VEMLIDY was 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 VEMLIDY 25 mg once daily in the treatment of CHB in adults with compensated liver disease were evaluated in 2 randomized, double-blind, active-controlled, noninferiority trials: Trial 108 (N=425 HBeAg– treatment-naïve and treatment-experienced patients) and Trial 110 (N=873 HBeAg+ treatment-naïve and treatment-experienced patients).1-3,b

The primary efficacy endpoint for both trials was the proportion of patients with plasma HBV DNA levels below 29 IU/mL at Week 48. Additional efficacy endpoints evaluated at Week 48, Week 96, and Week 144 for both studies include the proportion of patients with HBV DNA <>9 IU/mL, alanine aminotransferase (ALT) normalization, and hepatitis B surface antigen (HBsAg) loss and seroconversion. Hepatitis B envelope antigen (HBeAg) loss and seroconversion were also assessed in Trial 110.1-4 In the original protocol, patients were randomized to VEMLIDY or TDF 300 mg once daily in the double-blind phase for 96 weeks, followed by an open-label VEMLIDY phase through Week 144.4 The original protocol was amended to extend the double-blind phase from 96 weeks to 144 weeks, followed by an open-label phase through Week 384.6 However, before implementation of the amendment protocol, 540 patients entered the open-label phase at Week 96 (n=360 remained on VEMLIDY and n=180 switched from TDF to VEMLIDY).c At Week 144, all 1,137 remaining HBeAg– and HBeAg+ patients (out of the original 1,298) entered the open-label VEMLIDY phase for an extension trial that is still ongoing.5

bKey inclusion criteria: HBV DNA >20,000 IU/mL; ALT >60 U/L for men and >38 U/L for women (2x ULN based on the 2016 AASLD criteria).3,7

cThe 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 trial treatment by Week 96.5

Studies 108 & 110: Pooled Population
Baseline Characteristics4,6 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)
HBV genotype A, B, C, D, % 6, 18, 48, 26 7, 20, 46, 24
Mean HBV DNA, log10 IU/mL (SD) 7.0 (1.8-9.9) 7.0 (1.4-9.9)
Median ALT, U/L (Q1, Q3) 80 (56, 123) 80 (53, 130)
Treatment-experienced, n (%) 211 (24) 108 (25)
History of cirrhosis, n (%)d 65/636 (10) 38/326 (12)
Prior oral antiviral therapy, n (%)e
Entecavir 109 (13) 49 (11)
Lamivudine 86 (10) 40 (9)
Adefovir dipivoxil 35 (194) 14 (3)
Telbivudine 21 (2) 12 (3)
Otherf 14 (2) 6 (1)
Hip BMD status, n (%)
Normal 570 (67) 285 (67)
Osteopenia 256 (30) 131 (31)
Osteoporosis 12 (1) 2 (<1)
Not determined 13 (2) 8 (2)
Spine BMD status, n (%)
Normal 477 (55) 237 (56)
Osteopenia 309 (36) 152 (36)
Osteoporosis 57 (7) 29 (7)
Not determined 13 (2) 8 (2)
ALT= alanine aminotransferase; BMD=bone mineral density; HBV DNA=hepatitis B virus deoxyribonucleic acid; TDF=tenofovir disoproxil fumarate. dExcludes patients with missing values.6 eExcluding interferon and TDF.4 fIncludes clevudine, tenofovir alafenamide, and other oral nucleoside/nucleotide agents.4

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.