Gilead's HIV Quad pill tops Atripla in neurological safety
This article was originally published in Scrip
Updated data presented by Gilead Sciences on 7 March revealed that its experimental once-daily, fixed-dose, four-in-one HIV pill Quad not only was as effective as the company’s US FDA-approved drug Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate), but its safety was comparable, and in fact beat the triple-combo medicine in demonstrating fewer adverse neurological effects.
Gilead reported the top-line results last August for its study 102, which met its primary objective of noninferiority of 88% of Quad patients achieving viral load of less than 50 copies/mL through week 48 versus 84% in the Atripla group, with a 95% confidence interval of -1.6% to 8.8% (scripintelligence, 16 August 2011).
The company reported last summer that the frequency of grade 3 and 4 adverse events and laboratory abnormalities was similar between the two arms and discontinuation rates were comparable.
But the Foster City, California-based biotech had kept most of the details about the safety data close the vest on Quad – emtricitabine, tenofovir disoproxil fumarate, evitegravir and cobicistat – until it presented the full results of study 102 on 7 March at the 2012 Conference on Retroviruses and Opportunistic Infections in Seattle.
In a conference call with investors and analysts, Dr Paul Sax, head of the HIV program and infectious diseases at Brigham and Women's Hospital in Boston and the principal investigator of study 102, said results of the double-blind Phase III trial showed that 4% of Quad patients and 5% of those on Atripla discontinued treatment due to adverse events.
Dr Sax said that among the adverse events occurring in at least 10% of patients, adverse neuropsychiatric effects were less common among Quad patients, with 15% experiencing abnormal dreams versus 27% for Atripla, while 7% of those on Quad had dizziness, compared with 24% taking Atripla. He noted that 9% of Quad patients experienced insomnia, versus 14% on Atripla.
Rash also was less likely to occur among Quad patients, 6% versus 12% for Atripla, a combination of two nucleoside analogue HIV-1 reverse transcriptase inhibitors and one non-nucleoside HIV-1 reverse transcriptase inhibitor indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.
Another plus for Quad was that it demonstrated lower increases in total cholesterol and low-density lipoprotein versus Atripla.
But on the downside, those on Quad experienced higher rates of nausea, 21% compared with 14% on Atripla, although Dr Sax said most of those were grade 1 and that there was no difference between the two study arms in the higher grades of nausea. He noted that only one patient discontinued the study due to that adverse effect.
Dr Sax added that the nausea was seen mostly when dosing started and "did not necessarily persist over time".
He also pointed out that 1.4% of patients discontinued study 102 because of adverse renal events. The median increases in serum creatinine were 0.14mg/dL for Quad and 0.01mg/dL for Atripla.
But Dr Norbert Bischofberger, Gilead's chief scientific officer, said those events are not primary clinical concerns and "can be dealt with fairly in a straightforward way".
Shares of Gilead closed at $45.48 on 7 March, a loss of 40 cents.