FDA Approves Duo of HIV Medications

A pair of new supplemental HIV-medications will soon be available, after the US Food and Drug Administration (FDA) approved doravirine (Pifeltro) and doravirine/lamivudine/tenofovir disoproxil fumarate (Delstrigo) supplemental New Drug Applications (sNDA).

The new drugs, produced by Merck, allows treatment-experienced adults living with HIV, who are virally suppressed and have no prior history of treatment failure, to switch to either of the treatment options.

Doravirine is a 100 mg, once-daily, non-nucleoside reverse transcriptase inhibitor (NNRTI), while doravirine/lamivudine/tenofovir disoproxil fumarate is a once-daily fixed-dose combination tablet of 100 mg doravirine, 3TC/300 mg lamivudine, and TDF/300 mg tenofovir disoproxil fumarate.

Both treatments received FDA approval in 2018 for adult patients with no documentation of past antiretroviral therapy.

“Today’s approvals provide doravirine treatment options for people living with HIV-1 who are virally suppressed, reflecting Merck’s continued commitment to research and development of HIV treatments,” George Hanna, MD, vice president and therapeutic area head of infectious diseases, Global Clinical Development, Merck Research Laboratories, said in a statement. “We are thankful to the researchers and HIV community for their collaboration that made this possible.”

The recent approval was based on the DRIVE-SHIFT study, which evaluated a switch to doravirine/lamivudine/tenofovir disoproxil fumarate compared to continuing a baseline regimen of 2 nucleoside reverse transcriptase inhibitors, plus a boosted protease inhibitor, boosted elvitegravir, or NNRTI.

The study met its primary endpoint, demonstrating non-inferior efficacy, which was measured by the proportion of patients who switched therapy and had plasma HIV-1 RNA levels <50 copies/mL through week 48, compared to participants who continued their baseline regimen and had HIV-1RNA levels <50 copies/mL at week 24.

The most common adverse reactions observed with doravirine/lamivudine/tenofovir disoproxil fumarate in clinical studies were dizziness (7%), nausea (5%), and abnormal dreams (5%). The most common adverse reactions with doravirine were nausea (7%), dizziness (7%), headache (6%), fatigue (6%), diarrhea (5%), abdominal pain (5%), and abnormal dreams (5%).

In the phase 3 trial, 2 participants in the delayed switch group and 6 patients in the immediate switch group met the protocol-defined virologic failure criteria.

In both doravirine treatment arms of the 2 DRIVE-AHEAD and DRIVE-FORWARD studies, 11 of 747 total participants showed the emergence of doravirine-associated resistance substitutions (among the 28 participants with HIV-1 RNA >400 copies per mL at virologic failure or early study discontinuation and having resistance data).

Of the 11 participants, 7 showed both genotypic and phenotypic resistance to doravirine, with at least a 100-fold reduction in susceptibility to doravirine, while the other 4 participants had substitutions that were associated with less than 2-fold reduction in susceptibility to doravirine.

This article was originally published in Contagion® Live.