Adefovir reduces fibrosis in precore mutant HBV

liver411

InfoTrac Web: InfoTrac OneFile.

                                                                              
   Source:  Internal Medicine News, Feb 15, 2002 v35 i4 p27(1).
                                                                              
    Title:  Adefovir reduces fibrosis in precore mutant HBV. (Strain Does Not
            Produce E Antigen).(hepatitis B virus )
   Author:  Elizabeth Mechcatie
                                                                              
Subjects:  Hepatitis B - Drug therapy
            Antiviral agents - Evaluation
            Pharmaceutical industry - Products
Companies:  Gilead Sciences Inc. - Products
Locations:  United States
                                                                              
Electronic Collection:  A83679448
                   RN:  A83679448
                                                                              

Full Text COPYRIGHT 2002 International Medical News Group

Treatment with adefovir dipivoxil, an oral antiviral taken once a day, was
associated with significant improvements in liver histology in a 48-week study of patients with precore mutant chronic hepatitis B virus infections.

In the multinational study of patients with this hepatitis B virus (HBV)
strain, which does not produce the e antigen because of a mutation in the
viral genome, 64% of the 123 patients who received 10 mg of adefovir once a
day had improvements in liver histology after 48 weeks. Comparable
improvements were seen in 33% of the 62 patients on placebo, a significant difference.

The study, sponsored by manufacturer Gilead Sciences, is being continued for another 48 weeks to evaluate long-term safety and resistance profiles in the patients.

The significant improvements in liver histology were defined by at least a
2-point decline in the Knodell necro-inflammatory score and no concurrent
worsening in the fibrosis score, said Dr. Carol Brosgart, vice president of
clinical research at Gilead, Foster City, Calif.

The same degree of improvements in liver histology after 48 weeks was also seen in another pivotal multicenter, international trial comparing adefovir with placebo in 700 e antigen-positive patients with chronic HBV infections.

The company reported the results of this study in June.

Adefovir interferes with HBV polymerase, the enzyme necessary for HBV
replication. Gilead plans to file soon with the Food and Drug Administration
for approval of adefovir for the treatment of chronic HBV infection.

Secondary end points that were met in both studies at 48 weeks include
reductions in HBV viral load and serum ALT levels that were significantly
greater among those on adefovir, compared with those on placebo.

In the second study of e antigen-negative patients, 72% of those treated with adefovir and 29% of those on placebo had normalization of ALT levels,
according to a Gilead press release.

In both studies, the safety profile was similar to placebo over 1 year of
treatment.

No mutations resistant to adefovir were seen through 48 weeks, according to
Dr. Brosgart, who heads the hepatitis B clinical development program for
adefovir. She noted that resistant virus has not been seen in patients treated for more than 2 years.

The study of patients with precore mutant HBV was conducted in Southeast Asia, Greece, Australia, Canada, France, Israel, and Italy.

There were no sites in the United States, where at least 5% of people with
chronic hepatitis B have this mutation and do not express the e antigen,
despite active disease. The true prevalence of these infections may be higher, Dr. Brosgart said in an interview.

Adefovir has been available on a compassionate use basis for posttransplant
patients and patients waiting for liver transplants who have HBV infections
resistant to lamivudine (Epivir-HBV), which is an approved therapy for HBV
infections.

The nearly 300 patients treated in this program include those who no longer need transplants or repeat transplants and have been taken off the waiting lists, she noted.

There is no evidence that the drug works for hepatitis C, according to Dr.
Brosgart.

Gilead is beginning a pediatric development program for adefovir and is
working on a formulation that could be taken by children.
                                                                              
                                -- End --