®
FORTOVASE® (saquinavir):
Clinical Studies Highlight New Formulation's Power and ConvenienceStudies continue
to support the effectiveness, durability, and ease-of-use of FORTOVASE®
(saquinavir). FORTOVASE is an enhanced formulation of INVIRASE® (saquinavir
mesylate). The most recent data on FORTOVASE were presented at the 6th
Conference on Retroviruses and Opportunistic Infections in Chicago; they demonstrated both
the potency and the durability of FORTOVASEs anti-HIV effect in combination
regimens. These data were again presented in Geneva during the European Launch Symposium
for FORTOVASE on May 8, 1999.
FORTOVASE: Consistent, Powerful Outcome
Dr. Ronald Mitsuyasu of the University of California at Los Angeles School of Medicine
recently presented several summaries of FORTOVASE trials that demonstrate a remarkable
consistency of potent virologic suppression over time. More importantly, the powerful
antiviral effect of FORTOVASE is durable out to at least 72 weeks as shown by the NV 15355
study.
Summary of FORTOVASE Activity
Studies
FORTOVASE + 2 nRTIs1 (24 weeks) |
Study |
Proportion of patients
<400 copies/ml (%) |
|
On-treatment |
Intent-to-treat |
Naïve patients |
|
|
NV15355 |
80 |
63 |
NV15355 (72 wk) |
80 |
50 |
SUN |
82 |
55 |
CHEESE |
90 |
832 |
Mikado |
76 |
63 |
NA-experienced patients |
|
|
SPICE3 |
64 |
54 |
TIDBID (tid)3,4 |
74 |
64 |
TIDBID (bid)3,4 |
69 |
58 |
1 FORTOVASE used
according to current guidelines (initiated in combination with 2 nRTIs at least one of
which is new). 2 Using last observation carried forward. 3
Population included antiretroviral-experienced patients. 4 Interim
results (242 patients). |
Summary of FORTOVASE Activity
Studies
FORTOVASE + 2 nRTIs1 |
Study |
Mean CD4 count increase
(cells/mm3) |
|
24 weeks |
48 weeks |
72 weeks |
Naïve patients |
|
|
|
NV15355 |
92 |
169 |
225 |
SUN |
163 |
265 |
NA |
CHEESE |
162 |
NA |
NA |
Mikado2 |
106 |
NA |
NA |
NA-experienced patients |
|
|
|
SPICE3 |
84 |
124 |
215 |
TIDBID (tid)3,4 |
153 |
NA |
NA |
TIDBID (bid)3,4 |
147 |
NA |
NA |
1 FORTOVASE used
according to current guidelines (initiated in combination with 2 nRTIs at least one of
which is new). 2 Median value. 3 Population included
antiretroviral-experienced patients. 4 Interim results (242 patients).
NA data not available |
The TIDBID Study (M61018)
Data have been presented showing the continued effectiveness of twice-daily dosing of
FORTOVASE as part of a triple combination regimen. This 48-week randomized, open-label,
multicenter study compared FORTOVASE 1200 mg TID + 2 new nucleoside analogs (NAs) to
either FORTOVASE 1600 mg BID + 2 new NAs or FORTOVASE 1200 mg BID + VIRACEPT 1250 mg BID +
1 new NA. Subjects were antiretroviral-naïve or NA-experienced (but naïve to at least
one NA) with HIV-RNA level >5,000 (3.7 log10) and no CD4
restrictions. The study includes an option to intensify treatment at week 16.
The results at week 32 show the following:
Group |
N |
% of subjects
<400 copies/ml
(OT/ITT) |
% of subjects
<50 copies/ml
(OT/ITT) |
Mean change from baseline
to week 32 |
|
|
|
|
HIV-RNA log10 |
CD4 cells/mm3 |
FTV TID + 2 NAs |
168 |
79/54 |
61/41 |
-2.5 |
+160 |
FTV BID + 2 NAs |
166 |
71/49 |
57/40 |
-2.4 |
+148 |
FTV BID +
NFV BID + 1 NA |
160 |
74/45 |
60/36 |
-2.4 |
+178 |
These preliminary data support the potency of twice-daily
administration of FORTOVASE. Providing twice-daily regimens will make it easier for people
infected with HIV to adhere to their treatment regimens by making these regimens more
convenient while retaining the dramatic survival benefits of protease inhibitors.
The NV 15355 Study
One of the driving forces behind the novel data analyses being undertaken by Roche and
the clinical investigators involved in the FORTOVASE studies is to provide information
which will allow physicians to further improve upon the results being achieved with
FORTOVASE. In the case of NV 15355, Roche and the clinical investigator team have
identified predictive indicators of potential treatment success or failure. These
indicators can guide physicians and patients in making informed decisions designed
to achieve maximum treatment success.
NV 15355 is an open-label study designed to compare the effects on viral load of the
hard-gel capsule formulation of saquinavir (INVIRASE) -- to the enhanced soft-gel capsule
formulation of saquinavir (FORTOVASE) -- in the antiretroviral-naïve individuals (viral
load >5,000 (4.40 log10) copies/ml) when used in combination with two
nucleoside reverse transcriptase inhibitors (nRTIs).
Dr. C Tsoukas of Montreal General Hospital, Montreal, has presented data showing that
using on treatment analysis, 80% of subjects taking FORTOVASE were <400 copies/ml and
75% were <50 copies/ml at week 72. Using the most stringent analysis (ITT with missing
values equals failure),1 50% of subjects taking FORTOVASE subjects maintained
<400 copies/ml and 47% maintained <50 copies/ml at week 72. These data again
highlight the durability of FORTOVASE-containing combination regimens.
NV 15355 is one of the first studies to actually provide this insight into the
predictive value of crossing the 400/ml and 50 copies/ml levels of viral suppression.
Specifically, subjects who did not reach <400 copies/ml at week 12 were at risk of
virologic failure by week 72. Week 12 seems to be too soon to predict virology failure at
week 72 for those who did not reach <50 copies/ml, however inability to reach <50
copies/ml at week 24 was predictive of virologic failure at week 72.
These data reveal that close viral load monitoring, especially through week 24, can
serve as a prognostic indicator of likelihood of success or failure of a regimen of
FORTOVASE plus 2 NAs. With this insight, physicians can then choose which course of action
treatment intensification or switching medications is most likely to succeed
for the patient.
Time and level of suppression |
Percentage suppressed on FTV (OT/ITT) |
£ 400 at
week 12 and £ 50 at week 72 |
85%/63% |
³ 400 at
week 12 and £ 50 at week 72 |
22%/10% |
£ 50 at
week 12 and £ 50 at week 72 |
95%/69% |
³ 50 at
week 12 and £ 50 at week 72 |
61%/34% |
£
50 at week 24 and £ 50 at week 72 |
94%/79% |
³ 50 at
week 24 and £ 50 at week 72 |
17%/8% |
Roche currently offers one of the broadest portfolios of
HIV therapies and diagnostics and provides the entire spectrum of HIV care, from treatment
to diagnostics to research for the future. The Roche Group is a research-based health care
company with principal businesses in pharmaceuticals, diagnostics, vitamins, and
fragrances and flavours. Roche discovers, develops, and markets prescription drugs in key
therapeutic areas such as virology, infectious diseases, cardiology, oncology,
transplantation, and obesity to provide diagnostic tests and treatments for currently
unmet medical needs.
1The ITT MV=F
(Missing Value = Failure) analysis excludes the eight patients who switched from FORTOVASE
to Invirase. |