Delstrigo · HIV infection
Development and Regulatory status
Nov 18: Approved in EU .
Oct 18: 96-week data announced from PIII DRIVE-AHEAD study in treatment-naïve adults with HIV-1 infection. After 96 weeks of treatment, plasma HIV-1 RNA levels < 50 copies/mL was achieved in 77.5% of patients treated with Delstrigo™ and 73.6% in those treated with efavirenz/emtricitabine/tenofovir disoproxil fumarate (treatment difference 3.8%, 95% CI[-2.4 to 10.0]. Findings were consistent with those previously reported at 48 weeks, with no additional viral drug resistance to doravirine observed between Week 48 and Week 96. Rate of treatment discontinuation due to side-effects was lower in the Delstrigo™ group (3% v 7%), as was the mean change in levels of fasting lipids (LDL-C: treatment difference -11.1mg/dL [-14.8 to -7.4]; non-HDL-C: treatment difference: -17.0mg/dL [-21.1 to -13.0] .
Oct 18: Data from PIII DRIVE-SHIFT study on switching to doravirine/lamivudine/tenofovir disoproxil fumarate (Delstrigo™) in adults with HIV-1 on a stable antiretroviral therapy announced at conference. In patients virologically suppressed for at least six months on a stable antiretroviral regimen, switching to Delstrigo™ was non-inferior to continuation of the initial regimen in terms of plasma HIV-1 RNA levels <50 copies/mL (treatment difference -3.8% [-7.9 to 0.3] .
Sept 18: recommended for EU approval by CHMP - the full indication is "for the treatment of adults infected with HIV-1 without past or present evidence of resistance to the NNRTI class, lamivudine, or tenofovir (see sections 4.4 and 5.1)." It is proposed that it be prescribed by physicians experienced in the management of HIV infection. .
Aug 18: Approved by the FDA .
Jan 18: FDA accepts NDA for oral doravirine/lamivudine/tenofovir disoproxil fumarate for HIV-1 infections (Combination therapy, Treatment-naive) in USA with a PDUFA action date of October 2018.
Nov 17: Filed in EU via centralised procedure .·
Trial or other data
Jul 17: Safety and efficacy data announched from PIII DRIVE-AHEAD trial (NCT02403674; MK-1439A-021; EudraCT2014-003382-17) in treatment-naive pts with HIV-1 infections. The trial consists of a 96-week double-blind treatment period (base study) and an open label extension after completion of the base study. The randomised, double-blinded, parallel trial is recruiting 680 treatment naive pts in the US, Australia, Puerto Rico and the Netherlands. The trial achieved its primary safety and efficacy endpoints. After 48 weeks of treatment, 84% of the 364 pts taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81% of the 364 pts taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5% (95% CI: -2.0, 9.0). Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1 (95%CI: -16.1, 36.3). Comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69% in the DOR/3TC/TDF group and 73% in the EFV/FTC/TDF group. Of those pts with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81% in the DOR/3TC/TDF group and 81% in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0% (95% CI; -12.4, 14.3). The study achieved primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8% versus 37.1%, p <0.001); sleep disorders and disturbances (12.1% versus 25.5%, p <0.001); and inability to think clearly or concentrate (4.4% versus 8.2%, p = 0.033). The reported rates of drug-related adverse events were lower in the group taking DOR/3TC/TDF (31%) versus the group taking EFV/FTC/TDF (63%), representing a -31.9% treatment difference (95% CI: -38.6, -24.8). Treatment discontinuations due to adverse events for DOR/3TC/TDF and EFV/FTC/TDF were 3% and 7%, respectively. The most commonly reported adverse events occurring in ≥10% of pts in the DOR/3TC/TDF group compared with the EFV/FTC/TDF group were, headache (13% versus 12%); diarrhoea (11% versus 14%); nasopharyngitis (11% versus 9%); dizziness (9% versus 37%); nausea (8% versus 11%); abnormal dreams (5% versus 12%) and, rash (5% versus 12%), respectively. Treatment-emergent viral mutations causing drug-associated resistance was detected in 1.6% of pts in the group receiving DOR/3TC/TDF, and 3.3% of those in the EFV/FTC/TDF group, respectively, through Week 48.
Jun 15: Merck initiates the PIII DRIVE-SHIFT study to assess the safety and efficacy of doravirine/lamivudine/tenofovir disoproxil fumarate (100/300/300mg) in patients with HIV-1 infections, who were virologically suppressed on a regimen containing ritonavir-boosted protease inhibitor and two nucleoside reverse transcriptase inhibitors (NCT02397096). 660 patients will be recruited in the US. Collection of primary outcome data is expected to complete Mar 18 .·