VEMLIDY demonstrated consistent efficacy in ALT1,2

Pivotal trials 108 & 110 design

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).1,3,4,a

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 <29 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 144.2 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 384.5 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).b 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.6

See baseline characteristics

aKey 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).4,7
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 trial treatment by Week 96.6

ALT normalization rates at Week 48, 96, and 144 (2016 AASLD criteria)c,d

VEMLIDY
TDF
 Chart showing ALT normalization for VEMLIDY® (tenofovir alafenamide) vs TDF (tenofovir disoproxil fumarate) in HBeAg- CChart showing ALT normalization for VEMLIDY® (tenofovir alafenamide) vs TDF (tenofovir disoproxil fumarate) in HBeAg-
Chart showing ALT normalization for VEMLIDY® (tenofovir alafenamide) vs TDF (tenofovir disoproxil fumarate) in HBeAg+ Chart showing ALT normalization for VEMLIDY® (tenofovir alafenamide) vs TDF (tenofovir disoproxil fumarate) in HBeAg+
  • At Week 48: ALT normalization was 50% (137/276) for VEMLIDY vs 32% (44/138) for TDF in Trial 108 and 45% (257/572) for VEMLIDY vs 36% (105/290) for TDF in Trial 110.1-3
  • At Week 96: ALT normalization was 50% (139/276) for VEMLIDY vs 40% (55/138) for TDF in Trial 108 and 52% (299/572) for VEMLIDY vs 42% (121/290) for TDF in Trial 110.4
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. AASLD=American Association for the Study of Liver Diseases; TDF=tenofovir disoproxil fumarate; ULN=upper limit of normal. cThe population used for analysis of ALT normalization included only patients with ALT >ULN per the 2016 AASLD criteria (>30 U/L for males and >19 U/L for females) at baseline.1 dPatient populations analyzed included all patients who were randomized into the study and received at least 1 dose of study drug; a missing=failure approach was used. The Week 144 analysis did not include the 66 patients from the TDF group in Study 108 and the 114 patients from the TDF group in Study 110 who had rolled over from double-blind TDF to open-label VEMLIDY at Week 96 prior to the study amendment.2
0 %
RESISTANCE

No HBV resistance with VEMLIDY in trials 108 and 110 through Week 1441,5,8,9

See the details

Genotypic resistance analysis was performed on patients experiencing either1: - Virologic breakthrough (2 consecutive visits with HBV DNA ≥69 IU/mL [400 copies/mL] after having been <69 IU/mL, or 1.0-log10 or greater increase in HBV DNA from nadir) - HBV DNA ≥69 IU/mL at early discontinuation at or after Week 24

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.

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.