January 11, 2017
European Commission Grants Marketing Authorization for Gilead’s Vemlidy® (Tenofovir Alafenamide, TAF) for the Treatment of Chronic Hepatitis B Virus Infection
-- Vemlidy® is the First
New Treatment for Chronic Hepatitis B Infection to be Approved in the
The marketing authorization allows for the marketing of TAF in the 28
countries of the
“As the first new treatment for chronic hepatitis B to be approved in
TAF is a novel, targeted prodrug of tenofovir that has demonstrated antiviral efficacy similar to Gilead’s Viread® (tenofovir disoproxil fumarate, TDF) 245 mg, but at one-tenth the dose. Data show that because TAF has greater plasma stability and more efficiently delivers tenofovir to hepatocytes (cells of the liver) compared to TDF, it can be given at a lower dose, which means there is less tenofovir in the bloodstream. By reducing exposure to tenofovir, TAF is associated with improved renal and bone laboratory safety parameters compared to TDF in clinical trials.
“TAF reflects Gilead’s ongoing commitment to improve and simplify care
for people with chronic infectious diseases, including hepatitis B,
while we continue our research efforts for curative treatments,” said
TAF’s approval is supported by 48-week data from two international Phase 3 studies (Studies 108 and 110) in 1,298 adult chronic HBV patients. Study 108 randomized 425 HBeAg-negative patients to receive either TAF or TDF, and Study 110 randomized 873 HBeAg-positive patients to receive either TAF or TDF. Both studies met their primary endpoint of non-inferiority to TDF based on the percentage of patients with chronic hepatitis B with plasma HBV DNA levels below 29 IU/mL at 48 weeks of therapy. Patients in the TAF arm of the trials also experienced numerically higher rates of normalization of blood serum alanine aminotransferase (ALT) levels. Both studies showed TAF and TDF to be well-tolerated by patients and discontinuations due to adverse events were 1% and 1.2%, respectively. The most common reported adverse events with TAF were diarrhea, vomiting, nausea, abdominal pain, abdominal distension, flatulence, fatigue, headache, dizziness, rash, pruritus, increased ALT and arthralgia.
While the primary efficacy assessment was performed at week 48, data show that at week 72 viral suppression as well as biochemical responses were maintained with continued TAF treatment. The safety assessment includes analyses performed at both week 48 and week 72 of treatment (median duration of exposure of 88 weeks), and safety endpoints included changes from baseline in bone mineral density at the hip and spine, and changes from baseline in serum creatinine and in eGFR, key indicators of renal health. In both studies, at weeks 48 and 72, changes in renal and bone laboratory safety parameters favored the TAF treatment groups.
Vemlidy was approved by the
For important safety information for TAF in
Important Safety Information and Indication for Vemlidy in the U.S.
BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B
- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs.
- 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 is not recommended 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
Renal monitoring: Assess serum creatinine, serum phosphorus, CrCl, urine glucose, and urine protein prior to initiating and during therapy in all patients as clinically appropriate.
Most common adverse reactions (incidence ≥5%; all grades) were headache, abdominal pain, fatigue, cough, nausea and back pain.
- 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-gp and 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
- Dosage: Adults; 1 tablet taken once daily with food.
- Renal Impairment: Not recommended in patients with CrCl <15 mL/min.
- Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment.
- Testing prior to initiation: HIV infection.
VEMLIDY is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease.
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995, that
are subject to risks, uncertainties and other factors, including the
risk that physicians may not see the benefits of prescribing Vemlidy.
These risks, uncertainties and other factors could cause actual results
to differ materially from those referred to in the forward-looking
statements. The reader is cautioned not to rely on these forward-looking
statements. These and other risks are described in detail in Gilead’s
Quarterly Report on Form 10-Q for the quarter ended
The European SmPCs for Vemlidy and Viread are available from the EMA website at www.ema.europa.eu.
Vemlidy and Viread are registered trademarks of
For more information on
Gilead Sciences, Inc.
Sung Lee, +1 650-524-7792
Kelsey Grossman, +1 650-378-2103