VEMLIDY demonstrated consistent efficacy in ALT1,2

Switch trial 4018 design

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

At Week 48, all patients who were randomized to TDF for the controlled portion of the trial were switched to VEMLIDY for the open-label extension through Week 96.8

See baseline characteristics

ALT measurements at baseline and Week 481,10,a,b

Chart showing normal ALT and ALT normalization at Week 48 for patients who switched to VEMLIDY® (tenofovir alafenamide) from TDF (tenofovir disoproxil fumarate) Chart showing normal ALT and ALT normalization at Week 48 for patients who switched to VEMLIDY® (tenofovir alafenamide) from TDF (tenofovir disoproxil fumarate)

ALT measurements at Week 968,b

Chart showing normal ALT and ALT normalization at Week 96 for patients who switched to VEMLIDY® (tenofovir alafenamide) from TDF (tenofovir disoproxil fumarate) Chart showing normal ALT and ALT normalization at Week 96 for patients who switched to VEMLIDY® (tenofovir alafenamide) from TDF (tenofovir disoproxil fumarate)

At Week 48, all patients who were in the TDF group in the controlled phase of the trial were switched to VEMLIDY which they used through Week 96 as part of the open-label extension phase. Patients who were originally assigned to VEMLIDY continued using it through Week 96.8

Adverse reactions observed with VEMLIDY in Trial 4018 were similar to those in Trials 108 and 110. Most common adverse reactions (incidence ≥5%, all grades) were headache, abdominal pain, cough, back pain, fatigue, nausea, arthralgia, diarrhea, and dyspepsia.1 AASLD=American Association for the Study of Liver Diseases; ALT=alanine aminotransferase; TAF=tenofovir alafenamide; TDF=tenofovir disoproxil fumarate; ULN=upper limit of normal. aAt baseline, median duration of prior TDF treatment was 220 weeks and 224 weeks in VEMLIDY and TDF groups, respectively. Week 48 window was between Day 295 and Day 378 (inclusive).1 bNormal ALT was defined as per the 2018 AASLD criteria: >35 and >25 U/L in men and women, respectively.1
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RESISTANCE

No HBV resistance with VEMLIDY in Trial 4018 through week 968

See the details

Genotypic resistance analysis was performed on patients experiencing HBV DNA ≥69 IU/mL at any study visit through Week 96.8

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.