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 39^th 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.

FORTOVASE Once-a-Day

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).

The study showed that FORTOVASE 1600-mg QD + ritonavir 100-mg QD provided substantially higher levels of drug (as demonstrated by C_max and AUC_24h; 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).

* N=838 intent-to-treat

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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