P0741 - Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) in Virally Suppressed Chronic Hepatitis B (CHB) Patients With Renal Impairment: Week 48 Results From a Phase 2 Open-Label Study

Sunday, October 24, 2021

3:30 PM – 7:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Award: Presidential Poster Award

Presenting Author(s)

Jake Winans, MSN, RN, FNP-C

Gilead Sciences
Gilbert, AZ, United States

Award: Presidential Poster Award

Harry Janssen, MD, PhD¹, Jeong Heo, MD, PhD², Claire Fournier, MD, PhD³, Sang Hoon Ahn, MD, PhD⁴, Carla S. Coffin, MD, MSc, FRCPC⁵, Yi-Hsiang Huang, MD, PhD⁶, Aric Josun Hui, MBCHB⁷, Magdy Elkhashab, MD, MSc, FRCPC⁸, Syed-Mohammed Jafri, MD⁹, Shuyuan Mo, PhD¹⁰, Jake Winans, MSN, RN, FNP-C¹¹, John Flaherty, PharmD¹⁰, Anuj Gaggar, MD¹², Wan-Long Chuang, MD¹³, Ed J. Gane, MBChB, MD¹⁴, Young-Suk Lim, MD, PhD¹⁵
¹University Health Network, Toronto, ON, Canada; ²Pusan National University Hospital, Busan, Pusan-jikhalsi, Republic of Korea; ³CHU Montreal, Montreal, PQ, Canada; ⁴Yonsei University College of Medicine, Seoul, Ch'ungch'ong-bukto, Republic of Korea; ⁵Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; ⁶Taipei Veterans General Hospital, Taipei, Taipei, Taiwan; ⁷Chinese University of Hong Kong Medical Centre, Hong Kong, Hong Kong; ⁸Toronto Liver Centre, Toronto, ON, Canada; ⁹Henry Ford Health System, Detroit, MI; ¹⁰Gilead Sciences, Inc., Foster City, CA; ¹¹Gilead Sciences, Gilbert, AZ; ¹²Gilead Sciences, Foster City, CA; ¹³Kaohsiung Medical University Hospital, Kaohsiung, Kaohsiung, Taiwan; ¹⁴University of Auckland, Auckland, Auckland, New Zealand; ¹⁵Asan Medical Center, Seoul, Seoul-t'ukpyolsi, Republic of Korea

Introduction: Switching to TAF, a novel tenofovir prodrug, has shown maintenance of viral suppression with stable or improved

bone and renal safety at Week 24 in CHB patients with moderate to severe renal impairment (eGFR by Cockcroft-Gault [eGFRCG] < 60 mL/min) and ESRD patients on HD. We evaluated the safety and efficacy in these virally suppressed patients with renal impairment 1 year after switching to TAF in a Phase 2 study.

Methods: CHB patients with renal impairment receiving TDF and/or other OAVs for ≥48 weeks and virally suppressed for ≥6 months with HBV DNA < 20 IU/mL at screening were enrolled into 2 cohorts: 1) moderate-severe renal impairment (eGFRCG 15 to < 60 mL/min) and 2) ESRD (eGFRCG < 15 mL/min) on chronic HD. All patients were switched to TAF 25 mg QD for 96 weeks (given post-HD on days of dialysis for ESRD patients). Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG], serum creatinine) parameters, viral suppression, and biochemical responses were assessed in all patients at Week 48.

Results: 93 patients (moderate-severe impairment 78; ESRD 15) were enrolled from 26 sites in 8 countries; 89% of patients remained on study at Week 48. At baseline, 74% were male, 77% Asian, 68% ≥60 y, 83% HBeAg-negative and median ALT was 17 U/L. Up to 25% overall (both cohorts) had osteoporosis at hip and/or spine, and a high proportion had comorbidities (60% HTN, 24% DM). Key efficacy/safety results at Week 48 are summarized in the Table. Efficacy (HBV DNA< 20 IU/mL) was maintained in nearly all patients on treatment at Week 48 and a high proportion had normal ALT levels. Five patients discontinued study drug early (withdrew consent) with last available HBV DNA < 20 U/mL; 1 patient had HBV DNA ≥20 IU/mL and 1 patient died. Relative to baseline levels, switching to TAF resulted in stable hip/spine BMD in moderate to severe renal impairment patients, with a slight decrease in hip BMD in ESRD patients. Slight improvements were observed in renal parameters including eGFRCG and markers of renal tubular function in moderate to severely impaired patients. TAF was well tolerated, with no Grade 3/4 or serious adverse events related to study drug.

Discussion: In renally-impaired CHB patients, including ESRD patients on HD, viral suppression was well maintained, and the bone and renal safety were stable or improved 48 weeks after switching to TAF.

	Moderate-Severe RI^a	ESRD on HD^_b
n/N (%) or median (Q1, Q3)	n=78	n=15
Efficacy
HBV DNA < 20 IU/mL	72/78 (92)^c	14/15 (93)^d
ALT normal (2018 AASLD criteria)	68/78 (87)	12/15 (80)
ALT normalization (2018 AASLD criteria)	3/5 (60)	NA
HBsAg loss	0/78 (0)	1/15 (7)
HBeAg loss	0/13 (0)	0/3 (0)
qHBsAg, log₁₀ change (IU/mL)	-0.04 (-0.10, 0.01)	-0.08 (-0.11, 0.01)
Bone parameters
Hip BMD, % change	+0.27 (-0.67, 1.40)	-1.74 (-3.85, 1.17)
Spine BMD, % change	+1.06 (-0.83, 3.28)	-0.04 (-1.76, 3.63)
CTX, % change, (ng/mL)^e	-20.5 (-38.5, 0.0)	-14.2 (-47.6, 11.4)
P1NP, % change (ng/mL)^f	-15.25 (-31.82, -0.76)	-20.55 (-35.62, 15.32)
Renal parameters
Serum creatinine, change mg/dL	+0.03 (-0.07, 0.08)	NA
Serum phosphorus, change mg/dL	0.0 (-0.1, 0.4)	NA
eGFR_CG, change mL/min	+0.8 (-3.9, 2.4)	NA
RBP/Cr, % change, μg/g^g	-42.4 (-67.4, -1.4)	NA
β2MG/Cr, % change, μg/g^h	-50.9 (-81.1, 51.8)	NA

Table: Table. Efficacy and safety results at Week 48
Efficacy results are missing equals failure (M=F)
a Moderate-severe renal impairment eGFRCG 15 - < 60 mL/min
b ESRD: eGFRCG < 15 mL/min on hemodialysis
c 5 patients discontinued study drug early (withdrew consent) with last available HBV DNA < 20 IU/mL;
1 patient had HBV DNA >=20 IU/mL
d 1 patient died
e Serum C-type collagen sequence (bone resorption marker); f Serum procollagen type 1 N-terminal propeptide (bone formation marker)
g Urine retinol binding protein/creatinine (renal tubular marker); h Urine beta-2 microglobulin/creatinine (renal tubular marker)
Abbreviations: eGFRCG, estimated creatinine clearance (Cockcroft-Gault method); ESRD, end-stage renal disease; BMD, bone mineral density by DXA scan); NA, not applicable

Disclosures:

Harry Janssen: Abbvie – Grant/Research Support. Alios – Consultant. Arbutus – Consultant, Grant/Research Support. Arena – Consultant. Bristol Myers Squibb – Grant/Research Support. Eiger – Consultant. Enyo – Consultant. Gilead Sciences – Consultant, Grant/Research Support. GlaxoSmithKline – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Consultant, Grant/Research Support. Regulus – Consultant. Roche – Consultant, Grant/Research Support. VBI Vaccines – Consultant. Vir Biotechnology – Consultant. Viroclinics – Consultant.

Jeong Heo indicated no relevant financial relationships.

Claire Fournier indicated no relevant financial relationships.

Sang Hoon Ahn indicated no relevant financial relationships.

Carla Coffin: Altimmune Pharmaceuticals – Grant/Research Support. Gilead Sciences – Grant/Research Support. GSK Pharmaceuticals – Grant/Research Support. Janssen Pharmaceuticals – Grant/Research Support.

Yi-Hsiang Huang indicated no relevant financial relationships.

Aric Josun Hui indicated no relevant financial relationships.

Magdy Elkhashab: Gilead Sciences – Advisory Committee/Board Member, Grant/Research Support.

Syed-Mohammed Jafri: Gilead, Abbvie, Takeda – Advisory Committee/Board Member, Speaker's Bureau.

Shuyuan Mo: Gilead Sciences, Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Jake Winans indicated no relevant financial relationships.

John Flaherty: Gilead Sciences – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Anuj Gaggar: Gilead Sciences – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Wan-Long Chuang: Gilead – Advisory Committee/Board Member, Consultant, Speaker's Bureau.

Ed Gane: Aligos – Advisory Committee/Board Member. Assembly – Advisory Committee/Board Member. Gilead – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member, Consultant.

Young-Suk Lim: Gilead Sciences – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's Bureau.

Harry Janssen, MD, PhD¹, Jeong Heo, MD, PhD², Claire Fournier, MD, PhD³, Sang Hoon Ahn, MD, PhD⁴, Carla S. Coffin, MD, MSc, FRCPC⁵, Yi-Hsiang Huang, MD, PhD⁶, Aric Josun Hui, MBCHB⁷, Magdy Elkhashab, MD, MSc, FRCPC⁸, Syed-Mohammed Jafri, MD⁹, Shuyuan Mo, PhD¹⁰, Jake Winans, MSN, RN, FNP-C¹¹, John Flaherty, PharmD¹⁰, Anuj Gaggar, MD¹², Wan-Long Chuang, MD¹³, Ed J. Gane, MBChB, MD¹⁴, Young-Suk Lim, MD, PhD¹⁵. P0741 - Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) in Virally Suppressed Chronic Hepatitis B (CHB) Patients With Renal Impairment: Week 48 Results From a Phase 2 Open-Label Study, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.