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.

Pivotal trials and open-label extension (OLE): 108 and 110
~75% of patients enrolled in pivotal trials 108/110 were treatment-naïve8

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 trials.2,6,b

bKey inclusion criteria: HBV DNA ≥20,000 IU/mL; ALT >60 U/L (males) or >38 U/L (females) and ≤10x ULN by central laboratory range.2,6

Chart efficacy Chart efficacy

ALT=alanine aminotransferase; HBeAg=hepatitis B envelope antigen; TDF=tenofovir disoproxil fumarate; ULN=upper limit of normal. cThe numbers of subjects listed after Week 96 refers to those who entered the open-label phase or remained in the double-blind phase, and excludes subjects who prematurely discontinued double-blind study treatment by Week 96.8,9

Trial 108 (N=425)1

  • HBeAg- subjects (79% treatment-naïve patients, 21% treatment-experienced patients)1,8

Trial 110 (N=873)1

  • HBeAg+ subjects (74% treatment-naïve patients, 26% treatment-experienced patients)1,8

The primary endpoint for both studies was HBV DNA <29 IU/mL and noninferiority to TDF (10% margin; 95% confidence interval [CI] approach) at Week 48.2,6

Additional efficacy endpoints evaluated at Week 48, Week 96, and Week 144 for both studies include1,2,6,8:

  • Proportion of patients with HBV DNA <29 IU/mL
  • ALT normalization
  • HBsAg loss and seroconversion

HBeAg loss and seroconversion were also assessed in Trial 110.1

The original protocol was amended to extend the double-blind phase from 96 weeks to 144 weeks. However, before implementation of the amendment protocol, 540 patients entered the open-label phase at Week 96 (360 patients remained on VEMLIDY and 180 patients switched from TDF to VEMLIDY).1,8

At Week 144, all 1137 remaining HBeAg– and HBeAg+ patients (out of the original 1298) entered the open-label VEMLIDY phase for an extension trial that is still ongoing.1,8

The 5-year data is not presented in the VEMLIDY label.

Table trial Designs Table trial Designs
Treatment-naïve subjects had <12 weeks of previous treatment with any nucleoside/nucleotide analog. Treatment-experienced subjects met all entry criteria (including HBV DNA ≥20,0000 IU/mL and serum ALT criteria) and had ≥12 weeks of previous treatment with any nucleoside/nucleotide analog.1,8 BMD=bone mineral density; HBsAg=hepatitis B surface antigen. dExcludes patients with missing values.8 eExcluding interferon and TDF. f“Other” category included clevudine, tenofovir alafenamide, and other oral nucleos(t)ide agents.8

Warnings and Precautions

  • New Onset or Worsening Renal Impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with TAF-containing products. 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: POSTTREATMENT 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: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with TAF-containing products. 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 disoproxil fumarate (TDF). 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) in clinical studies through week 144 were headache, upper respiratory tract infection, abdominal pain, cough, back pain, arthralgia, fatigue, nausea, diarrhea, dyspepsia, and pyrexia.

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 see full Prescribing Information for VEMLIDY, including BOXED WARNING.