New Tenofovir Formulation Provides Safer Hepatitis B Treatment

By Will Boggs MD

September 30, 2016

NEW YORK (Reuters Health) - A new prodrug formulation, tenofovir alafenamide, effectively treats chronic hepatitis B virus (HBV) infection with fewer bone and renal adverse effects than tenofovir disoproxil fumarate, according to two noninferiority trials.

Tenofovir disoproxil fumarate has potent antiviral activity in patients with chronic HBV infection, but long-term use has been associated with renal toxic effects and reduced bone mineral density (BMD) in some patients.

In the first study, Dr. Henry L. Y. Chan from The Chinese University of Hong Kong and colleagues from 161 centers in 19 countries compared the two formulations in 873 patients with HBeAg-positive chronic HBV infection.

In the second study, Dr. Maria Buti from Hospital Universitari Vall d'Hebron in Barcelona, Spain, and colleagues from 105 centers in 17 countries made a similar comparison in 426 patients with HBeAg-negative chronic HBV infection.

The studies were published online September 22 in The Lancet Gastroenterology & Hepatology.

Both showed that treatment with tenofovir alafenamide met the primary endpoint of noninferiority to tenofovir disoproxil fumarate with respect to the proportion of patients with HBV DNA less than 29 IU/mL at week 48 of treatment.

Among HBeAg-positive patients, BMD decreases at the hip and spine were significantly smaller with tenofovir alafenamide treatment, and patients treated with tenofovir alafenamide had significantly smaller increases in serum creatinine (although the increases were small in both groups).

Results were similar among HBeAg-negative patients.

Both formulations of tenofovir were well-tolerated, and most adverse events were mild to moderate in severity.

The authors of both studies anticipate further long-term follow-up to ascertain whether these outcomes are durable and translate into reduced incidences of bone and renal events.

"Further research and long-term and real-world clinical data are needed to be able to definitively conclude whether tenofovir alafenamide is safer than tenofovir disoproxil fumarate," writes Dr. Willem P. Brouwer from Erasmus University Medical Center Rotterdam, the Netherlands, in a related commentary. "For now, these results for tenofovir alafenamide are very exciting, but might be more of an evolution than a revolution."

Dr. Yao-Chun Hsu from China Medical University in Taichung City, Taiwan, who recently compared the effectiveness of nucleoside/nucleotide analogs in chronic HBV patients undergoing chemotherapy, told Reuters Health by email, "From this trial, we probably can argue that tenofovir alafenamide (TAF) is as efficacious as tenofovir disoproxil fumarate (TDF), at least for 48-week use. TAF potentially can replace TDF as the first-line regimen in the general chronic hepatitis B patients."

"Judging from the superior results of TAF in BMD and renal function, I'd believe that the new agent is particularly preferred in the elderly, postmenopausal women, patients with chronic kidney disease, or those vulnerable to renal injury," added Dr. Hsu, who was not involved in the new work.

But there are some limitations, he said, such as the relatively short trial length and the enrollment of mostly Asian patients.

"Moreover," Dr. Hsu added, "those with advanced liver disease (decompensated status or hepatocellular carcinoma) were not included. All these caveats should be kept in mind when interpreting the results."

Gilead Sciences funded both studies and employed several of the authors.

Dr. Chan and Dr. Buti did not respond to requests for comments.


Lancet Gastroenterol Hepatol 2016.