Merck’s HIV therapy Delstrigo achieves primary efficacy endpoint in phase 3 study

Merck has announced the first presentation of data from the Phase 3 DRIVE-SHIFT trial evaluating a switch of medication to Delstrigo , a once-daily fixed-dose combination tablet of doravirine (100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg), in adults with HIV-1 infection who demonstrated virological suppression for at least six months on a stable antiretroviral treatment regimen.

The study met its primary endpoint of non-inferior efficacy as measured by the proportion of participants who switched to DELSTRIGO and had plasma HIV-1 RNA levels <50 copies/mL at Week 48 compared to the proportion of participants who continued on their baseline regimen and had HIV-1 RNA levels <50 copies/mL at Week 24. These study results will be presented today as a late-breaking oral presentation at IDWeek 2018 taking place Oct. 3-7, 2018, in San Francisco.

MedStar Georgetown University Hospital infectious diseases division Dr. Princy Kumar said: “These data build on the existing clinical profile of DELSTRIGO as seen in treatment-naïve patients, and suggests its potential to address a broader population.

“Data from this trial support another possible future option for people living with HIV, many of whom may require a change to a different treatment regimen.”

In the DRIVE-SHIFT study, 670 participants who demonstrated virological suppression (undetectable HIV-1 RNA) on an antiretroviral regimen for at least six months were randomized to begin treatment with DELSTRIGO (doravirine/3TC/TDF) immediately on Day 1 (immediate switch group, ISG; N=447) or after 24 weeks (delayed switch group, DSG; N=223).

The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL, with the primary comparison between the DELSTRIGO ISG at Week 48 and baseline regimen DSG at Week 24, and a secondary comparison between the DELSTRIGO ISG and baseline regimen DSG at Week 24.

In the study, DELSTRIGO-receiving participants in the ISG maintained virologic control at the 48-week timepoint:

90.8 percent (406/447) of participants who switched to DELSTRIGO on Day 1 (ISG) had HIV-1 RNA <50 copies/mL at Week 48; in comparison, 94.6 percent (211/223) of participants who continued on their baseline regimen (DSG) had HIV-1 RNA <50 copies/mL at Week 24 (treatment difference: -3.8%, 95% confidence interval: -7.9, 0.3).

1.6 percent in the DELSTRIGO ISG group had HIV-1 RNA ≥50 copies/mL at Week 48 compared to 1.8 percent in the baseline regimen DSG group at Week 24 (treatment difference: -0.2%, 95% confidence interval: -2.5, 2.1).

Secondary comparisons were also made at Week 24 for both treatment groups. DELSTRIGO-receiving participants in the ISG also maintained virologic control at this earlier (Week 24) timepoint:

93.7 percent (419/447) of participants who switched to DELSTRIGO on Day 1 (ISG) had HIV-1 RNA <50 copies/mL, compared with 94.6 percent (211/223) of those who continued on their baseline regimen (DSG) (treatment difference: -0.9%; 95% confidence interval: -4.7, 3.0).

1.8 percent in both treatment groups had HIV-1 RNA ≥50 copies/mL at Week 24 (treatment difference: 0.0%; 95% confidence interval: -2.3, 2.3).

No genotypic or phenotypic resistance to any study drug was observed in participants taking DELSTRIGO through 48 weeks of treatment.

At Week 24, participants who switched to DELSTRIGO on Day 1 showed statistically significant decreases in fasting LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) compared to those who continued on a boosted protease inhibitor regimen (LDL-C: -16.5 mg/dL vs. -1.9 mg/dL, treatment difference: -14.7, 95% confidence interval: -18.9, -10.4, p<0.0001; non-HDL-C: -24.7 mg/dL vs. -1.3 mg/dL, treatment difference: -23.0, 95% confidence interval: -28.0, -18.1, p<0.0001).

At this timepoint, DELSTRIGO (doravirine/3TC/TDF) also showed decreases in cholesterol and triglyceride levels (cholesterol: -26.2 mg/dL vs. 0.5 mg/dL, treatment difference: -25.8, 95% confidence interval: -31.0, -20.7; triglycerides: -43.2 mg/dL vs. 0.9 mg/dL, treatment difference: -42.9, 95% confidence interval: -59.1, -26.7).

The most common adverse events (>5% incidence in any group) in the DELSTRIGO ISG group through Week 24, the baseline regimen DSG group through Week 24, and the DSG group after the delayed switch to DELSTRIGO (Week 24 to Week 48) were nasopharyngitis (7.4%; 5.4%; 4.3%, respectively) and headache (6.5%; 2.2%; 6.7%, respectively).

The most common drug-related adverse event (>2% incidence in any group) was headache (1.6%; 0.4%; 2.4%, respectively). The rates of discontinuation of therapy due to adverse events through Week 24 were 2.5% in the DELSTRIGO ISG group and 0.4% in the baseline regimen DSG group.

Merck Research Laboratories global clinical development infectious diseases therapeutic area head  and vice president Dr George Hanna said: “Merck’s dedication over the past several decades to improving HIV treatment and care has always been focused on addressing unmet needs. People living with HIV need new treatment options.

“The data from DRIVE-SHIFT suggest the clinical potential of DELSTRIGO to serve as a new fixed-dose combination option for those considering a change in their HIV antiretroviral treatment regimen.”

DRIVE-SHIFT is a Phase 3 multicenter, open-label, randomized, active-controlled, non-inferiority clinical trial evaluating a switch to DELSTRIGO compared with continuation of current therapy in adults with HIV-1 infection who were virologically suppressed (undetectable plasma HIV-1 RNA levels <40 copies/mL) for at least six months on a stable regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a boosted protease inhibitor, boosted elvitegravir, or NNRTI.

Participants with screening HIV-1 RNA <40 copies/mL, no history of virologic failure on any regimen, and no resistance to DELSTRIGO were randomized (2:1) to start DELSTRIGO on Day 1 (ISG) or after 24 weeks (DSG).

The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL, with the primary comparison between the DELSTRIGO ISG at Week 48 and baseline regimen DSG at Week 24 and a secondary comparison between the treatment groups at Week 24.

Source: Company Press Release