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FDA Approves LEXIVA (Fosamprenavir calcium) to Treat HIV Infection
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Accession Number
A00686
Author
US Department of Health and Human Services (HHS), Food and Drug Administration (FDA)
Source
FDA Medical Bulletin
Release Date
October 21, 2003
Major Descriptors
Antiretroviral therapy
Antiretrovirals
FDA
FDA approval
Protease Inhibitors
Topic
Drugs and Treatment
Text
The Food and Drug Administration (FDA) approved, on October 20, 2003, LEXIVA (Fosamprenavir calcium), manufactured by GlaxoSmithKline of Research Triangle Park, NC and Vertex Pharmaceuticals, Incorporated of Cambridge, MA.
LEXIVA is a prodrug of amprenavir, a protease inhibitor used to treat infection with the human immunodeficiency virus (HIV-1). LEXIVA is rapidly converted to amprenavir by cellular or serum phosphatases in the body.
LEXIVA is indicated in combination with other antiretroviral agents for the treatment of HIV infection in adults. The approval of LEXIVA was based on two studies in antiretroviral naïve patients and one study in protease inhibitor experienced patients.
Antiretroviral Naïve Studies:
In study APV30001, LEXIVA (1400 mg twice daily) was compared to nelfinavir (1250 mg twice daily) in 249 antiretroviral naïve patients. Both treatment groups also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).
The proportions of patients who achieved and maintained confirmed HIV RNA < 400 copies/mL (< 50 copies/mL) through week 48 was 66% (57%) for the LEXIVA group and 52% (42%) for the nelfinavir group, respectively. Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 201 cells/mm3 in the group receiving LEXIVA and 216 cells/mm3 in the nelfinavir group.
In study APV30002, LEXIVA (1,400 mg once daily) plus ritonavir (200 mg once daily) was compared to nelfinavir (1,250 mg twice daily) in 649 treatment-naive patients. Both treatment groups also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).
The proportions of patients who achieved and maintained confirmed HIV RNA < 400 copies/mL (< 50copies/mL) through week 48 was 69% (58%) for the LEXIVA group and 68% (55%) for the nelfinavir group, respectively. Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 203 cells/mm3 in the group receiving LEXIVA and 207 cells/mm3 in the nelfinavir group.
Protease Inhibitor Experienced Study
In study APV30003, two different regimens of LEXIVA plus ritonavir (LEXIVA 700 mg twice daily plus ritonavir 100 mg twice daily or LEXIVA 1,400 mg once daily plus ritonavir 200 mg once daily) was compared to lopinavir/ritonavir (400 mg/100 mg twice daily) in 315 patients who had experienced virologic failure to 1 or 2 prior protease inhibitor-containing regimens.
The time-averaged changes in plasma HIV-1 RNA from baseline (AAUCMB) at 48 weeks (the endpoint on which the study was powered) were -1.4 log10 copies/mL for twice-daily LEXIVA/ritonavir and -1.67 log10 copies/mL for the lopinavir/ritonavir group.
The proportions of patients who achieved and maintained confirmed HIV-1 RNA <400 copies/mL were 58% with twice-daily LEXIVA/ritonavir and 61% with lopinavir/ritonavir (95% CI for the difference -16.6, 10.1).
The proportions of patients with HIV-1 RNA <50 copies/mL with twice-daily LEXIVA/ritonavir and with lopinavir/ritonavir were 46% and 50%, respectively (95% CI for the difference -18.3, 8.9). Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 81 cells/mm3 with twice-daily LEXIVA/ritonavir and 91 cells/mm3 with lopinavir/ritonavir
The following points should be considered when initiating therapy with LEXIVA/ritonavir in protease inhibitor-experienced patients:
The protease inhibitor-experienced patient study was not large enough to reach a definitive conclusion that LEXIVA/ritonavir and lopinavir/ritonavir are clinically equivalent. Once-daily administration of LEXIVA plus ritonavir is not recommended for protease inhibitor-experienced patients.
The most common treatment-emergent adverse events in clinical studies of LEXIVA were diarrhea, nausea, vomiting, headache, and rash and were generally mild to moderate in severity. Treatment discontinuation due to adverse events occurred in 6.4% of patients receiving LEXIVA and in 5.9% of patients receiving comparator treatments.
LEXIVA tablets are available for oral administration in a strength of 700 mg of fosamprenavir as fosamprenavir calcium (equivalent to approximately 600 mg of amprenavir).
LEXIVA Tablets may be taken with or without food.
The recommended oral dose of LEXIVA, alone or in combination with ritonavir, is as follows:
Therapy-Naive Patients:
LEXIVA 1,400 mg twice daily (without ritonavir)
LEXIVA 1,400 mg once daily plus ritonavir 200 mg once daily
LEXIVA 700 mg twice daily plus ritonavir 100 mg twice daily
The twice-daily plus ritonavir dose is supported by pharmacokinetic and safety data.
Protease Inhibitor-Experienced Patients:
LEXIVA 700 mg twice daily plus ritonavir 100 mg twice daily
Once-daily administration of LEXIVA plus ritonavir is not recommended in protease inhibitor-experienced patients.
Ritonivir is used to increase the plasma concentration of LEXIVA.
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