Vemlidy (Tenofovir Alafenamide) for Treatment of Chronic Hepatitis B Virus Infection, United States of America
Developed by Gilead Sciences, Vemlidy (Tenofovir Alafenamide) is indicated for treatment of Hepatitis B virus infection with compensated liver disease in adult patients.
The new drug application (NDA) for Vemlidy was submitted to the US Food and Drug Administration (FDA) on 11 January 2016. The FDA granted approval for Vemlidy on 10 November 2016.
Marketing authorisation application for Vemlidy was submitted to the European Medical Agency (EMA) on 25 February 2016 and the same is under review.
Gilead has also filed NDA for Vemlidy with the Japan's Pharmaceutical and Medical Devices Agency on 31 March 2016 and the same is currently under review.
Hepatitis B infection causes and symptoms
Hepatitis B virus infects the liver and causes infectious hepatitis. The disease is communicable and the virus is spread from person to person through sharing needles or syringes, sexual intercourse, or from mother to baby during birth.
Acute hepatitis B is a short-term illness and shows symptoms within six months from exposure to HBV, whereas chronic hepatitis B is a long-term illness and usually occurs if the virus remains in the body for a longer time after being exposed to the infection.
Chronic liver infection is associated with symptoms such as loss of appetite, nausea, vomiting, fatigue, severe abdominal pain, jaundice, dark coloured urine and joint pains.
Vemlidy's mechanism of action
Vemlidy is a 25mg once a day oral formulation for treatment of adult patients with chronic hepatitis B virus infection.
Tenofovir Alafenamide is a lipophilic cell permeant compound, which enters the liver cells (hepatocytes) through passive diffusion and with the help of hepatic uptake transporters OATP1B1 and OATP1B3. In the hepatocytes, Tenofovir Alafenamide gets hydrolysed to tenofovir, which in turn gets phosphorylated to tenofovir diphosphate.
Tenofovir diphosphate gets incorporated into the viral DNA by HBV reverse transcriptase and inhibits the growth of the virus by halting the HBV replication.
The US FDA approved Vemlidy based on the results obtained from two phase 3 clinical trials, study 108 and Study 110 conducted on 1,298 subjects with hepatitis B infection to evaluate the safety and efficacy of the drug.
Study 108 was a 48-week, randomised, double-blind, active-controlled and phase 3 trial conducted on 425 subjects with HBeAg-negative treatments naive and treatment-experienced with compensated liver disease. Subjects were randomised to receive either Vemlidy 25mg once a day for 48 weeks or tenofovir disoproxil fumarate 300mg once a day for 48 weeks.
Study 110 was a 48-week, randomised, double-blind, active-controlled trial conducted on 873 subjects with HBeAg-negative treatments naive and treatment-experienced with compensated liver disease. Subjects in the trial were randomised to receive either Vemlidy 25mg once a day for 48 weeks or tenofovir disoproxil fumarate 300mg once a day for 48 weeks.
The two studies met the primary end points and indicated that Vemlidy was superior to tenofovir disoproxil fumarate in showing non-inferiority HBV DNA levels below 29IU/ml through the 48 weeks and normalisation of blood serum alanine aminotransferase (ALT) levels.
Further analysis of both studies has shown that patients who received Vemlidy have improved bone and renal laboratory parameters when compared with patients who took tenofovir disoproxil fumarate.
The most commonly observed adverse events in the two studies were headache, cough, abdominal pain, fatigue, nausea and back pain.