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.
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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