A phase 3 study evaluating the histologic and virologic improvement of hepatitis B antigen positive (HBeAg) patients randomized to either lamivudine or entecavir demonstrated that patients treated with entecavir had a significantly higher rate of histologic, virologic, and biochemical improvement. Researchers also observed less viral resistance with entecavir.
A phase 3 study evaluating the histologic and virologic improvement of hepatitis B antigen positive (HBeAg) patients randomized to either lamivudine or entecavir demonstrated that patients treated with entecavir had a significantly higher rate of histologic, virologic, and biochemical improvement. Researchers also observed less viral resistance with entecavir.
Patients in the double-blind, double-dummy, multicenter, randomized controlled trial published in the New England Journal of Medicine (NEJM) received entecavir 0.5 mg once daily or lamivudine 100 mg once daily for a minimum of 52 weeks. Of 1,056 screened patients aged ≥16 years, 715 were assigned, and 709 patients received at least 1 dose of either entecavir (n=354) or lamivudine (n=355).
The primary end point was histologic improvement at Week 48 with necroinflammatory fibrosis scores also being evaluated. Secondary end points also measured in the 48th week were a reduction in hepatitis B virus (HBV) DNA level from baseline and patients with undetectable HBV DNA; decrease in fibrosis scores; HBeAg loss; HBeAg seroconversion; and alanine aminotransferase (ALT) normalization <1.25 times the upper limit of normal (ULN). Patients who responded at Week 48 were followed for an additional 24 weeks to evaluate sustained virologic response (SVR) and serologic benefit. A safety analysis also was performed (n=709). The primary safety end point was the number of patients who discontinued treatment because of an adverse effect. Resistance analysis also was performed. A 2-stage efficacy evaluation was planned, initially testing non-inferiority to lamivudine. If non-inferiority was established, a second test for superiority was conducted.
In the primary end point at Week 48, 72% of entecavir-treated patients had a higher rate of histologic improvement compared with 62% of the lamivudine group (difference estimate [DE]=9.9; 95% CI, 2.6–17.2; P=.009). Improved fibrosis also was noted in the entecavir-treated patients (39% vs 35%; P=.41). Worsening of fibrosis scores was noted in 8% of entecavir-treated patients compared with 10% of lamivudine-treated patients. The ALT normalized in more entecavir-treated patients (68%) compared with the lamivudine group (60%). HBV was undetectable at Week 48 in 67% of entecavir-treated patients versus 36% of lamivudine-treated patients (DE=30.3; 95% CI, 23.3–37.3; P<.001).
Mean reductions in viral load from baseline were greater and statistically significant in the entecavir-treated patients compared with the lamivudine-treated patients (DE=–1.52; 95% CI, –1.78 to –1.27; P<.001) HBeAg loss and seroconversion occurred in the same percentage of individuals in both groups.
A protocol-defined response at Week 48 was observed in 74 entecavir-treated patients (21%) and 67 lamivudine-treated patients (19%). Virologic response was attained in 247 entecavir-treated patients (70%) versus 165 lamivudine-treated patients (46%). Nineteen entecavir-treated patients (5%) did not respond to treatment compared with 94 lamivudine-treated patients (26%).
For the protocol-defined response, 82% of entecavir-treated patients and 73% of lamivudine-treated patients had an SVR at Week 24 following therapy discontinuation. During the first year of administration, 63 lamivudine-treated patients had virologic rebound compared with 6 entecavir-treated patients.
Adverse effects were similar between the 2 treatment groups (eg, headache, upper respiratory tract infection, nasopharyngitis, and cough). There were 2 deaths in the lamivudine-treated patients, which were believed to be unrelated to the study. Resistance to entecavir following longer treatment courses is not unknown.
SOURCE Chang T-T, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HbeAg-positive chronic hepatitis B. New Engl J Med. 2006;354:1001–1010.
David Calabrese of OptumRx Talks Top Three Drugs in Pipeline, Industry Trends in Q2
July 1st 2020In this week's episode of Tuning Into The C-Suite podcast, MHE's Briana Contreras chatted with David Calabrese, R.Ph, MHP, who is senior vice president and chief pharmacy officer of pharmacy care services company, OptumRx. David is also a member of Managed Healthcare Executives’ Editorial Advisory Board. During the discussion, he shared the OptumRx Quarter 2 Drug Pipeline Insights Report of 2020. Some of the information shared includes the three notable drugs currently being reviewed or those that have been recently approved by the FDA. Also discussed were any interesting industry trends to watch for.
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