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1 Making Oraquick quicker Real world data on pan-genotypic regimens - PDF document

Feb 22, 2023 •308 likes •355 views

Disclosures Dr. Feld International Liver Congress Research : Abbott, Abbvie, Gilead, Janssen, Merck Consulting : Abbvie, Gilead, Merck 2019: Update from Vienna Dr Shah Jordan J. Feld MD MPH Consulting Fees: Abbvie, Gilead, Merck,

  1. Disclosures Dr. Feld International Liver Congress • Research : Abbott, Abbvie, Gilead, Janssen, Merck • Consulting : Abbvie, Gilead, Merck 2019: Update from Vienna Dr Shah Jordan J. Feld MD MPH • Consulting Fees: Abbvie, Gilead, Merck, Intercept, Lupin Toronto Centre for Liver Disease Sandra Rotman Centre for Global Health University of Toronto Learning Objectives Outline • HCV – Screening & linkage to care 1. Appreciate recent advances in HBV and HCV presented at the – Treatment efficacy International Liver Congress 2019 – Treatment monitoring – HCC post-SVR • HBV 2. Put into context the recent Phase 3 trial results for a new therapy – Current therapies for NASH • Cancer risk • Transmission risk • NASH – Obeticholic acid for NASH – REGENERATE Trial HCV Care Cascade: Diagnosis Gaps by Physician Type HCV Care Cascade: Treatment Gaps by Physician Type HCV Diagnosis HCV Treatment HCV Detection HCV Confirmation by Specialty (%) by Specialty (%) by Specialty (%) by Specialty (%) 95% Generalist* Generalist* Gap: patients with ≥ 2 HCV HCV specialist † HCV specialist † Gap: Ab+ patients seen by RNA tests by physician OB/GYN 46 physician group who did not OB/GYN group but did not receive Other have confirmatory HCV RNA % Other treatment from that Missing specialty 83% testing by that physician Missing specialty physician group group *Includes primary *Includes primary 90% of diagnosed care, family practice, 46% of Ab+ care, family practice, 87% 49 patients received internal medicine. internal medicine. patients received † Includes no HCV therapy % † Includes no hepatologist, hepatologist, gastroenterologist, HCV RNA test gastroenterologist, and ID specialist. 91% and ID specialist. 57 % 91% 54 % Rege. EASL 2019. Abstr PS-066. Rege. EASL 2019. Abstr PS-066. 1

  2. Making Oraquick quicker Real world data on pan-genotypic regimens 20 Mean OraQuick Viremic Non- Predictive Time (minutes) HCV Ab Viremic Values p < 0.001 15 PPV: 86.7% Positive at 5 102 16 95% CI (0.79- 10 min 0.92) NPV: 100.0% 5 Negative at 5 0 15 98% CI (0.73- min 1.00) 0 Sensitivity: 100.0% Specificity: 48.3% Viremic Non-Viremic 98% CI (0.96-1.00) 95% CI (0.32-0.65) If negative at 5 minutes, can tell people they are not viremic Not surprising but very reassuring data – this should apply to most of our patients Once positive, stays positive – no reason to wait to 20’ Smookler, Vanderhoff EASL 2019 Mangia ILC 2019 GS-03, Cornberg M ILC 2019 GS-07 SMART-C: Monitoring During GLE/PIB in SMART-C: Efficacy and Safety Treatment-Naive Patients With GT1-6 HCV Infection  Multicenter, randomized, open-label Difference: -3.2% Treatment-Emergent Standard Simplified (95% CI: -8.2 to 1.8) phase IIIb study Wk 8 AEs, n (%) (n = 127) (n = 253) 98 97 98 97 95 100 92 AEs 70 (55) 133 (53) Standard GLE/PIB With Simplified Monitoring Treatment-naive patients with  Grade 1/2 80 69 (54) 131 (52) (n = 253) Simplified GT1-6 HCV infection, HCV RNA SVR12 (%)  Grade 3 1 (0.8) 2 (0.8) > 10,000 IU/mL, and no GLE/PIB With Standard Monitoring  Grade 4 60 0 0 cirrhosis* (n = 127) (N = 380)  Common AEs (> 5%) Overall performed very well but did not quite reach noninferiority 40 AEs and adherence assessed by study nurse via phone contact at Wks 4 and 8 in all patients. GLE/PIB dosed orally at 300/120 mg  Fatigue 30 (14) 52 (15)  QD. Highlights need for good patient selection for this approach  Headache 26 (12) 43 (13) 20 *Exclusion criteria: anticipated poor adherence, IDU within past 6 mos, positive urine drug screen. 121/ 233/ 121/ 233/ 121/ 233/  Nausea 25 (12) 17 (5) n/N =   Primary endpoint: SVR12 in ITT population 127 253 123 241 123 239 Simplified monitoring: Medication dispensed 0 Serious AEs 0 3 (1.2) PP † (6% noninferiority margin) ITT mITT* at BL; no on-treatment clinic visits Unscheduled visits *Excludes death (n = 1), LTFU (n = 14), or missing HCV RNA (n = 1).   Secondary endpoints: SVR12 in mITT and PP † Excludes discontinuation (n = 2) in addition to mITT exclusions.  On treatment Standard monitoring: Medication dispensed 3 (2) 11 (4) populations, adherence by Wk 20 pill count,   Total 8 (6) 20 (8) at BL and Wk 4; clinic visits with physician, VF: 2 (1.6%) standard vs 6 (2.4%) simplified treatment discontinuation and completion, study nurse, and pathology at Wks 4 and 8  Adherence > 95%: 98% standard vs 96% simplified safety Dore, LB – PS 178 EASL 2019 Dore, LB – PS 178 EASL 2019 Factors associated with HCC risk Risk of HCC after SVR Factors associated with HCC after SVR in patients with F3/F4 Lau EASL 2019 2

  3. Change with treatment does not help Effective for finding low risk patients If validated, could forego surveillance in low risk group Lau EASL 2019 Lau EASL 2019 Therapy for HBV – is 1 nuc better than another? Does U=U for HBV? • Usually we think of Nucs (tenofovir or entecavir) as almost interchangeable Serum from patients with HBV on nuc therapy with HBV DNA detectable but <LLOQ used to infect • Slight differences in resistance profile (less with tenofovir) and renal toxicity (less with entecavir) humanized mice • Recent study from Korea found a higher of liver cancer in those treated with entecavir vs tenofovir Study from Hong Kong – consecutive treated HBV 2008-2018 28,041 ETV with 1,386 HCC vs 1,309 with TDF with 8 HCCs • 9 of 31 established viremia • Unclear if they had taken <LLOD • But highlights transmission of HBV • Importance of vaccination • Importance of disclosure Lower risk of cancer with tenofovir treatment Burdette ILC 2019 PS 150 T CK Yip, G Wong EASL 2019 REGENERATE: Study Design REGENERATE Primary Endpoint: Fibrosis Improvement  Study met fibrosis primary endpoint at 18 mos (ITT)  International, randomized, double-blind phase III study of FXR agonist obeticholic acid End of Study  In PP analysis, OCA 25 mg QD Fibrosis Improvement Stratified by T2DM, treatment with Mo 18 End of Study (Event Driven) thiazolidinediones or vitamin E Interim Analysis (Histology) (Event Driven) by ≥ 1 Stage With No NASH Worsening also associated with fibrosis 100 improvement across subgroups OCA 10 mg QD 80 defined by fibrosis stage, NAS, (n = 312) Patients with biopsy-confirmed Patients (%) T2DM status P = .0002 60 NASH, fibrosis stage 2/3, OCA 25 mg QD NAFLD activity score ≥ 4 P = .04 (n = 308) (target N ~ 2400) 40 Placebo QD 23.1 17.6 20 (n = 311) 11.9  Primary endpoint at interim analysis by paired biopsy: either fibrosis improvement by n = 311 312 308  Primary endpoint at interim analysis by paired biopsy: either fibrosis improvement by 0 ≥ 1 stage without NASH worsening or NASH resolution without fibrosis worsening Placebo OCA 10 mg QD OCA 25 mg QD ≥ 1 stage without NASH worsening or NASH resolution without fibrosis worsening Younossi. EASL 2019. Abstr GS-06. Slide credit: clinicaloptions.com Younossi. EASL 2019. Abstr GS-06. Younossi. EASL 2019. Abstr GS-06. Slide credit: clinicaloptions.com 3

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