• The NEAT Study: GW433908 Efficacy and Safety in Antiretroviral Therapy-Naive Subjects: Preliminary 24-Week Results (Abstract H-166)
  Authored by J.P. Nadler, A. Rodriguez-French
  Poster Presentation: View the original abstract

The development of GW433908, the calcium phosphate ester pro-drug of amprenavir (APV, amprenavir), continues slowly but steadily. By now it is clear that this compound is more potent than the current APV parent formulation. In naive populations it has been shown to decrease HIV-1 RNA levels by 2.0 log c/mL, when given in combination with two nucleosides. It has a flexible-dosing schedule that allows for twice a day or once a day dosing, when boosted with ritonavir (RTV, Norvir). It appears to be well, if not better, tolerated than amprenavir. Also, as with amprenavir, its resistance profile offers several advantages with less cross-resistance to other protease inhibitors.

The NEAT study is an ongoing venture from GlaxoSmithKline (GSK) to evaluate the efficacy and safety of GW433908 (or 908) in comparison with nelfinavir (NFV, Viracept) in antiretroviral therapy (ART)-naive subjects. In this study, antiretroviral therapy-naive patients were randomized 2:1 to receive either open-label 908 (1,400 mg twice a day) or nelfinavir, both in combination with standard dosages of lamivudine (3TC, Epivir) and abacavir (ABC, Ziagen) also given twice a day. The study patients were stratified in two groups based on their baseline HIV-1 RNA levels: greater than 5,000-100,000 and greater than 100,000 c/mL. In this poster, Dr. Nadler presented the initial 24-week data.

A total of 249 subjects were enrolled in this study: 166 in the 908 arm and 83 in the nelfinavir arm. The baseline characteristics for both groups were similar. A large percentage of patients (22 percent) discontinued the study, but discontinuation due to adverse events was few (5 percent) and similar between both groups.

Efficacy data showed that the proportion of subjects achieving an undetectable viral load less than 400 copies/mL was superior in the 908 arm to the nelfinavir arm. When looking at the virologic response by screening HIV-1 RNA, the proportion of subjects achieving an undetectable viral load (both less than 400, and less than 50 c/mL) was better in the 908 group than in the nelfinavir group. At high HIV-1 RNA levels (greater than 100,000 c/mL) more patients in the 908 arm were able to achieve viral loads below the level of quantification.

The development of adverse events in this study was similar in both arms, with more diarrhea seen in the nelfinavir arm, but more allergic reactions and rashes seen in the 908 arm. The proportion of subjects stopping ABC due to possible ABC-HSR was high, but also similar in both groups (10 percent in 908 arm and 8 percent in the nelfinavir arm). Lipid and glucose abnormalities were rare and not significantly different between both groups.

As 908 becomes more advanced in development, it will be clear that studies like this one are important to elucidate the most appropriate nucleoside combination. Despite the high rate of discontinuation, the efficacy of 908 in comparison with nelfinavir was found to be comparable and non-inferior, with a trend to superiority in subjects with high viral loads. Given the fact that 908 has been found to be fairly well tolerated and potent, it is refreshing to see that the incidence of adverse reactions also appears to be favorable. Without doubt, 908 is placing itself as a very good alternative to treat diverse populations including antiretroviral therapy-naive patients.

Personally, after having the opportunity to use 908 in several patients under clinical trials, I look forward to the formal FDA approval of 908 (hopefully by the spring of 2003), which without doubt is going to benefit other patient populations.