Phathom Pharmaceuticals, Inc. · NASDAQ:PHAT
Phathom Pharmaceuticals — Technical Presentation (May 2024)
23 slides from Phathom Pharmaceuticals's technical presentation, May 2024
Slide 1: Vonoprazan for the Treatment of Heartburn in Non-Erosive Reflux Disease: A Randomized Trial
VONOPRAZAN FOR THE TREATMENT OF HEARTBURN IN NON-EROSIVE REFLUX DISEASE: A RANDOMIZED TRIAL Loren Laine1, Stuart Spechler2, Rena Yadlapati3, Felice Schnoll-Sussman4, Neila Smith5, Eckhard Leifke5, Tom Harris5, Barbara Hunt5, Ronnie Fass6, Philip Katz4 1Yale School of Medicine, New Haven, CT and VA C
Slide 2: Introduction
INTRODUCTION GERD is a common GI disorder: U.S. pooled prevalence 21% • Most patients do not have endoscopic evidence of erosive esophagitis • GERD-like symptoms (heartburn, regurgitation) without erosive esophagitis: diagnosed as non-erosive reflux disease (NERD) PPIs most commonly prescribed medic
Slide 3: Introduction
INTRODUCTION Potassium-competitive acid blockers (PCABs) provide more potent and prolonged inhibition of gastric acid than PPIs Small observational study reported 18 (69%) of 26 patients with PPI-resistant NERD had symptom improvement when changing to vonoprazan Two Japanese RCTs in NERD failed to s
Slide 4: Introduction
INTRODUCTION We performed a double-blind randomized trial of U.S. patients diagnosed with NERD to assess heartburn control with vonoprazan vs. placebo over 4 weeks followed by a 20-week active treatment extension period to assess longer-term treatment effect of vonoprazan
Slide 5: Methods: Subjects
METHODS Subjects • Adults diagnosed with symptomatic GERD • Heartburn predominant symptom, onset ≥ 6 months prior to screening • No erosive esophagitis or Barrett’s on screening endoscopy • H. pylori negative (tested during screening) • Subjects received rescue antacid to use as needed for heartburn
Slide 6: Methods: Study Flow
METHODS Study Flow Screening Placebo-Controlled Period Extension Period 4-week F/U (≤5 Weeks) (4 Weeks) (20 Weeks) period Vonoprazan Placebo Re- 10 mg QD randomize QD 1:1 Vonoprazan Heartburn ≥4 20 mg QD days in any After end consecutive of active 7-day period Vonoprazan Vonoprazan treatment 10 mg Q
Slide 7: Methods: Efficacy Endpoints, Placebo-Controlled Period
METHODS Efficacy Endpoints: Placebo-Controlled Period • Primary • Percentage of 24-hour heartburn-free days • Morning and evening diary entries: no heartburn and no rescue antacid use • Secondary • Percentage of days without rescue antacid use • Exploratory • Percentage of days without daytime heart
Slide 8: Methods: Efficacy Endpoints, Extension Period
METHODS Efficacy Endpoints: Extension Period Exploratory • Percentage of 24-hour heartburn-free days • Percentage of days without rescue antacid use • Percentage of days without daytime heartburn • Percentage of days without nighttime heartburn • Mean severity of heartburn
Slide 9: Primary and Secondary Endpoints Assessed Using a Fixed-Sequence Testing Procedure
PRIMARY AND SECONDARY ENDPOINTS ASSESSED USING A FIXED-SEQUENCE TESTING PROCEDURE Population: All Randomized Subjects Who Received ≥1 Dose of Study Drug Vonoprazan 20 mg vs. placebo for percentage of 24-hour heartburn-free days Vonoprazan 10 mg vs. placebo for percentage of 24-hour heartburn-free da
Slide 10: Selected Baseline Characteristics: Placebo-Controlled Period
SELECTED BASELINE CHARACTERISTICS: PLACEBO-CONTROLLED PERIOD Placebo (N=258) Vonoprazan 10mg (N=257) Vonoprazan 20mg (N=257) Age, mean yrs 51.5 51.0 50.4 Female sex 179 (69.4%) 182 (70.8%) 166 (64.6%) Race White 205 (79.5%) 186 (72.4%) 185 (72.0%) Black 33 (12.8%) 38 (14.8%) 52 (20.2%) Asian 12 (4.7
Slide 11: Primary and Secondary Endpoints Assessed Using a Fixed-Sequence Testing Procedure
PRIMARY AND SECONDARY ENDPOINTS ASSESSED USING A FIXED-SEQUENCE TESTING PROCEDURE Vonoprazan 20 mg vs. placebo for percentage of 24-hour heartburn-free days LS means: 44.4% vs. 27.7%, Difference = 16.7%, p<0.0001 Vonoprazan 10 mg vs. placebo for percentage of 24-hour heartburn-free days LS means: 44
Slide 12: Percentage of Subjects Without Heartburn on Each Day of the Last Week of Screening and Placebo Period
PERCENTAGE OF SUBJECTS WITHOUT HEARTBURN ON EACH DAY OF THE LAST WEEK OF THE SCREENING PERIOD AND THE PLACEBO-CONTROLLED PERIOD
Slide 13: Percentage of Subjects Without Heartburn on Each Day: Day 1
PERCENTAGE OF SUBJECTS WITHOUT HEARTBURN ON EACH DAY OF THE LAST WEEK OF THE SCREENING PERIOD AND THE PLACEBO-CONTROLLED PERIOD Difference vs. Placebo: Day 1 Vonoprazan 20mg: 11.6% Vonoprazan 10mg: 8.3%
Slide 14: Percentage of Subjects Without Heartburn on Each Day: Day 2
PERCENTAGE OF SUBJECTS WITHOUT HEARTBURN ON EACH DAY OF THE LAST WEEK OF THE SCREENING PERIOD AND THE PLACEBO-CONTROLLED PERIOD Difference vs. Placebo: Day 2 Vonoprazan 20mg: 23.2% Vonoprazan 10mg: 18.1%
Slide 15: Results: Placebo-Controlled Period
RESULTS: PLACEBO-CONTROLLED PERIOD LS Mean LS Mean Difference Difference Vonoprazan 10mg Vonoprazan 20mg Placebo (N=258) Vonoprazan Vonoprazan (N=257) (N=257) 10mg vs. 20mg vs. Placebo Placebo LS Mean Median LS Mean Median LS Mean Median 24-hr heartburn- 27.7% 16.7% 44.8% 48.1% 44.4% 46.4% 17.1%* 16
Slide 16: Results: Placebo-Controlled Period
RESULTS: PLACEBO-CONTROLLED PERIOD LS Mean LS Mean Difference Difference Vonoprazan 10mg Vonoprazan 20mg Placebo (N=258) Vonoprazan Vonoprazan (N=257) (N=257) 10mg vs. 20mg vs. Placebo Placebo LS Mean Median LS Mean Median LS Mean Median 24-hr heartburn- 27.7% 16.7% 44.8% 48.1% 44.4% 46.4% 17.1%* 16
Slide 17: Results: Placebo-Controlled Period
RESULTS: PLACEBO-CONTROLLED PERIOD LS Mean LS Mean Difference Difference Vonoprazan 10mg Vonoprazan 20mg Placebo (N=258) Vonoprazan Vonoprazan (N=257) (N=257) 10mg vs. 20mg vs. Placebo Placebo LS Mean Median LS Mean Median LS Mean Median 24-hr heartburn- 27.7% 16.7% 44.8% 48.1% 44.4% 46.4% 17.1%* 16
Slide 18: Percentage of Subjects Without Heartburn: Placebo-Controlled and Extension Periods
PERCENTAGE OF SUBJECTS WITHOUT HEARTBURN ON EACH DAY OF THE PLACEBO-CONTROLLED PERIOD AND EXTENSION PERIOD
Slide 19: Results: Extension Period
RESULTS: EXTENSION PERIOD Placebo to Placebo to Vonoprazan Vonoprazan Vonoprazan 10mg Vonoprazan 20mg 10mg to 10mg 20mg to 20mg (N=119) (N=122) (N=247) (N=235) Mean Median Mean Median Mean Median Mean Median 24-hr heartburn- 61.9% 78.3% 62.9% 76.2% 62.6% 77.7% 60.7% 79.4% free days 24-hr days withou
Slide 20: Results: Extension Period
RESULTS: EXTENSION PERIOD Placebo to Placebo to Vonoprazan Vonoprazan Vonoprazan 10mg Vonoprazan 20mg 10mg to 10mg 20mg to 20mg (N=119) (N=122) (N=247) (N=235) Mean Median Mean Median Mean Median Mean Median 24-hr heartburn- 61.9% 78.3% 62.9% 76.2% 62.6% 77.7% 60.7% 79.4% free days 24-hr days withou
Slide 21: Mean Serum Gastrin Levels Throughout Study
MEAN SERUM GASTRIN LEVELS THROUGHOUT STUDY Placebo to Placebo to Vonoprazan Vonoprazan Vonoprazan 10mg Vonoprazan 20mg 10mg to 10mg 20mg to 20mg Baseline, placebo- 43.9 58.9 50.4 43.7 controlled period (N=114) (N=113) (N=230) (N=219) Baseline, 36.1 61.8 156.8 211.5 extension period (N=118) (N=120) (
Slide 22: Conclusions: Strengths and Limitations
CONCLUSIONS • Strengths • Double-blind, randomized design • 20-week active treatment extension for all subjects enrolled • Scant evidence from prior prospective trials of antisecretory therapy in NERD over longer periods and only in selected patients with symptomatic relief prior to entry • Generali
Slide 23: Conclusions
CONCLUSIONS The PCAB vonoprazan was efficacious in reducing heartburn symptoms in patients diagnosed with NERD • Benefit appeared to begin as early as the first day of therapy • Treatment effect persisted after the initial 4-week placebo- controlled period throughout the 20-week extension period • T
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