Slide 1: Nalbuphine Tablets for Cough in Patients with Idiopathic Pulmonary Fibrosis
W Published May 22, 2023 EJM Evidence DOI: 10.1056/EVID0a2300083 Nalbuphine Tablets for Cough in Patients with Idiopathic Pulmonary Fibrosis Toby M. Maher, M.D., Ph.D.,1 Cristina Avram, M.D.,> Enoch Bortey, Ph.D.,4 Simon P. Hart, M.D., Ph.D.,° Nikhil Hirani, M.D., Ph.D.,° Philip L. Molyneux, M.D., P
Slide 2: Efficacy of Oral Nalbuphine Extended Release in Patients With IPF Related Chronic Cough: a Phase 2 Study
Efficacy of Oral Nalbuphine Extended Release in Patients With Idiopathic Pulmonary Fibrosis Related Chronic Cough: a Phase 2 Study Toby M. Maher1; Cristina Avram2; Enoch Bortey3; Simon P. Hart4; Nikhil Hirani5; Philip L. Molyneaux6; Joanna C. Porter7; Thomas Sciascia 3 1Keck School of Medicine, Univ
Slide 3: Disclosure to Learners
Disclosure to Learners Financial Relationships with “ineligible companies” within the past 24 months: AstraZeneca, grants/funding GlaxoSmithKline R&D, grants/funding Consultant: AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol Myer Squibb, Fibrogen, Galapagos, Galecto, GlaxoSmit
Slide 4: Background
Background • Cough is a major cause of morbidity in patients with idiopathic pulmonary fibrosis (IPF)1, which lacks effective therapies2 • Dual-acting opioid agonists/antagonists are hypothesised to reduce chronic cough via the opioid receptors mechanism • May influence both the central and of actio
Slide 5: Study design
Study design Treatment Treatment Period 1 Period 2 • Randomised, double-blind, placebo-controlled, crossover trial Randomization nalbuphine ER BID Placebo (Day 1 – Day 22) 2-week washout (Day 1 – Day 22) with two 22-day treatment period / treatment 2-week follow-up periods separated by a 2-week Plac
Slide 6: Endpoints
Endpoints PRIMARY ENDPOINT • Geometric mean percent change in daytime cough frequency from baseline as measured by a digital cough monitor (VitaloJAK®) between the nalbuphine ER and placebo treatments at Day 22 SECONDARY ENDPOINTS • 24-hour cough frequency at Day 22 • Evaluating Respiratory Symptoms
Slide 7: Patient disposition – completer analysis set
Patient disposition – completer analysis set Screened N = 56 • Of the 56 screened patients, 38 (14) Screen failure (25%) comprised the 1-period full analysis set Randomised/Enrolled N = 42 • The completers set was (1) Protocol deviation (2.4%) (1) Withdrawal by subject (2.4%) comprised of the 28 pat
Slide 8: Baseline Characteristics
Baseline Characteristics Completer Analysis Set* (N = 28) • Patients were primarily male with Male, n (%) 23 (82.1) a mean age of > 70 years and a Age (years), mean 74 baseline mean daytime cough Anti-fibrotic usage, n (%) 15 (53.6) frequency of 28 coughs per hour Daytime cough frequency (coughs/hou
Slide 9: Primary Endpoint Achieved Statistically Significant Reduction in Daytime Cough Frequency
Primary Endpoint Achieved Statistically Significant Reduction in Daytime Cough Frequency Geometric mean change from study baseline in daytime coughs per hour (N = 28) • 76.2% reduction in daytime cough 0% frequency at Day 22 with nalbuphine ER Percent change in coughs/hour -10% (nalbuphine ER, n = 2
Slide 10: Reduction of Cough Frequency and Placebo-Adjusted Change Were Consistent Between Daytime and 24-Hour
Reduction of Cough Frequency and Placebo-Adjusted Change Were Consistent Between Daytime and 24-Hour Cough Frequency Geometric mean percent change from study baseline in coughs per hour completers analysis set (N = 28) Daytime 24 hr 0% from study baseline Percent change in -20% -31.4% -33.2% coughs/
Slide 11: Magnitude of Efficacy was Consistent Independent of Background Anti-Fibrotic Therapy
Magnitude of Efficacy was Consistent Independent of Background Anti-Fibrotic Therapy • Cough reduction was seen in patients both with and without concomitant anti-fibrotic medication at Day 22
Slide 12: Post-Hoc Responder Analysis Shows Clear Separation Between Nalbuphine ER vs Placebo
Post-Hoc Responder Analysis Shows Clear Separation Between Nalbuphine ER vs Placebo at All Thresholds (N = 28) ** • 96% of nalbuphine ER 96% 100% patients saw a reduction in ** 80% 76% 24-hour cough frequency at Day 22 (97% in full analysis 60% set) * 43% 40% 32% 26% • 75% of nalbuphine ER 20% patie
Slide 13: Safety
Safety • No deaths reported • 2 reported serious adverse events (lung infection, urosepsis) were not considered treatment-related • The adverse event profile of the drug in the IPF population is consistent with the safety profile noted in all other past studies in which nalbuphine ER was investigate
Slide 14: Conclusions
Conclusions • Nalbuphine ER demonstrated a significant reduction in chronic cough associated with IPF in the phase 2 completers analysis set (N = 28) • 46% placebo-adjusted reduction in the geometric mean percent change from study baseline for nalbuphine ER in daytime cough frequency to Day 22 of tr