Doravirine and Islatravir Combination Shown to be Noninferior to Once-Daily ART
In a blinded phase 3 study, doravirine and islatravir was compared to antiretroviral therapy, BIC/FTC/TAF (Biktarvy), and it was shown that there was no between-group differences in mean change in CD4 T-cell or total lymphocyte count at week 48.
At CROI today, Merck presented results of its investigational combination therapy of doravirine and islatravir (DOR/ISL) showing it was noninferior to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).1
“At week 48, HIV-1 RNA was ≥50 c/mL in 5 (1.5%) participants on DOR/ISL and 1 (0.6%) on BIC/FTC/TAF (difference 0.9%, 95% CI -1.9, 2.9; CI upper bound <4%), demonstrating non-inferiority of DOR/ISL to BIC/FTC/TAF. HIV-1 RNA was <50 c/mL in 91.5% of participants on DOR/ISL and 94.2% on BIC/FTC/TAF,” the investigators wrote in the abstract.1
“At week 48, the proportion of individuals that maintain their viral suppression was the same between the 2 groups," said Luisa Stamm, MD, PhD, associate vice president, Infectious Disease Clinical Research, section head, HIV, Merck. "So we did meet our noninferiority primary efficacy endpoint with over 90% of individuals in both treatment groups maintaining viral suppression."
In this double-blind, non-inferiority phase 3 study, adults with HIV, and viral suppression for approximately 3 months on BIC/FTC/TAF, and no history of treatment failure or known resistance to doravirine were randomized (2:1) to switch to doravirine and islatravir (100/0.25 mg) or continue BIC/FTC/TAF. Primary efficacy endpoint was the percentage of participants with HIV-1 RNA ≥50 c/mL at week 48). 1
“Discontinuation was required for confirmed decline in total lymphocytes (≥30% and to <1.0 x109/L) or in CD4 T-cell count (≥30% and to <350 cells/mm3 from baseline ≥350 or to <200 from baseline ≤349),” the investigators wrote. “There were no between-group differences in mean change in CD4 T-cell or total lymphocyte count at week 48. Two participants on DOR/ISL (0.6%) and one on BIC/FTC/TAF (0.6%) discontinued due to decrease in CD4 T-cell or total lymphocyte count.”1
Merck is also presenting data at CROI on an open-label phase 3 study examining doravirine and islatravir compared to a baseline antiretroviral therapy.
“Switching to DOR/ISL (100/0.25 mg) maintained viral suppression and was noninferior to continuing bART at week 48. DOR/ISL was well tolerated with a similar safety profile to bART and did not adversely affect lymphocytes,” the investigators wrote.2
“The endpoint was similar, and we met noninferiority comparing doravirine/ islatravir to baseline antiretroviral therapy. And again, high rates of viral suppression, over 90% for both treatment groups, and similarly, the doravirine/islatravir group had comparable safety to the comparator group. And lastly, as we just discussed, we saw no impacts on total lymphocytes and CD-4 counts,” Stamm said.
In terms of next steps, Merck is working towards regulatory approval for the combination therapy.
“We are really excited about these positive results, and we're working furiously to put it together into our regulatory filing right now," said Stamm. “We'll have some updates on when we can anticipate that completion of the filing and the approval when they're available.”
