VEMLIDY: PROVEN IN ROBUST, GLOBAL CLINICAL TRIALS

The efficacy and safety of VEMLIDY in the treatment of adults with chronic HBV infection with compensated liver disease are based on data from 2 randomized, double-blind, active-controlled, noninferiority studies with 1298 patients (HBeAg– and HBeAg+).1,2,3,a

The efficacy endpoint in both studies was the proportion of patients with plasma HBV DNA levels <29 IU/mL at Week 48.1

Studies 108 & 110—Important changes to study protocol1-7

VEMLIDY® (tenofovir alafenamide) vs TDF (tenofovir disoproxil fumarate) original design
  • The original study design consisted of a 96-week, double-blind phase followed by an open-label phase to Week 144
VEMLIDY® (tenofovir alafenamide) vs TDF (tenofovir disoproxil fumarate) amended design
  • The original study design for Studies 108 and 110 was amended to extend the double-blind phase from 96 to 144 weeks and the open-label phase to Week 384
VEMLIDY® (tenofovir alafenamide) vs TDF (tenofovir disoproxil fumarate) current design
  • However, before the amendment to the double-blind phase was implemented, 540 patients had already entered the open-label phase at Week 96; 360 patients remained on VEMLIDY and 180 patients switched from TDF to VEMLIDY at Week 96
    • The numbers of patients listed after Week 96 refer to those who entered the open-label phase or remained in the double-blind phase, and excluded patients who prematurely discontinued double-blind study treatment by Week 96

The primary endpoint for both studies was HBV DNA <29 IU/mL and noninferiority to TDF (10% margin; 95% CI approach) at Week 48; this was also one of the key secondary endpoints at Weeks 96 and 144.1-8,c

TDF=tenofovir disoproxil fumarate. DB=double-blind; OL=open-label aStudy 108 included 425 HBeAg− patients; Study 110 included 873 HBeAg+ patients.1 bThe numbers of patients listed after Week 96 refer to those who entered the open-label phase or remained in the double-blind phase, and exclude patients who prematurely discontinued double-blind study treatment by Week 96.8 cEfficacy endpoints evaluated at Week 48, Week 96, and Week 144 for both studies include the proportion of patients with HBV DNA <29 IU/mL, ALT normalization, and HBsAg loss and seroconversion. HBeAg loss and seroconversion were also assessed in Study 110. Key inclusion criteria: HBV DNA ≥20,000 IU/mL; ALT >60 U/L (males) or >38 U/L (females) and ≤10× ULN by central laboratory range.1-3,8

Warnings and Precautions

  • New Onset or Worsening Renal Impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of VEMLIDY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients – See Dosage and Administration.
Studies 108 & 110:
Pooled Population
Baseline Characteristics4,8 VEMLIDY
(N=866)
TDF
(N=432)
Mean age, y (range) 40 (18-80) 41 (18-72)
Male, n (%) 544 (63) 275 (64)
Asian, n (%) 687 (79) 333 (77)
White, n (%) 167 (19) 87 (20)
Black, n (%) 7 (1) 6 (1)
Other, n (%) 5 (<1) 6 (1)
HBeAg+, n (%) 569 (66) 290 (67)
HBV genotype A, B, C, D, % 6, 18, 48, 26 7, 20, 46, 24
Mean HBV DNA, log10 IU/mL (SD) 7.0 (1.6) 7.0 (1.6)
Median ALT, U/L (Q1, Q3) 80 (56, 123) 80 (53, 130)
Treatment-experienced, n (%)d 211 (24) 108 (25)
History of cirrhosis, n (%) 65/636 (10) 38/326 (12)
Median eGFRCG, mL/min (Q1, Q3) 106 (91, 125) 105 (90, 124)
Normal BMD status
(T-score ≥-1.0), n (%)
Hip 570 (67) 285 (67)
Spine 477 (56) 237 (56)
Patients Who Switched
to Open-label VEMLIDY at
Week 96: Pooled Data
Baseline Characteristics4,8 VEMLIDY
(N=360)
TDF
(N=180)
Mean age, y (range) 40 (19-73) 42 (18-67)
Male, n (%) 228 (63) 111 (62)
Asian, n (%) 292 (81) 146 (81)
White, n (%) 60 (17) 30 (17)
Black, n (%) 4 (1) 2 (1)
Other, n (%) 2 (1) 2 (1)
HBeAg+, n (%) 221 (61) 114 (63)
HBV genotype A, B, C, D, % 6, 25, 48, 20 6, 27, 44, 20
Mean HBV DNA, log10 IU/mL (SD) 6.9 (1.5) 7.0 (1.6)
Median ALT, U/L (Q1, Q3) 84 (56, 127) 81 (54, 136)
Treatment-experienced, n (%)d 85 (24) 43 (24)
History of cirrhosis, n (%) 25/258 (10) 16/131 (12)
Median eGFRCG, mL/min (Q1, Q3) 105 (90, 122) 104 (86, 125)
Normal BMD status
(T-score ≥-1.0), n (%)
Hip 236 (66) 112 (63)
Spine 205 (57) 93 (52)
Studies 108 & 110:
Pooled Population
Patients Who Switched
to Open-label VEMLIDY at
Week 96: Pooled Data
Baseline Characteristics4,8 VEMLIDY
(N=866)
TDF
(N=432)
VEMLIDY
(N=360)
TDF
(N=180)
Mean age, y (range) 40 (18-80) 41 (18-72) 40 (19-73) 42 (18-67)
Male, n (%) 544 (63) 275 (64) 228 (63) 111 (62)
Asian, n (%) 687 (79) 333 (77) 292 (81) 146 (81)
White, n (%) 167 (19) 87 (20) 60 (17) 30 (17)
Black, n (%) 7 (1) 6 (1) 4 (1) 2 (1)
Other, n (%) 5 (<1) 6 (1) 2 (1) 2 (1)
HBeAg+, n (%) 569 (66) 290 (67) 221 (61) 114 (63)
HBV genotype A, B, C, D, % 6, 18, 48, 26 7, 20, 46, 24 6, 25, 48, 20 6, 27, 44, 20
Mean HBV DNA, log10 IU/mL (SD) 7.0 (1.6) 7.0 (1.6) 6.9 (1.5) 7.0 (1.6)
Median ALT, U/L (Q1, Q3) 80 (56, 123) 80 (53, 130) 84 (56, 127) 81 (54, 136)
Treatment-experienced, n (%)d 211 (24) 108 (25) 85 (24) 43 (24)
History of cirrhosis, n (%) 65/636 (10) 38/326 (12) 25/258 (10) 16/131 (12)
Median eGFRCG, mL/min (Q1, Q3) 106 (91, 125) 105 (90, 124) 105 (90, 122) 104 (86, 125)
Normal BMD status
(T-score ≥-1.0), n (%)
Hip 570 (67) 285 (67) 236 (66) 112 (63)
Spine 477 (56) 237 (56) 205 (57) 93 (52)
dExcluding interferon.8 ALT=alanine aminotransferase; BMD=bone mineral density; CI=confidence interval; eGFRCG=eGFR by Cockcroft-Gault method, also referred to as eCrCl (estimated creatinine clearance); HBeAg=hepatitis B envelope antigen; HBsAg=hepatitis B surface antigen; HBV DNA=hepatitis B virus deoxyribonucleic acid; Q1, Q3=quartile 1, quartile 3; SD=standard deviation; ULN=upper limit of normal.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: POST TREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B

  • Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

Warnings and Precautions

  • Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone should not be used for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and, if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used.
  • New Onset or Worsening Renal Impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of VEMLIDY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients – See Dosage and Administration.
  • Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including tenofovir DF. Discontinue VEMLIDY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse Reactions

Most common adverse reactions (incidence ≥5%; all grades) were headache, abdominal pain, cough, back pain, fatigue, nausea, arthralgia, diarrhea, and dyspepsia.

Drug Interactions

  • Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions.
  • Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) activity may lead to changes in VEMLIDY absorption.

Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments.

Dosage and Administration

  • Testing Prior to Initiation: HIV infection.
  • Prior to or when initiating, and during treatment: On a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.
  • Dosage in Adults: 1 tablet taken once daily with food.
  • Renal Impairment: Not recommended in patients with end stage renal disease (ESRD; eCrCl <15 mL/min) who are not receiving chronic hemodialysis; in patients on chronic hemodialysis, on hemodialysis days, administer VEMLIDY after completion of hemodialysis treatment.
  • Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment.

INDICATION

VEMLIDY is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease.

Please click here to see full Prescribing Information for VEMLIDY, including BOXED WARNING.