Product Theater: Vemlidy for Hepatitis B

Chronic hepatitis B virus (HBV), which affects an estimated 862,000 individuals in the United States, is caused by long-term infection with the virus and can lead to serious liver damage. During a product theater at the 2019 National Association of Specialty Pharmacy Annual Meeting and Expo, speaker Elena Doan, PharmD, CSP, Specialty Programs manager at Paragon Healthcare, Inc, outlined how HBV impacts patients and the effect of treatment with tenofovir alafenamide (Vemlidy).

HBV is transmitted via bodily fluids from a person infected with the virus through sexual contact, by sharing syringes, or from a mother to her baby at birth. In some people, HBV is a short-term illness, while in others it could become a long-term chronic infection, which is associated with their age at the time of infection. Approximately 90% of infants with HBV develop chronic infection compared with 2% to 6% of adults.¹

Approximately 25% of patients with HBV who develop a chronic infection during childhood and 15% of those who become chronically infected after childhood die prematurely from cirrhosis or liver cancer. The majority of patients with HBV are asymptomatic until onset of cirrhosis or end-stage liver disease. A total of 1715 deaths related to HBV infection were reported to the CDC in 2015; however, the CDC estimates that annual deaths related to HBV are closer to approximately 14,000.¹

Tenofovir alafenamide is a nucleoside analog reverse transcriptase inhibitor specifically indicated to treat HBV in adults with compensated liver disease; it is a novel, targeted phosphonamidate prodrug of tenofovir. Because tenofovir does not readily cross cell membranes and is poorly absorbed, prodrugs of tenofovir are needed to increase its cellular permeability and oral bioavailability.² Tenofovir alafenamide is administered as a 25-mg tablet taken once daily with food.

The FDA approval of tenofovir alafenamide was based on results from a pair of international phase 3 trials, Studies 108 and 110, which included 1298 treatment-naïve and treatment-experienced adult patients with chronic HBV infection. Study 108 randomized and treated 425 hepatitis B e antigen (HBeAg)-negative patients with either 25 mg tenofovir alafenamide or 300-mg tenofovir disoproxil fumarate (Viread), whereas Study 110 randomized and treated 873 HBeAgpositive patients with either 25-mg tenofovir alafenamide or 300-mg tenofovir disoproxil fumarate.

Both studies achieved the primary end points that established the noninferiority of tenofovir alafenamide to tenofovir disoproxil fumarate based on percentage of patients with plasma HBV DNA levels below 29 IU/mL at 48 weeks of therapy: 94% versus 93%, respectively, for patients in Study 108 and 64% versus 67%, respectively, for Study 110.2

In an integrated analysis of both studies, patients in the tenofovir alafenamide treatment group showed improvements in certain bone and renal laboratory parameters compared with the tenofovir disoproxil fumarate treatment arm. Furthermore, patients treated with tenofovir alafenamide experienced numerically higher rates of normalization of blood serum alanine aminotransferase levels.²

Less than one-third of the patients experienced adverse events (AEs), with a maximum of 10 serious AEs reported in both trials, none of which were considered to be related to treatment. The most common AEs were headache, abdominal pain, fatigue, cough, nausea, and back pain.² No resistance to tenofovir alafenamide was detected through week 144.²

References

• CDC.gov. (2019). Hepatitis B Questions and Answers for Health Professionals. CDC. [online] Available at: cdc.gov/hepatitis/hbv/hbvfaq.htm#overview. Accessed September 26, 2019.
• Vemlidyhcp.com. (2019). VEMLIDY® (tenofovir alafenamide) Clinical Trial Design | HCP Site. [online] Available at: https://www.vemlidyhcp.com/clinical_trial_design. Accessed September 26, 2019.