Long-term safety and efficacy data from the pivotal phase 3 EMERALD trial were presented at ID Week 2018.
Patients with HIV-1 who switched over to a once-daily, single-tablet regimen of darunavir 200 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (D/C/F/TAF), marketed as SYMTUZA, had maintained high virologic suppression rates with no resistance development at 96 weeks.
New 96-week data from the pivotal phase 3 EMERALD trial were presented by Joseph Eron, Jr. MD, professor of medicine from the University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, at ID Week 2018, held this year in San Francisco, California.
“The 96-week results from the EMERALD study demonstrate that SYMTUZA can offer clinically appropriate people living with HIV a single-tablet option that may help them maintain high rates of virologic suppression over time,” Dr. Eron said in a recent statement.
In the randomized, active-controlled, open-label, noninferiority phase 3 trial, virologically suppressed (VL <50c/mL for ≥2 months), HIV-infected adults were randomized (2:1) to continue on boosted-protease inhibitors (bPI) plus emtricitabine/tenofovir disoproxil fumarate (F/TDF) or to switch over to D/C/F/TAF over 48 weeks. Patients could either continue on the D/C/F/TAF regimen or switch from the bPI F/TDF regimen over to D/C/F/TAF at week 52 (late switch, 44 weeks D/C/F/TAF exposure) in a single-arm extension phase of the trial, up until week 96.
The primary and secondary endpoints of the trial were the percentage of patients with virologic rebound (confirmed VL ≥50 c/mL) cumulative through week 48 and week 96, respectively, according to Dr. Eron and colleagues.
The investigators report that 1080 patients out of the total 1141 patients who were randomized and treated continued on to the extension phase of the trial; of the 1080 patients, 728 continued to receive the D/C/F/TAF regimen, while 352 switched over from bPI F/TDF to D/C/F/TAF.
Dr. Eron reported that few patients in the D/C/F/TAF treatment arm experienced virologic rebound cumulative through week 96 (3.1%, 24/763); virologic rebound occurred in 2.3% (8/352) of patients in the late switch arm. However, many of the patients who rebounded resuppressed at week 96 (14/24, D/C/F/TAF and 2/8, late switch).
A high percentage, 90.7% (602/763), of those in the D/C/F/TAF arm were suppressed at week 96. After 44 weeks of treatment, 93.8% (330/352) of patients in the late switch arm maintained virologic suppression. Virologic failure (≥50 c/mL) rates for D/C/F/TAF were 1% (9/763) at week 96 and 2% (6/352) after 44 weeks of D/C/F/TAF exposure in the late switch arm at week 96.
No darunavir, primary protease inhibitor, tenofovir, or emtricitabine resistance-associated mutations were seen post-baseline.
Overall, D/C/F/TAF was found to be well tolerated with few serious adverse events (9%, 66/763) and treatment-associated discontinuations (2%, [17/763]) observed over 96 weeks. Over 44 weeks, 6% (21/352) and 2% (7/352) in the late switch group experienced serious adverse events and treatment-associated discontinuations.
The most common adverse events in the extension period were as follows: upper respiratory tract infection (16%, 122/763), viral upper respiratory tract (13%, 98/763), diarrhea (11%, 80/763), headache (10%, 79/763), and back pain (10%, 79/763).
Investigators observed improvements in renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late switch arm (week 52 to 96), with a small change in TC/HDL-C ratio, which investigators deemed to be consistent with the known effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide based regimens.
“Switching to D/C/F/TAF maintained high virologic suppression rates (>90%) at week 96 with no resistance development, and was well-tolerated over 96 weeks with bone, renal, and lipid safety consistent with known TAF and cobicistat profiles,” the authors write.
The 96-week extension study reinforced the long-term safety, efficacy, and resistance profile of D/C/F/TAF previously demonstrated at 24 and 48 weeks in virologically suppressed adult patients with HIV-1.
“D/C/F/TAF combines the efficacy and high genetic barrier to resistance of darunavir with the safety benefits of TAF, even in patients with a history of non-DRV VF,” Dr. Eron and colleagues conclude.
J. Eron Jr., Gilead: Consultant and Grant Investigator, Consulting fee and Research grant. Janssen: Consultant, Consulting fee and Research grant; C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support; D. Cunningham, Janssen: Investigator, Research grant. Gilead: Investigator, Research grant; F. Pulido, Janssen: Consultant, Investigator and Scientific Advisor, Consulting fee, Research support, and Speaker honorarium; F. Post, Gilead: Consultant and Grant Investigator, Consulting fee and Grant recipient. Viiv: Grant Investigator, Grant recipient. Janssen: Consultant, Consulting fee. MSD: Consultant, Consulting fee; S. De Wit, Janssen: Investigator, Research grant; E. Lathouwers, Janssen: Employee and Shareholder, Salary; V. Hufkens, Janssen: Employee and Shareholder, Salary; R. Petrovic, Janssen R&D: Independent Contractor, Consulting fee; E. Van Landuyt, Janssen: Employee and Shareholder, Salary.