PIFELTRO and DELSTRIGO label updates

September 20, 2019 FDA approved updates to the PIFELTRO (doravirine) and DELSTRIGO (doravirine/lamivudine/tenofovir DF) product labeling to expand the indication to to include patients who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine or to the individual components of DELSTRIGO. The approval was based an open-label, randomized trial (DRIVE-SHIFT) in virologically suppressed (HIV-1 RNA < 50 copies/mL) HIV-1 infected subjects who were on their baseline regimen for at least 6 months prior to trial entry, with no history of virologic failure. Subjects were randomized to either switch to DELSTRIGO at baseline (n = 447, Immediate Switch Group (ISG)), or stay on their baseline regimen until Week 24, at which point they switched to DELSTRIGO (n = 223, Delayed Switch Group (DSG)). At baseline, the median age of subjects was 43 years, 16% were female, and 24% were Non-White, 21% were of Hispanic or Latino ethnicity, 3% had hepatitis B and/or C virus co-infection, 17% had a history of AIDS, 96% had CD4+ T-cell count greater than or equal to 200 cells/mm3, 70% were on a regimen containing a protease inhibitor (PI) plus ritonavir, 24% were on a regimen containing an non-nucleoside reverse transcriptase inhibitor (NNRTI), 6% were on a regimen containing elvitegravir plus cobicistat, and 1% were on a regimen containing a PI plus cobicistat; these characteristics were similar between treatment groups. The proportion of subjects with HIV-1 RNA > 50 copies/mL in the DELSTRIGO ISG group at Week 48 was 2% compared to 1% for the DSG at Week 24. The treatment difference and 95% CI is 0.7 (-1.3%,2.6%). The safety of DELSTRIGO in virologically-suppressed adults was based on Week 48 data from 670 subjects in the DRIVE-SHIFT trial. Overall, the safety profile in virologically-suppressed adult subjects was similar to that in subjects with no antiretroviral treatment history. Change in Lipids from Baseline Changes from baseline at Week 24 in LDL-cholesterol, non-HDL-cholesterol, total cholesterol, triglycerides, and HDL-cholesterol in subjects on a PI plus ritonavir-based regimen at baseline were evaluated. The LDL and non-HDL comparisons were pre-specified, and the differences were statistically significant, showing superiority for an immediate switch to DELSTRIGO for both parameters. The clinical benefit of these findings has not been demonstrated. Additionally, the “4-week cessation period is recommended prior to initiation of doravirine” for rifabutin was removed.

The updated labels will soon be available at Drugs@FDA or DailyMed Kimberly Struble Division of Antiviral Products Food and Drug Administration Elizabeth Thompson Division of Antiviral Products Food and Drug Administration Michael Stanfield Jr. Division of Antiviral Products Food and Drug Administration