BANGKOK, July 12 /PRNewswire-FirstCall/ -- HIV treatment regimens
containing the protease inhibitor (PI) LEXIVA(R) (fosamprenavir calcium) dosed
with ritonavir (LEXIVA/r) or lopinavir (LPV) and ritonavir (LPV/r) were
effective in suppressing HIV in patients who had failed prior PI-containing
regimens, according to information presented here today at the International
AIDS Conference (IAC). Lexiva was co-discovered by GlaxoSmithKline (GSK) and
Vertex Pharmaceuticals (Nasdaq: VRTX).
The data are based on 48-week results of the CONTEXT study, a Phase III
clinical trial that enrolled patients who had experienced virologic failure
(VF) while receiving one to two prior PI regimens. Patients were randomized
to take one 700mg LEXIVA tablet and one 100mg capsule of ritonavir (LEXIVA/r)
twice a day (BID) (four capsules daily), 1400mg Lexiva plus 200mg ritonavir
once a day (QD), or three LPV/r capsules, each combining 400mg LPV and 100mg
of ritonavir BID (six capsules daily). PIs were taken in combination with two
nucleoside reverse transcriptase inhibitors (NRTIs).
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/r in PI-experienced
patients: the PI-experienced patient study was not large enough to reach a
definitive conclusion that LEXIVA/r and LPV/r are clinically equivalent.
Once-daily administration of LEXIVA dosed with ritonavir is not
recommended for PI-experienced patients, who are advised to take one 700mg
tablet of LEXIVA BID in combination with one 100mg capsule of ritonavir BID.
At 48-weeks, 58 percent (62 of 107 patients) taking LEXIVA/r BID achieved
viral loads (VL) below 400 copies/mL, and 46 percent (49) had VL below 50
copies/mL. Of 103 patients who took LPV/r BID, 61 percent (63) achieved VL
below 400 copies/mL and 50 percent (52) had VL below 50 copies/mL.
At baseline, patients in both treatment arms had similar viral loads, CD4
cell counts, and PI-associated resistance mutations. Prior NRTI experience
and the presence of RT-associated mutations, however, were higher at baseline
in patients who subsequently were randomized to the study arm that included
LEXIVA/r compared to the group assigned to the study arm containing LPV/r.
There was a higher incidence of NRTI mutations in the LEXIVA/r BID group (mean
1.7) compared to the group taking LPV/r BID (1.4). This was primarily due to
a higher number of subjects harboring virus with three or more thymidine
analogue mutations (TAMS) in the LEXIVA/r BID group (38 percent), compared to
24 percent in the group taking LPV/r BID.
"There was no difference between the LEXIVA/r BID and lopinavir/r BID
study arms in the proportion of patients with virologic failure with 29
percent versus 27 percent respectively," said Edwin DeJesus, M.D., Infectious
Disease Consultants, Altamonte Springs, FL.
Mutations Present at Baseline
The most common protease-associated resistance mutations seen at baseline
among the 210 patients included in the study were:
* L90M in 63 patients (30 percent)
* M46I/L in 48 patients (23 percent)
* D30N in 45 patients (21 percent)
"There was no significant difference between the two study arms in the
virologic responses of patients who had these mutations present at baseline,"
said Rob Elston, GSK scientist and study presenter.
Viral suppression in the presence of L90M was achieved in 16 of 31
patients (52 percent) taking LEXIVA/r, and in 17 of 28 patients (61 percent)
taking LPV/r. Among patients with M46I/L mutations, 11 of 22 (50 percent)
taking LEXIVA/r and 12 of 24 (50 percent) taking LPV/r responded to treatment,
while 21 of 22 patients (95 percent) with D30N mutations responded in the arm
containing LEXIVA/r compared to 17 of 18 (94 percent) in the arm containing
Varying degrees of cross-resistance among HIV-1 protease inhibitors have
been observed. Because the potential for HIV cross-resistance among protease
inhibitors has not been fully explored, it is unknown what effect therapy with
LEXIVA will have on the activity of subsequently administered protease
inhibitors. Clinical relevance of resistance data is currently being
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
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.
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.
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 is a registered trademark of the GlaxoSmithKline group of
Vertex's press releases are available at http://www.vrtx.com.
Michael Partridge, Director, Corporate Communications, (617) 444-6108
Jaren Irene Madden, Manager, Media Relations, (617) 444-6750
Mary Faye Dark, 919/483-2839 (media)
SOURCE Vertex Pharmaceuticals
Web Site: http://www.vrtx.com