Studies of Sustained Efficacy/Tolerability of LEXIVA After 96 Weeks of Treatment Presented at IAC
13 Julio 2004 - 8:01AM
PR Newswire (US)
Studies of Sustained Efficacy/Tolerability of LEXIVA After 96 Weeks
of Treatment Presented at IAC BANGKOK, Thailand, July 13
/PRNewswire-FirstCall/ -- The protease inhibitor (PI) LEXIVA(R)
(fosamprenavir calcium, formerly GW433908, or 908) in combination
with abacavir and lamivudine demonstrated sustained efficacy and
safety after long-term treatment (96 weeks), according to studies
of treatment results in therapy-naive patients, approximately 50
percent of whom had baseline CD4 cell counts less than 200
cells/mm3. APV30005 was a rollover trial for patients enrolled in
SOLO and NEAT, two Phase III clinical trials that were pivotal to
the October 2003 FDA approval of LEXIVA. The data were presented
here today at the International AIDS Conference (IAC). LEXIVA was
co-discovered by GlaxoSmithKline (GSK) and Vertex Pharmaceuticals
(NASDAQ: VRTX). This study reported results of long-term treatment
with LEXIVA dosed with ritonavir (LEXIVA/r) once a day (QD) in
patients from SOLO and outcomes from patients in NEAT, who took
LEXIVA without ritonavir twice a day (BID). LEXIVA was given in
combination with abacavir and lamivudine. In this analysis, viral
suppression and immunologic improvements were sustained through 96
weeks of treatment with LEXIVA and LEXIVA/r. At the time this
preliminary analysis was performed, approximately half the patients
(175 out of 322) had reached 96 weeks. This study is on-going.
LEXIVA and LEXIVA/r were well-tolerated, with less than or equal to
two percent of the patients discontinuing due to adverse events.
LEXIVA is indicated for the treatment of HIV infection in adults in
combination with other antiretroviral medications. The following
points should be considered when initiating therapy with
LEXIVA/ritonavir (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. "We are
encouraged by the preliminary analyses of 96-week data that suggest
the potency and safety demonstrated by LEXIVA at 48 weeks may be
sustained by long-term treatment in naive patients," said Doug
Manion, M.D., vice president of HIV Medicines Development Center at
GSK. LEXIVA/r QD (poster # 4507) A total of 210 patients (median
baseline viral load 4.82 log10 copies/mL and median CD4 cell count
of 168 cells/mm3) taking LEXIVA/r QD with abacavir and lamivudine
who completed SOLO subsequently enrolled in the follow-up study,
APV30005. Of these patients, 115 completed 96 weeks of therapy
before the deadline for data collection, and were included in the
interim analysis presented at IAC. Of 113 patients for whom lab
data were available, 109 (96 percent) had VL below 400 copies/mL
and 97 (86 percent) had VL below 50 copies/mL at 96 weeks. From
baseline to week 96, median CD4 cell counts increased from 168 to
461 cells/mm3 indicating continued immunologic improvement. No
selection of PI-resistant mutations was observed in any patients
with virologic failure over the 96 weeks. "In this analysis,
long-term treatment with LEXIVA/r QD resulted in sustained
virologic suppression, continued immunologic improvements and no
selection of PI-resistance up to 96 weeks," said Joseph C. Gathe,
Jr., M.D., F.A.C.P., clinical instructor, Department of Internal
Medicine, Baylor College of Medicine, Houston, Texas. The most
common moderate to severe drug-related adverse events over the
96-week study period with LEXIVA/r QD were diarrhea (9 percent of
patients) and nausea (7 percent), most of which occurred before
patients completed the 48-week SOLO trial. No new cases of diarrhea
and only one new case of drug- related nausea were reported in
APV30005. Of 19 patients (9 percent) who discontinued treatment
between 48 and 96 weeks, 4 (2 percent) discontinued due to an
adverse event. Fasting HDL cholesterol levels continued to increase
from baseline to week 96 (mean change of 12 mg/dL). Mean
triglyceride and total cholesterol values increased from baseline
to week 48, they remained stable from week 48 to week 96. LEXIVA
BID (poster # 4506) APV30005 enrolled 112 patients (median baseline
viral load of 4.82 log10 copies/mL and 216 CD4 cells/mm3) from the
NEAT trial who had completed 48 weeks of treatment with LEXIVA BID
with abacavir and lamivudine. A total of 60 patients completed 96
weeks. Fifty-four of the 60 (90 percent) had viral load (VL) below
400 copies/mL and 51 (85 percent) had VL below 50 copies/mL at 96
weeks. The median increase in CD4 cell counts was 205 cells/mm3 at
48 weeks, rising to a total median increase of 255 cells/mm3 over
96 weeks of treatment. Fasting HDL cholesterol levels continued to
increase from baseline to week 96 (mean change of 11 mg/dL), with
no significant increase in the TC/ HDL-C ratio. Although increases
were observed in mean triglyceride values during the study, the
mean values returned to baseline in those patients who had
completed 96 weeks of the study as of the data cut-off (or at the
time of data analyses). "Over a long-term course of treatment,
LEXIVA sustained its potency in suppressing HIV, was
well-tolerated, and no new safety concerns were observed over 96
weeks of treatment," said Jeffrey P. Nadler, M.D., University of
South Florida College of Medicine, Tampa, Fla. The most common
moderate to severe drug-related adverse events were diarrhea (8
percent), nausea (8 percent) and rash (5 percent). The
discontinuation rate was low (6 percent) and no patients
discontinued the regimen because of adverse events. Selection of
PI-associated resistance mutations was observed in five patients
with viral loads above 1000 copies/mL. Important Safety Information
about LEXIVA HIV medicines do not cure HIV infection/AIDS or
prevent passing HIV to others. 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. Treatment with LEXIVA and ritonavir has resulted
in the increase in concentration of triglycerides. The most common
adverse events seen in clinical trials with LEXIVA were diarrhea,
nausea, vomiting, headache and rash. About GlaxoSmithKline
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.
About Vertex Vertex Pharmaceuticals Incorporated is a global
biotechnology company committed to the discovery and development of
breakthrough small molecule drugs for serious diseases. The
Company's strategy is to commercialize its products both
independently and in collaboration with major pharmaceutical
partners. Vertex's product pipeline is principally focused on viral
diseases, inflammation, autoimmune diseases and cancer. Vertex
co-promotes the HIV protease inhibitor Lexiva(R) with
GlaxoSmithKline. Vertex Safe Harbor Statement This press release
may contain forward-looking statements. While management makes its
best efforts to be accurate in making forward-looking statements,
such statements are subject to risks and uncertainties that could
cause Vertex's actual results to vary materially. These risks and
uncertainties include those risks listed under Risk Factors in
Vertex's form 10-K filed with the Securities and Exchange
Commission on March 15, 2004. Lexiva(R) is a registered trademark
of the GlaxoSmithKline group of companies. Vertex's press releases
are available at http://www.vrtx.com/. Vertex Contacts: Michael
Partridge, Director, Corporate Communications, (617) 444-6108 Jaren
Irene Madden, Manager, Media Relations, (617) 444-6750
GlaxoSmithKline Contact: Mary Faye Dark, 919/483-2839 (media)
DATASOURCE: Vertex Pharmaceuticals Incorporated CONTACT: Michael
Partridge, Director, Corporate Communications, +1-617-444-6108, or
Jaren Irene Madden, Manager, Media Relations, +1-617-444-6750, both
of Vertex; or Mary Faye Dark of GlaxoSmithKline, +1-919-483-2839
Web site: http://www.vrtx.com/ Company News On-Call:
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