lexiva
Generic Name: fosamprenavir calcium
Date of Approval: October 20, 2003
Manufacturer: GlaxoSmithKline
Treatment for: HIV infection
The U.S lexiva. Food and Drug Administration (FDA) has granted marketing clearancefor Lexiva (fosamprenavir calcium), a new protease inhibitor (PI) for the treatmentof HIV infection in adults in combination with other antiretroviral medications.
The following points should be considered when initiating therapy with Lexiva/ritonavir(Lexiva/r) in PI-experienced patients: the PI-experienced patient study wasnot large enough to reach a definitive conclusion that Lexiva/r and lopinavir/ritonavirare clinically equivalent lexiva. Once-daily administration of Lexiva plus ritonaviris not recommended for PI-experienced patients.
Lexiva was co-discovered by GSK and Vertex Pharmaceuticals. Lexiva, a PI that can be taken once or twice daily without food or water restrictions,has been evaluated in clinical trials with both PI-experienced and antiretroviraltherapy (ART)-naive HIV patients. Lexiva may be dosed three different ways: 1) two 700mg tablets twice daily(BID), 2) two 700mg tablets once daily (QD) in combination with two 100mg capsulesof ritonavir QD (Lexiva/r QD), or 3) one 700mg tablet BID in combination withone 100mg capsule of ritonavir BID (Lexiva/r BID) lexiva. For PI-experienced patients,the recommended dose is one 700mg tablet BID in combination with one 100mg capsuleof ritonavir BID lexiva. More than 1,200 people - both ART-naive and PI-experienced patients - participatedin three Phase III trials to test the safety and efficacy of Lexiva with andwithout ritonavir lexiva. In all three trials, study drugs were taken as part of combinationtherapy that included two nucleoside reverse transcriptase inhibitors lexiva. In theseclinical trials Lexiva demonstrated: Durable anti-viral response through 48 weeks of therapy in ART-naive patients(<400 copies/mL 66 percent to 69 percent)
All grade 2-4 drug-related adverse events < 10 percent in ART-naive patients
Significantly less grade 2-4 drug-related diarrhea than nelfinavir
All grade 2-4 drug-related adverse events < 13 percent in PI-experiencedpatients
Flexible once or twice daily options in ART-naive patients with no food or fluidrestrictions
No ART-naive patients receiving Lexiva/r developed any PI mutations lexiva. In PI-experiencedpatients, the following amprenavir resistance associated mutations were selectedeither alone or in combination: V32I, M46I/L, I47V, I50V, I54L/M and I84V lexiva. Theclinical significance of resistance data is currently under evaluation.
The following results were reported for each of the Phase III trials at 48-weeks: The NEAT Study
NEAT compared Lexiva with nelfinavir (NFV) in 249 ethnically and gender diverse,ART-naive patients, with advanced HIV disease (45 percent of patients had viralload >100,000 copies/mL, 48 percent had CD4+ cell count <200 cells/mm3,and 20 percent were CDC Class C) at entry lexiva. Patients took 1,400mg of Lexiva BIDor 1,250mg of NFV BID in combination with abacavir sulfate and lamivudine BID.
66 percent of patients taking Lexiva achieved undetectable viral load (<400copies/mL), compared to 52 percent of patients taking NFV lexiva.
Among patients with high baseline viral load (>100,000 copies/mL), 67 percentof 73 patients in the arm containing Lexiva achieved undetectable viral load(<400 copies/mL), compared to 36 percent of 37 patients in the NFV arm lexiva.
There was significantly less grade 2-4 drug-related diarrhea in patients receivingLexiva (5 percent) than in patients receiving NFV (18 percent) lexiva.
Protease mutations selected at the first failure timepoint with Lexiva (V32I+147Vor 154L/M) had limited cross-resistance to other PIs lexiva.
The most common adverse events were diarrhea, nausea, vomiting, headache andrash.
The SOLO Study
The SOLO Study reported results of 649 ethnically and gender diverse ART-naivepatients, with advanced HIV disease (43 percent of patients had viral load >100,000copies/mL, 55 percent had CD4+ cell count <200 cells/mm3, and 22 percentwere CDC Class C) at entry lexiva. Patients in the study took either 1,400mg Lexivawith 200mg ritonavir (Lexiva/r) QD, or 1,250mg NFV BID lexiva. Both PIs were administeredin combination with abacavir sulfate and lamivudine BID.
69 percent of patients taking Lexiva/r achieved undetectable viral load (<400copies/mL), compared to 68 percent of patients taking NFV lexiva.
Among patients with a high viral load (>100,000 copies/mL) at baseline, 66percent of 125 patients taking Lexiva/r QD achieved undetectable viral load(<400 copies/mL), compared to 64 percent of 133 patients taking NFV BID lexiva.
There was significantly less grade 2-4 drug-related diarrhea in patients receivingLexiva (10 percent) than in patients receiving NFV (18 percent) lexiva.
No protease mutations were observed through 48 weeks in the 32 patients whoexperienced virologic failure with Lexiva/r QD lexiva.
There were significantly fewer nucleoside reverse transcriptase inhibitor (NRTI)mutations observed after virologic failure with Lexiva/r QD (4 of 32 patients,or 13 percent) compared with NFV (30 of 54, or 56 percent) lexiva.
The most common adverse events were diarrhea, nausea, vomiting, headache andrash.
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