MSD’s once-daily pill for human immunodeficiency virus (HIV) has proved non-inferior to Gilead’s Biktarvy (bictegravir/emtricitabine/tenofovir alafenamidei) in a Phase III trial.
In the randomised, double-blind study (NCT05705349), the two-drug, single-tablet regimen of Pifeltro (doravirine), and islatravir, (DOR/ISL), met its primary endpoint of percentage of participants with HIV-1 RNA levels <50 copies/mL at week 48, matching that of standard of care (SoC) Biktarvy in treatment-naïve adults with HIV-1 infection.
Pifeltro is a non-nucleoside reverse transcriptase inhibitor (NNRTI) while islatravir is an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI).
The primary safety objective of the trial was also met, with the safety profile of DOR/ISL being comparable to Biktarvy at the same time point.
The US Food and Drug Administration (FDA) has accepted the new drug application (NDA) for DOR/ISL for the treatment of adult HIV patients to replace the current antiretroviral regimen in those who are virologically suppressed. The FDA has set a target action date of 28 April 2026 under the Prescription Drug User Fee Act (PDUFA).
MSD's senior vice-president, head of global clinical development and chief medical officer Dr Eliav Barr said: “We are encouraged by the results from this Phase III trial with DOR/ISL, evaluating the regimen in adults with HIV who have not previously taken antiretroviral treatments.
"DOR/ISL is the first two-drug regimen without an integrase inhibitor showing non-inferior efficacy and safety when compared to the three-drug INSTI-based regimen Biktarvy in this population.
“These data support the potential for this regimen to be a meaningful treatment option for virally suppressed people living with HIV who are looking to switch to a new regimen or people who have not previously been on antiretroviral therapy to start treatment."
If approved, GlobalData’s patient-based forecast predicts the single-tablet regiment will bring in $1.75bn in 2033.
GlobalData is the parent company of Clinical Trials Arena.
MSD will present detailed findings from the trial at a future scientific congress.
HIV landscape gains recent boost
This comes just days after Gilead announced its once-daily, single pill regimen of bictegravir 75mg, an integrase strand transfer inhibitor (INSTI), and lenacapavir 50mg, an HIV capsid inhibitor (BIC/LEN), also showed success as an anti-retroviral therapy (ART). The trial found the single-tablet regimen to be non-inferior to multi-tablet ART.
Gilead and MSD are also collaborating on a once-weekly HIV treatment. In the ongoing, open-label Phase II study (NCT05052996), 88.5% and 100% of adults treated with the once-weekly treatment of MSD’s islatravir and Gilead’s lenacapavir maintained undetectable viral load (HIV-1 RNA <50 copies/mL) at week 96. The combination is already being evaluated in Phase III trials (NCT06630286 and NCT06630299).
On the prevention side, Gilead seems to have the upper hand with its twice-yearly Yeztugo (lenacapavir), which touted near perfect efficacy in the PURPOSE programme. The drug has since been approved in several countries, including the US, and the big pharma said it will make generic versions available for low- and middle-income countries where HIV is prevalent to ensure access.
GlobalData predicts the HIV market to surpass $32.1bn across the seven major markets (7MM: US, France, Germany, Italy, Spain, the UK, and Japan) in 2033, increasing by a 1.9% compound annual growth rate (CAGR) compared to 2023.
