General Information

Vemlidy (tenofovir alafenamide) is a hepatitis B virus nucleoside analog reverse transcriptase inhibitor.

Vemlidy is specifically indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease. Approval was expanded in November of 2022 to include pediatric patients 12 years of age and older with compensated liver disease.

Vemlidy is supplied as a tablet for oral administration.

Adults:

• The recommended dosage of Vemlidy is 25 mg (one tablet) taken orally once daily with food. Prior to initiation of Vemlidy, patients should be tested for HIV-1 infection. Vemlidy alone should not be used in patients with HIV infection. Please see drug label for dose modifications in patients with hepatic and renal impairment.

Pediatrics:

• The recommended dosage of Vemlidy is a 25 mg tablet once-daily

Mechanism of Action

Vemlidy (tenofovir alafenamide) is a phosphonamidate prodrug of tenofovir (2’-deoxyadenosine monophosphate analog). Tenofovir alafenamide as a lipophilic cell-permeant compound enters primary hepatocytes by passive diffusion and by the hepatic uptake transporters OATP1B1 and OATP1B3. Tenofovir alafenamide is then converted to tenofovir through hydrolysis primarily by carboxylesterase 1 (CES1) in primary hepatocytes. Intracellular tenofovir is subsequently phosphorylated by cellular kinases to the pharmacologically active metabolite tenofovir diphosphate. Tenofovir diphosphate inhibits HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain-termination. 

Side Effects

Adverse effects associated with the use of Vemlidy may include, but are not limited to, the following:

• headache
• abdominal pain
• fatigue
• cough
• nausea
• back pain

Vemlidy comes with the following Black Box Warning: 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 may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely in patients who discontinue Vemlidy. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

Clinical Trial Results

The FDA approval of Vemlidy for adults was based on two international phase 3 studies (studies 108 and 110) among 1,298 treatment-naïve and treatment-experienced adult patients with chronic HBV infection. Study 108 randomized and treated 425 HBeAg-negative patients with either Vemlidy or Viread (tenofovir disoproxil fumarate) and study 110 randomized and treated 873 HBeAg-positive patients with either Vemlidy or Viread. Both studies met their primary endpoint of non-inferiority to Viread based on the percentage of patients with chronic hepatitis B with plasma HBV DNA levels below 29 IU/mL at 48 weeks of therapy: 94 percent and 93 percent, respectively, for study 109, and 64 percent and 67 percent, respectively, for Study 110. In an integrated analysis of both studies, patients receiving Vemlidy demonstrated improvements in certain bone and renal laboratory parameters compared to those treated with Viread. Patients in the Vemlidy arm also experienced numerically higher rates of normalization of blood serum alanine aminotransferase (ALT) levels.

The FDA approval of Vemlidy for pediatrics was supported by 24-week data from a Phase 2 clinical trial (Trial 1092) comparing treatment with Vemlidy 25 mg to placebo among 70 treatment-naïve and treatment-experienced patients aged 12 to less than 18 years weighing at least 35 kg. The study met its primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy; overall, 21% (10/47) of subjects treated with Vemlidy 25 mg achieved HBV DNA <20 IU/mL at 24 weeks compared to 0% (0/23) of subjects treated with placebo.