VEMLIDY: An improved bone safety profile
Across multiple trials, VEMLIDY demonstrated both reduced impact and improvements in bone mineral density.1,2
VEMLIDY showed reduced impact on BMD at Week 144
Impacts on spine and hip BMD with VEMLIDY and TDF were compared in Trials 108 and 110.
Change in lumbar spine BMD from baseline at Week 144 (pooled)2,a
Change in total hip BMD from baseline at Week 144 (pooled)2,a
The long-term clinical significance of these BMD changes is not known.1
The mean percentage change in BMD from baseline to Week 96 was -0.7% with VEMLIDY (n=746) compared to -2.6% with TDF (n=371) at the lumbar spine, and -0.3% (n=740) compared to -2.5% (n=369) at the total hip.1,2
DXA=dual-energy X-ray absorptiometry; HBeAg=hepatitis B envelope antigen.
aThe Week 144 analysis did not include the 180 subjects (HBeAg−: 66 subjects; HBeAg+: 114 subjects) who had rolled over from double-blind TDF to open-label VEMLIDY at Week 96 prior to the trial amendment.2
bOnly subjects with nonmissing baseline data for spine or hip BMD were included in the spine or hip DXA analysis set.2
Long-term BMD remained stable at Year 5 in patients taking VEMLIDY
Pooled Safety Analysis (Week 240): Pooled safety analysis (observed data) from Trials 108 and 110 was assessed at Week 240. This analysis includes 866 subjects who initiated VEMLIDY at baseline,c 180 subjects who switched from TDF to TAF at Week 96, and 202 subjects who switched from TDF to TAF at Week 144.2
Mean percentage change in lumbar spine BMD from Week 96 to Week 120: +0.6% in subjects who remained on VEMLIDY; +1.7% in those who switched from TDF to VEMLIDY.1
SD=standard deviation; TAF=tenofovir alafenamide.
bOnly subjects with nonmissing baseline data for spine or hip BMD were included in the spine or hip DXA analysis set.
cVEMLIDY group includes VEMLIDY subjects who rolled over to open-label VEMLIDY at Week 96 or Week 144.2
The long-term clinical significance of these BMD changes is not known.1
Spine BMD remained stable in VEMLIDY patients, and there was an improvement seen in patients who switched to VEMLIDY from TDF.2
~75% of patients enrolled in pivotal trials 108/110 were treatment-naive.2
The 5-year data is not presented in the VEMLIDY label.
Mean percentage change in total hip BMD from Week 96 to Week 120: 0% in subjects who remained on VEMLIDY; +0.6% in those who switched from TDF to VEMLIDY.1
bOnly subjects with nonmissing baseline data for spine or hip BMD were included in the spine or hip DXA analysis set.
cVEMLIDY group includes VEMLIDY subjects who rolled over to open-label VEMLIDY at Week 96 or Week 144.2
The long-term clinical significance of these BMD changes is not known.1
Hip BMD remained stable in VEMLIDY patients, and there was an improvement seen in patients who switched to VEMLIDY from TDF.2
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.
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.
