VEMLIDY: A demonstrated renal safety profile

Across multiple trials, VEMLIDY demonstrated a reduced effect on renal safety parameters and improved renal function when compared to baseline.1,2

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).2-4,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 144.1 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

Effects of VEMLIDY and TDF were compared in a pooled analysis of Studies 108 and 110 (median baseline eGFRCG: 106 mL/min and 105 mL/min for each group, respectively)2:

  • In adult patients with chronic HBV, the mean increase in serum creatinine was <0.1 mg/dL in both treatment groups at both Week 96 and Week 1441,8
  • The median change in eGFRCG from baseline was smaller for VEMLIDY vs TDF

Change in eGFRCG from baseline at Week 1441

VEMLIDY
TDF
Median changes in eGFR CG from baseline for VEMLIDY® (tenofovir alafenamide) vs TDF (tenofovir disoproxil fumarate) Median changes in eGFR CG from baseline for VEMLIDY® (tenofovir alafenamide) vs TDF (tenofovir disoproxil fumarate)
  • Median change from baseline to Week 96 in eGFRCG was -1.2 mL/min in the VEMLIDY group (n=790) and -4.8 mL/min in those receiving TDF (n=390)1,2
AASLD=American Association for the Study of Liver Diseases; eGFRCG=estimated glomerular filtration rate by Cockcroft-Gault method, also referred to as eCrCl (estimated creatinine clearance); TDF=tenofovir disoproxil fumarate; ULN=upper limit of normal. cThe 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.1
  • The long-term clinical significance of these renal laboratory changes on adverse reaction frequencies between VEMLIDY and TDF is not known2

No renal dosage adjustment is required for VEMLIDY

  • For patients with mild, moderate, or severe renal impairmentd
  • For patients with ESRDe who are receiving chronic hemodialysis
    • On days of hemodialysis, administer VEMLIDY after completion of hemodialysis treatment
  • VEMLIDY is not recommended in patients with ESRD who are not receiving chronic hemodialysis
dEstimated creatinine clearance ≥15 mL/min.2 eEnd stage renal disease; estimated creatinine clearance <15 mL/min.2

Effects of VEMLIDY and TDF were compared in a pooled analysis of patients on open-label treatment from Week 96 through Week 144 (48-week safety data)1,2,f:

Improvement in eGFRCG in trials 108 and 110 at Week 144

Change in eGFRCG from baseline1,f

Chart showing change in eGFRCG from baseline at Week 144 for patients on VEMLIDY® (tenofovir alafenamide) compared to TDF (tenofovir disoproxil fumarate) Chart showing change in eGFRCG from baseline at Week 144 for patients on VEMLIDY® (tenofovir alafenamide) compared to TDF (tenofovir disoproxil fumarate)
fThe graph shows changes in eGFRCG from baseline for the subset population of patients who entered the open-label phase at Week 96.

Median change in eGFRCG from Week 96 to Week 1202

-0.6 mL/min
Patients who remained on VEMLIDY
+1.8 mL/min
Patients who switched from TDF to VEMLIDY
  • The long-term clinical significance of these renal laboratory changes on adverse reaction frequencies between VEMLIDY and TDF is not known2

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.