Merck presented 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.
“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,” said Dr. Princy Kumar, chief, Division of Infectious Diseases and Tropical Medicine at MedStar Georgetown University Hospital and professor of medicine and microbiology, Georgetown University School of Medicine, Washington, D.C. “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.”
Data from DRIVE-SHIFT
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 percent, 95 percent 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 percent, 95 percent 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 percent; 95 percent 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 percent; 95 percent 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 percent 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 percent 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 percent confidence interval: -31.0, -20.7; triglycerides: -43.2 mg/dL vs. 0.9 mg/dL, treatment difference: -42.9, 95 percent confidence interval: -59.1, -26.7).
The most common adverse events (>5 percent 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 percent; 5.4 percent; 4.3 percent, respectively) and headache (6.5 percent; 2.2 percent; 6.7 percent, respectively). The most common drug-related adverse event (>2 percent incidence in any group) was headache (1.6 percent; 0.4 percent; 2.4 percent, respectively). The rates of discontinuation of therapy due to adverse events through Week 24 were 2.5 percent in the Delstrigo ISG group and 0.4 percent in the baseline regimen DSG group.
“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,” said Dr. George Hanna, vice president and therapeutic area head of infectious diseases, global clinical development, Merck Research Laboratories. “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.”
On Aug. 30, 2018, Delstrigo (doravirine/3TC/TDF) was approved by the FDA for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment experience and is administered orally once daily with or without food.
(Source: Merck)
Filed Under: Drug Discovery