EXPERT ANALYSIS FROM DIGESTIVE DISEASES: NEW ADVANCES

PHILADELPHIA (FRONTLINE MEDICAL NEWS) – Tenofovir alafenamide, the newest kid on the block for treatment of chronic hepatitis B, not only has less bone and renal effects than tenofovir disoproxil, but now also appears to improve those parameters in patients switched over from the older tenofovir formulation, according to Paul Kwo, MD.

“Renal function, as well as hip and spine bone mineral density measurements, all improve after you flip,” said Dr. Kwo, director of hepatology at Stanford (Calif.) University.

Dr. Kwo described some of the latest data on the newer tenofovir formulation in a hepatitis B update he gave at the conference, jointly provided by Rutgers and Global Academy for Medical Education.

Tenofovir alafenamide, a nucleoside analogue reverse transcriptase inhibitor, was approved in November 2016 for treatment of adults with chronic hepatitis B virus (HBV) infection and compensated liver disease.

It has similar efficacy to tenofovir disoproxil, with fewer bone and renal effects, according to results of two large international phase 3 trials.

Some of the latest data , presented in October 2017 at The Liver Meeting in Washington, show that switching patients from tenofovir disoproxil to tenofovir alafenamide improved creatinine clearance and increased rates of alanine aminotransferase normalization, with sustained rates of virologic control, over 48 weeks of treatment.

Similar results were seen for bone mineral density. “It goes up over time, and you approach bone mineral density levels that are similar to [levels in] those who are on tenofovir alafenamide long term,” Dr. Kwo said, commenting on results of the study.

Compared with tenofovir disoproxil, tenofovir alafenamide is a slightly different prodrug of tenofovir, according to Dr. Kwo.

The approved dose of tenofovir alafenamide is 25 mg, compared with 300 mg for tenofovir disoproxil. “It’s more stable in the serum, so you don’t need higher levels, and you have fewer off-target effects,” Dr. Kwo said.

The two agents are “Coke and Pepsi” in terms of efficacy, he added, noting that comparative studies showed similar efficacy on endpoints of percentage HBV DNA less than 29 IU/mL and log10 HBV DNA change.

Very low rates of resistance are seen with first-line therapies for chronic hepatitis B, including entecavir and tenofovir disoproxil. “We wouldn’t expect (tenofovir alafenamide) to be any different, but nonetheless the surveillance has to happen,” Dr. Kwo said.

Tenofovir alafenamide is not yet listed in the official recommendations of the American Association for the Study of Liver Diseases, but it is in current guidelines from the European Association for the Study of the Liver.

The published EASL guidelines provide guidance on how tenofovir alafenamide fits into the treatment armamentarium for HBV.

Going by the EASL recommendations, age greater than 60 years, bone disease, and renal alterations are all good reasons to use tenofovir alafenamide as first-line therapy for hepatitis B, according to Dr. Kwo.

Dr. Kwo reported disclosures related to AbbVie, Allergan, Bristol-Myers Squibb, Conatus Pharmaceuticals, Dova Pharmaceuticals, DURECT, Gilead Sciences, Merck, and Shionogi.

Global Academy and this news organization are owned by the same company.

imnews@frontlinemedcom.com

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