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Integrase Inhibitor GSK744 Safe, Effective as Once-Daily Oral Pill

By Warren Tong

October 21, 2013

GSK744, an investigational integrase inhibitor, performed well when taken once daily orally, according to study results presented at EACS 2013 in Brussels, Belgium.

The 24-week data, presented by David Margolis, M.D., showed that GSK744 -- also known variously as S/GSK1265744 or simply "744" -- was safe and efficacious for treatment-naive patients, and works best when taken at 30 mg per day.

The partially blinded dose-finding study followed 243 individuals who were split into four groups:

For all groups, the two NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors) were either abacavir/lamivudine (Epzicom, Kivexa) or tenofovir/emtricitabine (Truvada).

The median age of the groups was about 34 years. More than 93% were male, about 60% were white and about 30% were African American. The median viral load was around 20,000 copies/mL and the median CD4+ cell count was about 415 cells/mm3.

In a snapshot analysis at week 24, GSK744 showed high rates of virologic success, defined as a viral load below 50. The three GSK744 dose groups showed an average success rate of about 87%, compared to a 74% virologic success rate for the efavirenz group.

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The median increase in CD4+ cell count at week 24 was also good for all three GSK744 groups, at 185.5 cells/mm3, compared to 159 for the efavirenz group.

Protocol-defined virologic failure in this study was a viral load decrease of less than 10 copies/mL by week 4, or a viral load above 200 at week 16 (or after prior suppression below 200). Overall, there were three instances (2%) in the GSK744 groups and three (5%) in the efavirenz group. However, after phenotype and genotype testing, the researchers found no integrase, NNRTI (non- nucleoside reverse transcriptase inhibitor) or NRTI mutations in any patients.

By week 24, eight patients (13%) withdrew from the 10-mg group, seven (12%) withdrew from the 30-mg group and six (10%) withdrew from the 60-mg group. Overall, 21 (12%) withdrew from the GSK744 groups compared to 16 (26%) who withdrew from the efavirenz group. The reasons varied, but in terms of withdrawal because of adverse events, zero withdrew from the 10-mg group, one (2%) from the 30-mg group, three (5%) from the 60-mg group and seven (11%) from the efavirenz group.

In terms of withdrawal because of lack of efficacy, four (7%) withdrew from the 10-mg group, one (2%) from the 30-mg group, two (3%) from the 60-mg group and four (6%) from the efavirenz group. However, Margolis pointed out that three volunteers in the 10-mg group, one in the 60-mg group and one in the efavirenz group withdrew with a viral load between 51 and 189 copies/mL, just missing the below-50 cutoff that was an endpoint of the study.

The most common adverse event was headache, found more in the GSK744 groups (21%) than the efavirenz group (11%); the headaches were mostly grade 1 or 2 and did not lead to any withdrawals.

Based on this 24-week data, the researchers concluded that GSK744 at 30 mg is best for treatment-naive patients if the drug is dosed once-daily. The study is ongoing, but it will also help inform a separate phase-2b study in which GSK744 is being investigated as a long-acting drug used once monthly or quarterly.

Warren Tong is the research editor for TheBody.com and TheBodyPRO.com.

Follow Warren on Twitter: @WarrenAtTheBody.


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