Previous Clinical Trial Results
Haduvio™ (oral nalbuphine ER) achieved statistically significant reductions in cough frequency in patients with either IPF or RCC.
%
of IPF Patients Experience Chronic Cough
Phase 2a Cough and NALbuphine (CANAL) Trial
(N=38)
Strong Efficacy
Data from the full set of (N=38) in the Phase 2 CANAL trial for adults with chronic cough in IPF showed a 52.5% change compared to placebo (p<0.0001), with a 75.1% reduction in the geometric mean percent change in daytime cough frequency for Haduvio.
Cough reduction over a 24-hour period was also measured, and the data also demonstrated a significant reduction in cough similar to the daytime measurement. Daytime Cough Endpoint calculated as geometric mean percent change.
Strong Efficacy
(N=38)
Data from the full set of (N=38) in the Phase 2 CANAL trial for adults with chronic cough in IPF showed a 52.5% change compared to placebo (p<0.0001), with a 75.1% reduction in the geometric mean percent change in daytime cough frequency for Haduvio.
Cough reduction over a 24-hour period was also measured, and the data also demonstrated a significant reduction in cough similar to the daytime measurement. Daytime Cough Endpoint calculated as geometric mean percent change.
Broad Coverage
The strength of the CANAL data was also analyzed by the percentage of responders that experienced a 30%, 50%, and 75% reduction in their 24-hour cough frequency from baseline. A 20-30% reduction in cough frequency is considered to be clinically meaningful and 97% of Haduvio patients saw at least a 30% reduction in 24-hour cough frequency. Responders endpoint calculated as geometric mean percent change in 24Hr cough frequency from study baseline
(Nal ER=29, PBO=37)
Broad Coverage
(Nal ER=29, PBO=37)
The strength of the CANAL data was also analyzed by the percentage of responders that experienced a 30%, 50%, and 75% reduction in their 24-hour cough frequency from baseline. A 20-30% reduction in cough frequency is considered to be clinically meaningful and 97% of Haduvio patients saw at least a 30% reduction in 24-hour cough frequency. Responders endpoint calculated as geometric mean percent change in 24Hr cough frequency from study baseline
(N=38)
Rapid Onset of Effect
Those on Haduvio reported a significant decrease in their cough as early as day 3 when compared to placebo via a patient reported outcome. EXACT2 endpoint calculated as mean change from baseline.
Rapid Onset of Effect
(N=38)
Those on Haduvio reported a significant decrease in their cough as early as day 3 when compared to placebo via a patient reported outcome. EXACT2 endpoint calculated as mean change from baseline.
Reducing Bouts
Cough bouts occur when consecutive coughs occur close to each other, which has dramatic impacts on patients, who try to catch their breath. These bouts happen when more than 2 coughs occur close together. Regardless of the time period used between coughs to define a bout, Haduvio significantly reduced cough bouts.
(N=38)
Reducing Bouts
(N=38)
Cough bouts occur when consecutive coughs occur close to each other, which has dramatic impacts on patients, who try to catch their breath. These bouts happen when more than 2 coughs occur close together. Regardless of the time period used between coughs to define a bout, Haduvio significantly reduced cough bouts.
Phase 2a Refractory Chronic Cough Improvement Via Nalbuphine ER (RIVER) Trial
In March 2025, we announced positive results from our Phase 2a RIVER trial in patients with RCC, including patients with unexplained chronic cough. The results from this trial supported Haduvio’s potential in treating chronic cough across indications through both the objective cough monitor and patient reported outcomes.
Statistically Significant Primary Endpoint
Haduvio met the primary endpoint with a statistically-significant reduction in 24-hour cough frequency with a 67% reduction from baseline (p<0.0001), and a 57% placebo-adjusted change.
Statistically Significant Primary Endpoint
Haduvio met the primary endpoint with a statistically-significant reduction in 24-hour cough frequency with a 67% reduction from baseline (p<0.0001), and a 57% placebo-adjusted change.
Rapid Reduction in Cough Frequency
Haduvio demonstrated a statistically significant reduction in 24-hour cough at Day 7 (27 mg BID), the earliest objective cough reading with the lowest assessed dose.
Rapid Reduction in Cough Frequency
Haduvio demonstrated a statistically significant reduction in 24-hour cough at Day 7 (27 mg BID), the earliest objective cough reading with the lowest assessed dose.
Broad Clinically Meaningful Effect
84% of those treated with Haduvio saw a clinically meaningful reduction in their 24-hour cough frequency compared to 29% of those treated with placebo. 77% of Haduvio treated patients achieved a 50% or greater reduction in their cough frequency compared with 15% on Placebo.
Broad Clinically Meaningful Effect
84% of those treated with Haduvio saw a clinically meaningful reduction in their 24-hour cough frequency compared to 29% of those treated with placebo. 77% of Haduvio treated patients achieved a 50% or greater reduction in their cough frequency compared with 15% on Placebo.
Consistency Across Baseline Cough Frequency
Haduvio demonstrated a statistically-significant reduction in 24-hour cough frequency with a placebo adjusted change of 51% in the severe cough (20+ coughs/hour) subgroup (p<0.0001) and 75% in the moderate cough (10-19 coughs/hour) subgroup (p<0.0001).
Safety
Over 1,000 patients have been dosed with Haduvio across various indications with some patients treated for up to 1-year.
The safety results of the CANAL and RIVER trials were generally consistent with the known safety profile of Haduvio from previous trials.
Adverse events most commonly observed during the CANAL trial were nausea, fatigue, constipation, dizziness, somnolence, vomiting, headache, anxiety and depression. These were generally mild to moderate and lasted 3-6 days.
Adverse events most commonly observed during the RIVER trial were constipation, nausea, somnolence, headache, dizziness, and fatigue and there were no treatment emergent serious adverse events.
Current Clinical Trials
Based on the strength and consistency of these results, we are running a Phase 2b trial in IPF patients with chronic cough and are planning a future RCC dose ranging study.