatment
Of the 20 patients, 13 (65%) saw their FVC values stabilize or improve after 12 weeks of treatment. Historical data suggest that, if the patients were given a placebo, about 30–40% would show no decline in FVC after 12 weeks. Compared with an expected placebo effect of 40%, the 65% responder rate seen with NP-120 was considered statistically significant.
A number of blood markers that are usually associated with worse outcomes in IPF, including proC3, C3M, C6M, reC1M, proC8, and ELP-3, tended to decrease with NP-120 treatment, though these trends did not reach statistical significance.
“The IPF data looks quite good. I was very surprised to see the data achieve statistical significance with such a small study size, when you consider the original goal of the study was to try to identify a signal,” said Martin Kolb, MD, PhD, a professor of respirology at McMaster University.
“I am confident that the Company should begin planning a sufficiently powered Phase 2b study to investigate [NP-120] as a possible new treatment for IPF patients, including those who have associated cough,” Kolb added.
In terms of chronic cough, 30% of study participants saw a reduction of at least 50% in their average number of coughs per hour over 24 hours by the study’s end. This was not statistically different from an expected placebo effect responder rate of 25%.
Still, most participants (75%) showed improvements in cough over 12 weeks on NP-120. Notably, the median cough count per hour over 24 hours fell by 38% after 12 weeks of treatment, Algernon reported.
“These data are quite compelling. Although the primary cough endpoint does not reach statistical significance, the reductions in cough counts, particularly the median cough counts, are suggestive of a beneficial effect. Furthermore, the choice of a 25% response rate as a comparator may understate the benefit,” said Jacky Smith, PhD, a professor of respiratory medicine at the University of Manchester.
“Existing IPF therapies have little to no effect on cough, and so coupled with the results in IPF seen in this trial, there is great reason for optimism. I am working with the Company to further analyze the data and encourage them to continue to study the effects on cough as development of this drug continues,” Smith added.
The active ingredient in NP-120, ifenprodil, was originally developed by Sanofi to treat circulatory system disorders, and it has been used in Japan for decades to treat vertigo. Consequently, the therapy’s safety profile is well-established.
This trial is a first for ifenprodil in people with IPF, and no new safety signals were observed. Just under half of its participants (45%) reported any treatment-emergent side effect, most of which were mild in intensity. The most common were digestive issues (25%) and decreased appetite (10%). One person withdrew from the study due to a tumor that was unrelated to the investigational treatment.
Full trial data are expected to be released next month, according to Algernon, and study results will be discussed at the 21st International Colloquium on Lung and Airway Fibrosis, set for October in Reykjavik, Iceland.
Larger Phase 2b study planned
Algernon is planning to start the process of asking the U.S. Food and Drug Administration (FDA) for the go-ahead to launch a Phase 2b study that would test a new, once-daily formulation of ifenprodil in people with IPF. Meanwhile, the company already asked for permission to test the therapy in patients with chronic cough and received positive feedback.
“While the cough data is also promising, we will wait until we have the full data set before making any final decisions on pursuing both IPF and chronic cough in separate Phase 2b clinical studies, or focussing on just IPF patients with associated cough,” Moreau said.
The company also plans to soon file applications to the FDA requesting NP-120 be designated an orphan drug and breakthrough therapy. Both designations are meant to speed the development and regulatory review of therapies aiming to treat serious conditions for which there is a high unmet need.