VEMLIDY VS TDF: IMPROVED ALT NORMALIZATION RATES

CLINICAL STUDY DESIGN

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 studies, Study 108 (N=425 HBeAg−) and Study 110 (N=873 HBeAg+). The original study design consisted of a 96-week, double-blind phase followed by an open-label phase to Week 144. The original study design was then amended to extend the double-blind phase from 96 to 144 weeks and the open-label phase to Week 384. However, before the amendment to the double-blind phase was implemented, 540 patients had already entered the open-label phase at Week 96; 360 patients remained on VEMLIDY 25 mg and 180 patients switched from TDF (tenofovir disoproxil fumarate) 300 mg to VEMLIDY 25 mg at Week 96.1-3

The primary endpoint for both studies was HBV DNA <29 IU/mL and noninferiority to TDF (10% margin; 95% CI approach) at Week 48; this was also one of the key secondary endpoints at Weeks 96 and 144.1-8,a Learn more about the VEMLIDY clinical study design

aEfficacy endpoints evaluated at Week 48, Week 96, and Week 144 for both studies include the proportion of patients with HBV DNA <29 IU/mL, ALT normalization, and HBsAg loss and seroconversion. HBeAg loss and seroconversion were also assessed in Study 110. Key inclusion criteria: HBV DNA ≥20,000 IU/mL; ALT>60 U/L (males) or >38 U/L (females) and ≤10× ULN by central laboratory range.1-3,8

ALT NORMALIZATION RATES THROUGH WEEK 144

VEMLIDY showed improved rates of ALT normalization in treatment-naïve and treatment-experienced patients with compensated liver disease.1-5,7,8

ALT normalization (2016 AASLD criteria)b,c


Charts showing ALT normalization for VEMLIDY® (tenofovir alafenamide) vs TDF in Study 108 and Study 110 Charts showing ALT normalization for VEMLIDY® (tenofovir alafenamide) vs TDF in Study 108 and Study 110
Charts showing ALT normalization for VEMLIDY® (tenofovir alafenamide) vs TDF in Study 108 and Study 110 Charts showing ALT normalization for VEMLIDY® (tenofovir alafenamide) vs TDF in Study 108 and Study 110
TDF=tenofovir disoproxil fumarate. bThe 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 cPatient 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.8

KIMBERLY BROWN, MD, FAASLD, FAST, AGAF

Chief of the Division of Gastroenterology and Hepatology
Henry Ford Hospital, Detroit, Michigan

Explore additional results from the VEMLIDY pivotal clinical trials in this presentation by Dr. Brown.

Explore additional results from the pivotal clinical trials in this video presentation by Kimberly Brown, MD, FAASLD, FAST, AGAF. Dr. Brown is Chief of the Division of Gastroenterology and Hepatology at Henry Ford Hospital in Detroit, Michigan.

  1. Agarwal K, Brunetto M, Seto WK, et al. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018;68:672-681.
  2. American Association for the Study of Liver Diseases. Posters (Abstracts 301-2389). Hepatology. 2018;68:S184-S1353.
  3. Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1:196-206.
  4. Chan HLY, Fung S, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1:185-195.
  5. Chan HLY, Lim YS, Seto WK, et al. 3-year efficacy and safety of tenofovir alafenamide compared with tenofovir disoproxil fumarate in HBeAg-negative and -positive patients with chronic hepatitis B. Poster presented at: AASLD 2018; November 9-13, 2018; San Francisco, CA. Poster 381.
  6. Chan HLY, Marcellin P, Pan CQ, et al. No resistance to tenofovir alafenamide detected through 144 weeks of treatment in patients with chronic hepatitis B. Poster presented at: AASLD 2018; November 9-13, 2018; San Francisco, CA. Poster 386.
  7. Data on file. Gilead Sciences, Inc.
  8. Seto WK, Buti M, Izumi N, et al. Bone and renal safety are improved in chronic HBV patients 1 year after switching to tenofovir alafenamide from tenofovir disoproxil fumarate. Poster presented at: AASLD 2018; November 9-13, 2018; San Francisco, CA. Poster 404.
  9. VEMLIDY Prescribing Information, Foster City, CA: Gilead Sciences, Inc.; February 2019.
0 %
RESISTANCE No HBV resistance with VEMLIDY
through Week 1441,4,7,9
SEE THE DETAILS

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: 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.