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FORTOVASE (saquinavir): Clinical Studies Highlight New Formulation's Power and Convenience

Studies 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 FORTOVASE’s 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
Nave 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
Nave 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-nave or NA-experienced (but nave 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-nave 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%
400 at week 12 and 50 at week 72 22%/10%
50 at week 12 and 50 at week 72 95%/69%
50 at week 12 and 50 at week 72 61%/34%
  50 at week 24 and 50 at week 72 94%/79%
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.


 
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