The U.S. Food and Drug Administration (FDA) approved, on October 20, 2003, a prodrug of the protease inhibitor (PI) amprenavir (APV). Approval for Lexiva (fosamprenavir), which is manufactured by GlaxoSmithKline and Vertex Pharmaceuticals, was based on two studies in antiretroviral-naive patients and one study in PI-experienced patients.

Antiretroviral-Naive Studies

In study APV30001, fosamprenavir 1,400 mg twice daily was compared to nelfinavir (NFV) 1,250 mg twice daily in 249 antiretroviral-naive patients. Both treatment groups also received abacavir (ABC) 300 mg twice daily and lamivudine (3TC) 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 percent (57 percent) for the fosamprenavir group and 52 percent (42 percent) for the NFV group. Through 48 weeks of therapy, the median increases from baseline in CD4 counts were 201 cells/mm³ in the group receiving fosamprenavir and 216 cells/mm³ in the NFV group.

In study APV30002, fosamprenavir 1,400 mg once daily plus ritonavir (RTV) 200 mg once daily was compared to NFV 1,250 mg twice daily in 649 treatment-naive patients. Both treatment groups also received ABC 300 mg twice daily and 3TC 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 69 percent (58 percent) for the fosamprenavir group and 68 percent (55 percent) for the NFV group. Through 48 weeks of therapy, the median increases from baseline in CD4 counts were 203 cells/mm³ in the group receiving fosamprenavir and 207 cells/mm³ in the NFV group.

PI-Experienced Study

In study APV30003, two different regimens of fosamprenavir plus RTV (fosamprenavir 700 mg twice daily plus RTV 100 mg twice daily or fosamprenavir 1,400 mg once daily plus RTV 200 mg once daily) were compared to lopinavir/ritonavir (LPV/r) 400 mg/100 mg twice daily in 315 patients who had experienced virologic failure to one or two prior PI-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 fosamprenavir/r and -1.67 log10 copies/mL for the LPV/r group.

The proportions of patients who achieved and maintained confirmed HIV-1 RNA <400 copies/mL were 58 percent with twice-daily fosamprenavir/r and 61 percent with LPV/r (95 percent CI for the difference -16.6, 10.1).

The proportions of patients with HIV-1 RNA <50 copies/mL with twice-daily fosamprenavir/r and with LPV/r were 46 percent and 50 percent, respectively (95 percent CI for the difference -18.3, 8.9). Through 48 weeks of therapy, the median increases from baseline in CD4 counts were 81 cells/mm³ with twice-daily fosamprenavir/r and 91 cells/mm³ with LPV/r.

The following points should be considered when initiating therapy with fosamprenavir/r in PI-experienced patients:

• The PI-experienced patient study was not large enough to reach a definitive conclusion that fosamprenavir/r and LPV/r are clinically equivalent.

• Once-daily administration of fosamprenavir plus RTV is not recommended for PI-experienced patients.

The most common treatment-emergent adverse events in clinical studies of fosamprenavir 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 percent of patients receiving fosamprenavir and in 5.9 percent of patients receiving comparator treatments.