공고 • Jul 19
Algernon Pharmaceuticals Hits Co-Primary Endpoint in Its Phase 2 Study of Ifenprodil for Idiopathic Pulmonary Fibrosis and Chronic Cough
Algernon Pharmaceuticals Inc. announced positive topline data showing that it has met the co-primary endpoint in its Phase 2 proof of concept study evaluating NP-120 (“Ifenprodil”) for the potential treatment of idiopathic pulmonary fibrosis (“IPF”) and chronic cough. In the study, 65% of patients had stable or improved forced vital capacity (“FVC”) over the 12-week treatment period with statistical significance when compared to an anticipated placebo effect of 40%. FVC is the amount of air that can be forcibly exhaled from one’s lungs after taking the deepest breath possible. Ifenprodil is an N-methyl-D-aspartate (NMDA) receptor antagonist specifically targeting the NMDA-type subunit 2B (GluN2B), which prevents glutamate signalling. Ifenprodil represents a novel first in class treatment for both IPF and chronic cough. To understand the potential efficacy for Ifenprodil in IPF patients, lung function in this trial was measured by FVC (a best-efforts measurement) which was taken for each patient at baseline, and then again at 12 weeks. Patients whose FVC declined were classified as non-responders, while those whose FVC improved or remained stable were classified as responders. The primary endpoint of the IPF part of the study was the proportion of patients who responded. Of the 20 patients who enrolled, 13 (65%) had stable or improved FVC over the 12-week treatment period with statistical significance when compared to an anticipated placebo effect of 40% (p=.0225, 95% CI 40.8 to 84.6%, all numbers are Intent-to-Treat analysis). Importantly, key opinion leaders advising the company, as well as historical data on previously conducted IPF clinical studies(1), indicated that approximately 30-40% of patients IPF patients would experience no decline in FVC if they were dosed with a placebo over the 12-week period, demonstrating that Ifenprodil showed promising initial IPF efficacy in this trial. The Company also reports trends to reduction in many of the serum markers that were tested including proC3, C3M, C6M, reC1M, proC8 and ELP-3, although the data did not reach statistical significance. Elevation of these markers has been associated with increased mortality and risk of disease progression in previous research studies. or the chronic cough part of the study’s primary endpoint, 30% of subjects achieved the endpoint of a 50% reduction in the average number of coughs per hour over 24 hours from baseline to week 12. While this primary cough study endpoint did not achieve statistical significance when compared to an anticipated placebo effect of 25%, the secondary endpoint of actual changes (reduction) in cough counts did. Specifically, subjects experienced a 24% relative reduction from baseline in mean cough count, and a 38% relative reduction from baseline in median cough count in their 24-hour cough count per hour at week 12 (p=0.0344). In addition, 75% of subjects saw improvements in their cough over 12 weeks. This data shows that while Ifenprodil didn't achieve the more stringent primary endpoint parameter on cough, there is a definite signal (effect) when comparing cough counts directly to their baseline measurement. Furthermore, in contrast with recent studies on cough drugs targeting purinergic receptors, the observed effect may not be dependent on a subject’s baseline cough count; in a subgroup analysis, subjects with baseline cough counts below the median for the study appeared to achieve similar reductions in relative cough count to those with baseline counts above the median. The results also show that Ifenprodil’s safety profile in this trial was consistent with findings from previous studies of the drug, with no new safety signals observed. 45% of subjects experienced at least one treatment-emergent adverse events (TEAE), most of which were mild in intensity. The most common TEAE’s were gastrointestinal disorders (25%) and decreased appetite (10%). One participant withdrew from the study due to a hepatic neuroendocrine tumour unrelated to Ifenprodil, that resulted in death. Although Ifenprodil has been used in Japan for decades to treat vertigo, this is the first study in an IPF population, and so the Company reported that no new safety concerns were identified. The Company expects to receive the full data set from the study in August 2022 and will present the full results of the study at the 21st International Colloquium on Lung and Airway Fibrosis in Reykjavik, Iceland in October 2022. Based on the positive data, the Company plans to file a pre-IND application with the U.S. FDA for a Phase 2b IPF study. The current plan would be to switch to a new once-a-day formulation of Ifenprodil from the 3-times daily dosing currently being used. The Phase 2b study will also have multiple arms, multiple doses, would be placebo controlled and would be double blinded and randomized. For chronic cough, the Company has already filed a pre-IND application with the U.S. FDA and has announced that it has received positive feedback. The Company will take additional time to review the full data set before a decision is made to pursue an independent Phase 2b study of chronic cough or to focus on Ifenprodil as a potential new IPF drug that also reduces cough for those patients that are suffering from both. The invention claims treating interstitial lung disease, including IPF, with Ifenprodil. The base claims of the patent will be valid through 2040, excluding any patent term adjustments or extensions which may provide additional protection. The Company also has active patent applications for Ifenprodil for the same compositions and methods in the U.S., Europe, China and Japan.
