RedHill Biopharma Ltd. · NASDAQ:RDHL
RedHill Biopharma — Innovations in Gastroenterology 2017 Symposium
21 slides from RedHill Biopharma's conference presentation, Jan 4, 2017
Slide 1: Phase III Study of Rifabutin Triple Therapy (RHB-105) for H. pylori Infection
A Randomized Double Blind Placebo Controlled Phase III Study to Assess the Safety and Efficacy of Rifabutin Triple Therapy (RHB-105) for Helicobacter pylori (H. pylori) Infection in Dyspepsia Patients I. Kalfus MD, D. Riff MD, R. Fathi PhD, D. Graham MD
Slide 2: Financial and Other Disclosures
Financial and Other Disclosures • Data from IRB-approved human research is presented I have the following financial interests or Disclosure code relationships to disclose: Consultant, Medical RedHill Biopharma Ltd. Director and Shareholder 2
Slide 3: Indication
Indication • H. pylori is an infectious disease¹ (Kyoto) – Irrespective symptoms and stage of disease • A test-and-treat strategy is appropriate for uninvestigated dyspepsia² (Maastricht V) • H. pylori infected individuals should be offered eradication therapy with caveats – Age, alarm symptoms and
Slide 4: H. pylori – A Global Issue
H. pylori – A Global Issue • ~50% of world’s population is infected – 30-40% in US with 60-70% sub-populations¹ – 60% in Israel² • First course of tx offers – Greatest chance at eradication – Reduced risk of gastritis, PUD and gastric cancer³ • Treatment failure associated with increased risk of ant
Slide 5: The Problem
The Problem • Up to 30% failure to eradicate with standard triple therapy • ↑resistance to clarithromycin & metronidazole 5
Slide 6: The Solution
The Solution • RHB-105 – “All-in one” capsule formulation – 4 capsules tid • Amoxicillin 1000 mg tid → 3 gm daily • Rifabutin 50 mg tid → 150 mg daily • Omeprazole 40 mg tid → 120 mg daily – >90% efficacy in AMX/RIF/PPI single site SOC failed tx study¹ – Minimal resistance noted to AMX/RIF ¹Borody e
Slide 7: Randomized DBPC Phase III Study (ERADICATE Hp)
Randomized DBPC Phase III Study (ERADICATE Hp) • Assess the Safety and Efficacy of RHB-105 in the Treatment of Confirmed Helicobacter pylori Infection in Dyspepsia Patients – Negative ¹³C UBT 28-35 days post tx • 118 Subjects • 2:1 Randomization – RHB-105:Placebo – 77:41 – 63% Female:37% Male – 92%
Slide 8: Major Inclusion/Exclusion Criteria
Major Inclusion/Exclusion Criteria • Inclusion Criteria ―Aged 18 – 65 years ―Positive for H. pylori by 13C UBT and fecal antigen test or gastric biopsy within 6 weeks ―Dyspeptic symptoms for at least 2 weeks – recurrent pain/discomfort in upper abdomen • Exclusion Criteria ―Alarm symptoms/signs ―Ant
Slide 9: Assumptions and Endpoints
Assumptions and Endpoints • RHB-105 at least 20% more effective than 70% historical control • 90% power, 0.025 one sided • Primary endpoint – mITT population – RHB-105 success rate vs 70% reported effectiveness of SOC triple therapy – Comparison vs placebo would not be informative • Secondary endpoi
Slide 10: Protocol Defined Populations
Protocol Defined Populations • Intent-to-Treat (ITT), n=77 – At least one dose of RHB-105 drug • Modified Intent-to-Treat (mITT), n=66 – At least one dose of RHB-105 and ¹³C UBT day 28-35 • 5 subjects withdrawn due to poor compliance (<75%) • 5 subjects lost to follow up • 1 subject with AE of nause
Slide 11: Disposition of All Subjects
Disposition of All Subjects RHB-105 Placebo Total N = 77 N = 41 (N = 118) Completed main study 63 (81.8%) 30 (73.2%) 93 (78.8%) Discontinued from main study 14 (18.2%) 11 (26.8%) 25 (21.2%) Reason for early termination: Lost to follow-up 6 (7.8%) 7 (17.1%) 13 (11.0%) <75% compliance with drug 5 (6.5
Slide 12: Efficacy Results
Efficacy Results • Primary endpoint – mITT RHB -105 success rate 89.4% (59/66 subjects), p-value<0.001 • Sensitivity Analyses – PP success rate 88.9% (56/63), p-value<0.001 – ITT success rate 76.6% (59/77), p-value=0.085 – SOC eradication rate of 63% (17/27 subjects) 12
Slide 13: SOC Success Rate Post Tx
SOC Success Rate Post Tx H. pylori Eradication Treatment Success Failure P-value by Group Population RHB-105 59 (89.4%) 7 (10.6%) mITT SOC tx naive 17 (63.0%) 10 (37.0%) 0.006 ITT RHB-105 59 (76.6%) 18(23.3%) 0.009 SOC tx naive 17 (52.0%) 16 (50.0%) 13
Slide 14: Placebo Comparator Not Informative
Placebo Comparator Not Informative mITT RHB-105 Placebo Total N = 66 N = 37 Success 59 (89.4%) 1 (2.7%) 60 Failure 7 (10.6%) 36 (97.3%) 43 P-value < 0.001 PP N = 63 N = 36 Success 56 (88.9%) 1 (2.8%) 57 Failure 7 (11.1%) 35 (97.2%) 42 P-value < 0.001 ITT N = 77 N = 41 Success 59 (76.6%) 1 (2.4%) 60
Slide 15: Safety
Safety • 151 AEs in 55 of 118 subjects – 103 AEs in RHB-105 arm:48 AEs in placebo arm • 55 TEAEs – 31 mild – 20 moderate – 4 severe • RHB-105: Rash / diarrhea • Placebo: Anemia / perirectal abscess • 1 Additional anemia noted at baseline in RHB-105 subject 15
Slide 16: Summary of Treatment-Emergent Adverse Events (>5% Safety Population)
Summary of Treatment-Emergent Adverse Events (>5% Safety Population) RHB-105 Placebo Total N = 77 N = 41 N = 118 Category # Pts (%) # AEs # Pts (%) #AEs # Pts (%) # AEs All System 38 (49.4%) 103 17 (41.5%) 48 55 (46.6%) 151 Organ Classes Diarrhea 11 (14.3%) 14 4 (9.8%) 4 15 (12.7%) 18 Abdominal 5 (6
Slide 17: Summary of Treatment-Related TEAEs (>5% Safety Population)
Summary of Treatment-Related TEAEs (>5% Safety Population) RHB-105 Placebo Total N = 77 N = 41 N = 118 Category #Pts (%) # AEs #Pts (%) #AEs #Pts (%) # AEs All System 38 (49.4%) 103 17 (41.5%) 48 55 (46.6%) 151 Organ Classes Related 23 (29.9%) 40 8 (19.5%) 23 31 (26.3%) 63 Not Related 15 (19.5%) 63
Slide 18: Safety
Safety • 2 SAEs unrelated to study drug – Anemia noted at screening – subject completed study (RHB-105 arm) – Perirectal abscess 18 days after completing study drug (placebo arm) • 2 Early discontinuations in RHB-105 Arm – Pharyngitis with poor compliance – Nausea with poor compliance 18
Slide 19: RHB-105 Study Conclusions
RHB-105 Study Conclusions • A novel “3 in 1” potential new therapy • Safe, well tolerated and more effective than historical or physician selected SOC treatment • Confirmatory Phase III study planned • Subject compliance and retention essential 19
Slide 20: Thank You
Thank You • Subjects and Study Site personnel who participated and supported this study • David Graham and other PIs • Special thanks to Dennis Riff, lead enroller 20
Slide 21: Thank You
Rede niiia, Biopharma HELICOBACTER PYLORI INFECTION COMMON PRECURSOR RISK FACTOR FOR OF GASTRITIS AND GASTRIC CARCINOMA PEPTIC ULCERS KS OG TREATMENT: RHB-105 AMMONIA ALSO - NEUTRALIZES ACID PH, er» WHICH ALLOWS THE ORGANISM ~ TO LIVE IN THE STOMACH
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