VEMLIDY: PROVEN IN ROBUST, GLOBAL CLINICAL TRIALS

The efficacy and safety profile of VEMLIDY in the treatment of adults with chronic HBV infection with compensated liver disease was based on data from 3 randomized, double-blind, active-controlled trials with 1786 patients (HBeAg– and HBeAg+).1-7,a

aStudy 4018 included 488 virologically suppressed patients; Study 108 included 425 HBeAg− patients; Study 110 included 873 HBeAg+ patients.

Trial design and baseline characteristics

The efficacy and safety of switching from TDF 300 mg once daily to VEMLIDY 25 mg once daily in virologically suppressed adults with CHB infection were evaluated in a randomized, double-blind, active-controlled trial: Trial 4018 (N=488). Patients must have been taking TDF 300 mg once daily for ≥12 months, with HBV DNA less than the Lower Limit of Quantitation by local laboratory assessment ≥12 weeks prior to screening and HBV DNA >20 IU/mL at screening. Patients were randomized in a 1:1 ratio to either switch to VEMLIDY (n=243) or stay on TDF (n=245). At baseline, the median duration of exposure to TDF prior to the trial was similar in both treatment groups (TAF=220.0 weeks, TDF=224.3 weeks).

The primary efficacy endpoint was the proportion of patients with plasma HBV DNA ≥20 IU/mL at Week 48. Additional efficacy endpoints included the proportion of patients with HBV DNA >20 IU/mL, ALT normal and normalization, HBsAg loss and seroconversion, and HBeAg loss and seroconversion.1

Baseline Characteristics4 VEMLIDY (N=243) TDF (N=245)
Mean age, y (SD) 51 (10.5) 51 (10.8)
Male, n (%) 179 (74) 166 (68)
Asian, n (%) 195 (80) 205 (84)
HBeAg+, n (%) 78 (32) 79 (32)
History of cirrhosis, n (%)b 32/233 (14) 45/235 (19)
Prior oral antiviral therapy, n (%)c
Lamivudine 95 (39) 96 (39)
Adefovir dipivoxil 94 (39) 91 (37)
Entecavir 47 (19) 52 (21)
Telbivudine 21 (9) 27 (11)
Otherd 13 (5) 11 (4)
Hip BMD status, n (%)
Normal 143 (59) 124 (51)
Osteopenia 89 (37) 116 (48)
Osteoporosis 9 (4) 4 (2)
Spine BMD status, n (%)
Normal 125 (51) 120 (49)
Osteopenia 90 (37) 97 (40)
Osteoporosis 28 (12) 28 (11)
CHB=chronic hepatitis B; HBeAg=hepatitis B envelope antigen; HBV DNA=hepatitis B virus deoxyribonucleic acid; TAF=tenofovir alafenamide; TDF=tenofovir disoproxil fumarate. bExcludes patients with missing values. cExcludes TDF. dIncludes clevudine, emtricitabine/TDF, and tenofovir alafenamide.

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.

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.