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Poster Session A - Sunday Afternoon

A0089 - Naloxegol Provides Clinically Meaningful Healthcare-Related Quality of Life (HR-QoL) Improvement (PAC-QOL) in Patients With Opioid-Induced Constipation (OIC): A Pooled Analysis of Two Global Phase 3 Studies of Naloxegol

Sunday, October 23, 2022

5:00 PM – 7:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Darren M. Brenner, MD, FACG

Northwestern University Feinberg School of Medicine
Chicago, IL

Darren M. Brenner, MD, FACG¹, Carol Rockett, PharmD², Mansi Jamindar, PharmD³, Enoch Bortey, ⁴, June Almenoff, MD, PhD², Brooks D. Cash, MD, FACG⁵
¹Northwestern University Feinberg School of Medicine, Chicago, IL; ²RedHill Biopharma, Raleigh, NC; ³RedHill Biopharma Inc, Holly Springs, NC; ⁴Pharmaceutical Development Strategies LLC, Chapel Hill, NC; ⁵University of Texas Health Science Center, Houston, TX

Introduction: OIC negatively impacts patients’ HR-QOL. Naloxegol (Movantik®), a peripherally acting mu-opioid receptor antagonist (PAMORA) proved effective in treating OIC symptoms in adults with chronic non-cancer pain in two pivotal phase 3 trials (KODIAC 4/5; NCT01309841/NCT01323790). This pooled analysis evaluated HR-QOL improvement utilizing the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL) in these two randomized, placebo-controlled trials.

Methods: PAC-QOL scores were collected during KODIAC 4/5 as supportive efficacy measures. Scoring ranged from 0 (absence of symptoms) to 4 (very severe) for each domain (Physical Discomfort, Psychosocial Discomfort, Worries/Concerns, and Satisfaction). Minimal clinically important difference (MCID) thresholds of 0.5 based on literature and naloxegol real world studies, and 0.8 based on anchor method assessment were evaluated in the pooled KODIAC 4/5 data and used to identify responders and non-responders.

Results: 1337 patients (naloxegol (25mg, 12.5mg) or placebo (PBO)) were assessed in this analysis. The overall baseline values for PAC-QOL Total, Physical discomfort, Psychosocial Discomfort, Worries/Concerns, and Satisfaction scores were 2.0, 2.1, 1.3, 2.0, and 3.3, respectively.

For MCID >0.5, a higher proportion of PAC-QOL responders were observed for naloxegol (25 mg: 66.07%; 12.5mg: 68.47%) vs PBO (58.95%) at Wk 12. Odds ratios (OR) were 1.4 (p=0.047) for 25mg and 1.5 (p=0.017) for 12.5mg vs. PBO, indicating significance with 40-50% higher likelihoods of clinically meaningful HR-QOL improvement than PBO.

For MCID >0.8, higher proportions of PAC-QOL responders were also observed for naloxegol (25mg: 52.68%; 12.5mg: 56.25%) vs. PBO (45.73%). ORs were 1.4 (p=0.068) for 25mg and 1.5 (p=0.010) for 12.5mg vs. PBO.

ORs were generally consistent between MCID >0.8 and 0.5 (Table 1).

Significantly greater proportions of responders achieved Satisfaction for 25mg and 12.5mg vs. PBO (p< 0.05) for both MCID thresholds. Other subdomains also showed statistically significant and numerical improvements with naloxegol (25mg, 12.5 mg) vs. PBO. (Figures 1a-d).

Discussion: In two phase 3 pivotal clinical trials, patients with OIC achieved clinically relevant HR-QOL improvements and reported significant satisfaction with naloxegol at both MCID thresholds.

Figure: Figure 1a-d. Likelihood of Achieving PAC-QOL MCID at Week 12: Naloxegol vs. Placebo (KODIAC 4/5; ITT Population)

Placebo

(N=363)^a

n (%)

Naloxegol 12.5 mg

(N=352)^a

n (%)

Naloxegol 25 mg

(N=336)^a

n (%)

Naloxegol 12.5 mg vs. Placebo

(95% CI)

p-value

Naloxegol 25 mg vs. Placebo

(95% CI)

p-value

Proportion of PAC-QOL Responders Achieving MCID > 0.5

214 (58.95%)

241 (68.47%)

222 (66.07%)

1.500

(1.077, 2.089)

0.0165

1.395

(1.004, 1.938)

0.0471

Proportion of PAC-QOL Responders Achieving MCID > 0.8

166 (45.73%)

198 (56.25%)`

177 (52.68%)

1.517

(1.103, 2.087)

0.0104

1.348

(0.978, 1.858)

0.0682

^aNumber of analyzable subjects with complete PAC-QOL data for 12-wks

PAC-QOL, Patient Assessment of Constipation Quality of Life questionnaire

MCID, minimal clinically important difference

OR, odds ratio

CI, confidence interval

Table: Table 1. PAC-QOL Total Score: Proportion of Responders Achieving MCID at Week 12 (KODIAC 4/5; ITT Population)

Disclosures:

Darren Brenner: Abbvie – Advisory Committee/Board Member, Consultant, Speakers Bureau. Alnylam – Advisory Committee/Board Member, Consultant. AlphaSigma – Advisory Committee/Board Member, Consultant. Ardelyx – Advisory Committee/Board Member, Consultant, Speakers Bureau. Arena – Advisory Committee/Board Member, Consultant. Bayer – Consultant. Gemelli – Advisory Committee/Board Member. International Foundation for GI Disorders (IFFGD) – Board of Directors. Ironwood – Advisory Committee/Board Member, Consultant, Speakers Bureau. Qol Medical – Advisory Committee/Board Member. Redhill – Advisory Committee/Board Member, Consultant, Speakers Bureau. Salix – Advisory Committee/Board Member, Consultant, Speakers Bureau. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Vibrant – Advisory Committee/Board Member, Consultant.

Carol Rockett: RedHill Biopharma – Employee.

Mansi Jamindar: RedHill Biopharma – Employee.

Enoch Bortey: RedHill Biopharma – Consultant.

June Almenoff: RedHill Biopharma – Employee.

Brooks Cash: AbbVie – Consultant, Speakers Bureau. Ardelyx – Consultant, Speakers Bureau. RedHill – Consultant. Salix Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speakers Bureau.

Darren M. Brenner, MD, FACG¹, Carol Rockett, PharmD², Mansi Jamindar, PharmD³, Enoch Bortey, ⁴, June Almenoff, MD, PhD², Brooks D. Cash, MD, FACG⁵. A0089 - Naloxegol Provides Clinically Meaningful Healthcare-Related Quality of Life (HR-QoL) Improvement (PAC-QOL) in Patients With Opioid-Induced Constipation (OIC): A Pooled Analysis of Two Global Phase 3 Studies of Naloxegol, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.