STUDY HIGHLIGHTS POTENTIAL FOR MORE CONVENIENT ONCE-A-DAY ADMINISTRATION
Studies continue to support the effectiveness, durability, and ease-of-use of FORTOVASE®
(saquinavir). FORTOVASE is an enhanced formulation of INVIRASE® (saquinavir
mesylate). New data on FORTOVASE were presented at the 39th Interscience
Conference on Antimicrobial Agents and Chemotherapy in San Francisco.
Data from a study in uninfected volunteers demonstrated that FORTOVASE plus ritonavir
in a new once-a-day (or QD) regimen resulted in trough blood levels that were roughly five
times higher than those achieved in the study arm using FORTOVASE 1200-mg dosed three
times a day, its current standard dose. The trough blood level is the concentration of the
drug in patients blood immediately before the next dose of drug is taken and is
believed to be important in maintaining suppression of the virus.
Additional data supporting FORTOVASE twice-a-day (or BID) dosing and FORTOVASE use in
pediatric populations was also reported at the conference.
Data presented by Michael Saag, M.D.1 from a pharmacokinetic study evaluated
five different regimens of either FORTOVASE alone or FORTOVASE plus ritonavir in 41
healthy volunteers. Volunteers were enrolled in five arms: four arms explored FORTOVASE
once daily (QD) + ritonavir QD at various doses, while the fifth arm examined FORTOVASE
alone three times daily (TID).
Pharmacokinetic parameters (geometric mean) of saquinavir were summarized:
The study showed that FORTOVASE 1600-mg QD + ritonavir
100-mg QD provided substantially higher levels of drug (as demonstrated by Cmax
and AUC24h; see table) in the blood than the other combinations in the
study over a 24-hour period, as well as the current standard dose of FORTOVASE 1200-mg
TID. The FORTOVASE 1600-mg QD + ritonavir 100-mg QD regimen was generally well-tolerated
over the course of the pharmacokinetic study. Studies of this combination in people with
HIV are ongoing.
The TIDBID Study (M61018)
In addition to preliminary data on once-daily FORTOVASE dosing, the body of data on
twice-daily FORTOVASE dosing continues to grow2. In a large, prospective,
intent-to-treat 24-week analysis (with a treatment extension to 48 weeks) presented here,
838 patients were studied in three groups: those receiving FORTOVASE 1600-mg BID + 2 NAs,
FORTOVASE 1200-mg BID + VIRACEPT® (nelfinavir mesylate) 1250-mg BID + 1 NA or
FORTOVASE 1200-mg TID + 2 nucleoside analogues (NAs).
Complete cohort data at week 24 are summarized in the table below:
The TIDBID study continues to demonstrate that FORTOVASE
taken twice-a-day + 2 NAs suppresses viral load similarly to its current standard dose,
FORTOVASE taken three times a day + 2 NAs. In addition, the FORTOVASE BID regimen supports
the sustained increase in CD4 cells as seen in other FORTOVASE trials. The TIDBID data
also demonstrate that all three regimens were well-tolerated.
FORTOVASE Well-Tolerated and Effective In Children
Mark Kline, M.D.3, reported on a two-part study in children using FORTOVASE.
In part one, fourteen children (median age 7 years) were enrolled to receive FORTOVASE 50
mg/kg TID + 2 NRTIs for 72 weeks. For those children unable to reach the FORTOVASE
pharmacokinetic target in part one, NFV was added to their regimens. At week 72 (end of
part one), 43% had viral loads < 400 copies/ml and 36% were at < 50 copies/ml with
an average increase of 365 CD4 cells/mm3 over baseline.
Thirteen children (median age 4 years) were enrolled in part two and received FORTOVASE
33 mg/kg TID + NFV 30 mg/kg TID + 1-2 NRTIs for 48 weeks. At week 48, 69% had viral loads
< 400 copies/ml and 62% were at < 50 copies/ml with a mean CD4 cell increase of 104
cells/mm3 over baseline. These two regimens demonstrate FTV's safety and
efficacy in children.
Favorable FORTOVASE Profile Shown In Comparative Data on Metabolic Markers
Many researchers believe that triglyceride and cholesterol elevations and other lipid
abnormalities may be early indicators of problems like lipodystrophy (the redistribution
of body fat associated with some anti-HIV medications), and premature cardiovascular
disease. The following study looked at the degree to which FORTOVASE may impact
triglycerides and other markers to help physicians and patients make informed decisions
regarding treatment options.
Dr. A. Wensing4 presented data from a small (n = 17) prospective study that
examined the metabolic and virologic effects of switching from a ritonavir-containing
combination regimen to one containing either FORTOVASE + VIRACEPT® (nelfinavir
mesylate; NFV) or NFV with no change in the underlying nucleoside analogues (NAs) on
patients whose virus was suppressed. This study was intended to provide an option for
patients on ritonavir-based regimens during the 1998 Abbott/ritonavir manufacturing crisis
and subsequent ritonavir-capsule formulation withdrawal.
At week 24, viral load remained undetectable and CD4 counts remained stable in both
arms of the study. In addition, mean triglyceride levels decreased from 4.42 to 2.62
mmol/l (p = 0.001) in both arms. GGT levels also declined from a mean of 178.17 units/l at
baseline to 102.58 units/l (p = 0.015)5.
Insight into Predictors of Patient Response with FORTOVASE
Michael Hughes, M.D.6 reported data from a retrospective meta-analysis that
reviewed data from several FORTOVASE clinical trials with data out through 48 weeks (n =
648), looking to identify predictors for both time to first viral load suppression below
400 copies/ml and time from suppression to first rebound. Patients with higher CD4 counts,
no history of anti-HIV therapy, or who were older were more likely to achieve suppression
after adjusting for pre-treatment RNA levels. Higher pre-treatment CD4 counts were
significantly associated with longer duration of suppression.
FORTOVASE Pharmacokinetic Synergy with Ritonavir, Co-administration with Other
Drugs More Clearly Defined
Karin Jorga, Ph.D.7 presented data from a retrospective review of
pharmacokinetic data for FORTOVASE co-administered with other agents in both healthy and
HIV-positive adults. FORTOVASE in the plasma was reduced by efavirenz, rifabutin, and
rifampin, but increased 2 to 5 times by indinavir, nelfinavir, clarithromycin, and
ketoconazole, and up to 20 times by ritonavir. The contraindication of FTV with
terfenadine was reinforced.
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