RESEARCH TRIANGLE PARK, N.C., July 8 /PRNewswire/ -- The protease
inhibitor (PI) LEXIVA(R) (fosamprenavir calcium) dosed with ritonavir
(LEXIVA/r) once-daily (QD) as part of a first-line ART regimen provided
antiviral suppression that was comparable in this single study to the PI
nelfinavir (NFV) dosed twice-daily (BID), according to 48-week data from the
SOLO trial published in the July 23 issue of AIDS. Both regimens were
generally well-tolerated, according to the study's authors. LEXIVA (formerly
GW433908, or 908), the first PI to combine flexible dosing (QD or BID) in
PI-naive patients with no food or water restrictions, was approved by the U.S.
Food and Drug Administration in October 2003. Co-discovered by
GlaxoSmithKline (GSK) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX),
LEXIVA is indicated in combination with other antiretroviral agents for the
treatment of HIV infection in adults.
The following points should be considered when initiating therapy with
LEXIVA/r in PI-experienced patients: the PI-experienced patient study was not
large enough to reach a definitive conclusion that LEXIVA/r and
lopinavir/ritonavir are clinically equivalent. Once-daily administration of
LEXIVA plus ritonavir is not recommended for PI-experienced patients.
SOLO, an international open-label, multi-center study, evaluated the
safety and efficacy of LEXIVA/r QD versus NFV BID, in 649 therapy-naive
patients with HIV infection. Patients were randomized to take either two
700mg LEXIVA tablets plus two 100mg ritonavir capsules QD (4 pills daily) with
no food or water restrictions, or five 250mg nelfinavir tablets BID (10 pills
daily) with a meal. All patients also received the nucleoside reverse
transcriptase inhibitors abacavir (ABC) and lamivudine (3TC) BID.
"In clinical trials, LEXIVA has been shown to be an effective and well-
tolerated PI. LEXIVA also offers flexible dosing regimens, with a low pill
burden and options for once- or twice-daily dosing in PI-naive patients.
LEXIVA underscores GSK's commitment to provide state-of-the-art antiretroviral
therapies for patients," said Doug Manion, M.D., vice president for HIV
Clinical Research for the Infectious Diseases Medicines Development Center
(MDC) for GSK.
In the analysis of data from the SOLO trial reported in AIDS, 69 percent
of patients taking LEXIVA/r QD and 68 percent taking NFV BID had viral levels
below 400 copies/mL at 48 weeks. Other findings from the 48-week analysis:
-- 55 percent of patients taking LEXIVA/r QD and 53 percent taking NFV BID
achieved viral loads less than 50 copies/mL.
-- Virologic failure occurred in more patients taking NFV BID (17 percent)
than in patients taking LEXIVA/r QD (7 percent), but there were more
non-virologic failures with LEXIVA/r than with NFV (24 percent versus
-- Median CD4+ count increase from baseline to week 48 was 203 cells/mm3
in the group taking LEXIVA/r QD and 207 cells/mm3 in the NFV BID group.
-- Both regimens were well-tolerated. Moderate to severe drug-related
diarrhea was more common in patients taking NFV BID than those taking
LEXIVA/r QD (16 percent versus 9 percent; p=0.008).
-- Fasting lipid profiles were similar in both treatment arms.
SOLO enrolled 649 therapy-naive ethnic- and gender-diverse patients with
HIV (median viral RNA levels were 4.8 log10 copies/mL; median CD4+ counts
170/mm3). Twenty percent of patients entered the SOLO trial with CD4+ cell
counts below 50 cells/mm3 and 22 percent had a history of CDC Class C events,
(i.e., patient had experienced an opportunistic infection). Baseline
characteristics were similar between the two groups.
Clinical Trials with LEXIVA
More than 1,200 people -- both ART-naive and PI-experienced patients --
participated in three Phase III multicenter trials, including SOLO, to test
the safety and efficacy of LEXIVA with and without ritonavir. In all three
trials, study drugs were taken as part of combination therapy that included
LEXIVA is approved for dosing in therapy-naive patients in one of three
ways: 1) two 700mg tablets BID; 2) two 700mg tablets in combination with two
100mg ritonavir capsules QD; or 3) one 700mg tablet in combination with one
100mg ritonavir capsule BID. For PI-experienced patients, the recommended
dose is one 700mg tablet BID in combination with one 100mg capsule of
Important Safety Information about LEXIVA
HIV medicines do not cure HIV infection/AIDS or prevent passing HIV to
LEXIVA is contraindicated in patients with previously demonstrated
clinically significant hypersensitivity to any of the components of this
product or to amprenavir. Hyperglycemia, new onset or exacerbations of
diabetes mellitus, and spontaneous bleeding in hemophiliacs have been reported
with protease inhibitors. Redistribution/accumulation of body fat including
central obesity, dorsocervical fat enlargement (buffalo hump), peripheral
wasting, facial wasting, breast enlargement, and "cushingoid appearance" have
been observed in patients receiving antiretroviral therapy. The causal
relationship, mechanism, and long-term consequences of these events are
currently unknown. LEXIVA is contraindicated with ergot derivatives,
cisapride, pimozide, midazolam, and triazolam. If LEXIVA is coadministered
with ritonavir, flecainide and propafenone are also contraindicated. The most
common adverse events seen in clinical trials with LEXIVA were diarrhea,
nausea, vomiting, headache and rash.
GlaxoSmithKline is one of the world's leading research-based
pharmaceutical and healthcare companies and an industry leader in HIV research
and therapies. The company is engaged in basic research programs designed to
investigate new targets to treat HIV.
For full prescribing information for LEXIVA, please visit
AT A GLANCE
At 48 weeks:
-- Once daily (QD) dosing of the PI LEXIVA in combination with ritonavir
was comparable in this single study in efficacy as twice daily (BID)
dosing of nelfinavir (NFV) in PI-naive patients.
-- Patients took either LEXIVA/ritonavir, as 4 pills once daily with no
food or water restrictions, or 5 NFV tablets BID (10 pills daily) with
-- Virologic failure was seen in 7 percent of patients taking
LEXIVA/ritonavir and 17 percent of patients taking NFV.
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