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On August 21, 2017, FDA approved changes to the Odefsey (emtricitabine/rilpivirine/tenofovir alafenamide) label to include data from 48 week data from trials in which subjects switched to Odefsey from tenofovir disoproxil fumarate based regimens (Complera (emtricitabine/rilpirivine/tenofovir disoproxil fumarate) or Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate)). The major changes to the label are summarized below. Section 6: Adverse Reactions was updated as follows:6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug (or a drug given in various combinations with other concomitant therapy) cannot be directly compared to rates in the clinical trials of another drug (or drug given in the same or different combination therapy) and may not reflect the rates observed in practice. Adverse Reactions in Clinical Trials of ODEFSEY in Virologically-Suppressed Adult Subjects with HIV-1 Infection The safety of ODEFSEY in virologically-suppressed adults is based on Week 48 data from two randomized, double-blinded, active-controlled clinical trials, 1160 and 1216, that enrolled 1505 adult subjects who were virologically-suppressed for at least 6 months. Both trials were designed to compare switching to ODEFSEY to maintaining efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) or emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) in Trials 1160 and 1216, respectively. A total of 754 subjects received one tablet of ODEFSEY daily [see Clinical Studies (14.1)]. Table 1 Adverse Reactionsa (All Grades) Reported in ≥1% of HIV-1 Infected Virologically-Suppressed Adults in Trial 1160 or Trial 1216 (Week 48 analysis)
a Frequencies of adverse reactions are based on all adverse events attributed to study drugs by the investigator. Renal Laboratory Tests In Trial 1216, the median baseline eGFR was104 mL per minute for subjects who switched to ODEFSEY from FTC/RPV/TDF (N=316) and the mean serum creatinine decreased by 0.02 mg per dL from baseline to Week 48. In Trial 1160, the median baseline eGFR was 110 mL per minute for subjects who switched to ODEFSEY from EFV/FTC/TDF (N=438), and the mean serum creatinine increased by 0.1 mg per dL from baseline to Week 48. Bone Mineral Density Effects Changes in BMD from baseline to Week 48 were assessed by dual-energy X-ray absorptiometry (DXA) in Trials 1216 and 1160. In Trial 1216, mean bone mineral density (BMD) increased in subjects who switched to ODEFSEY (1.61% lumbar spine, 1.04% total hip) and remained stable or decreased in subjects who remained on FTC/RPV/TDF (0.08% lumbar spine, −0.25% total hip). BMD declines of 5% or greater at the lumbar spine were experienced by 1.7% of ODEFSEY subjects and 3.0% of FTC/RPV/TDF subjects. BMD declines of 7% or greater at the femoral neck were experienced by 0% of ODEFSEY subjects and 1.2% of FTC/RPV/TDF subjects. In Trial 1160, mean BMD increased in subjects who switched to ODEFSEY (1.65% lumbar spine, 1.28% total hip) and decreased slightly in subjects who remained on EFV/FTC/TDF (−0.05% lumbar spine, −0.13% total hip). BMD declines of 5% or greater at the lumbar spine were experienced by 2.3% of ODEFSEY subjects and 4.9% of EFV/FTC/TDF subjects. BMD declines of 7% or greater at the femoral neck were experienced by 1.4% of ODEFSEY subjects and 3.3% of EFV/FTC/TDF subjects. The long-term clinical significance of these BMD changes is not known. Serum Lipids Changes from baseline in total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and total cholesterol to HDL ratio for Trials 1216 and 1160 are presented in Table 2. Table 2 Lipid Values, Mean Change from Baseline Reported in Subjects Receiving ODEFSEY, FTC/RPV/TDF and EFV/FTC/TDF in Trials 1216 and 1160 at 48 Weeks
a The change from baseline is the mean of within-subject changes from baseline for subjects with both baseline and Week 48 values. Section 12.4 Microbiology now includes the following ODEFSEY: Through Week 48, in subjects who switched to ODEFSEY from FTC/RPV/TDF or EFV/FTC/TDF (Trials 1216 (N=316) and 1160 (N=438), respectively), of seven subjects who developed virologic failure, three subjects had detectable NNRTI and/or NRTI resistance substititions at virologic failure that were pre-existing in the baseline sample by proviral DNA sequencing; one of these subjects resuppressed while maintaining ODEFSEY. The efficacy results from Trials 1216 and 1160 were included in Section 14: Clinical Studies 14 CLINICAL STUDIES14.1 Clinical Trial Results in HIV-1 Virologically-Suppressed Subjects Who Switched to ODEFSEY In Trial 1216, the efficacy and safety of switching from emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) to ODEFSEY were evaluated in a randomized, double-blind study of virologically-suppressed HIV-1 infected adults. Subjects were suppressed (HIV-1 RNA <50 copies/mL) on their baseline regimen of FTC/RPV/TDF for at least 6 months and have no documented resistance mutations to FTC, TAF, or RPV prior to study entry. Subjects were randomized in a 1:1 ratio to either switch to ODEFSEY (N=316) once daily or stay on FTC/RPV/TDF (N=314) once daily. Subjects had a mean age of 45 years (range: 23−72), 90% were male, 75% were White, and 19% were Black. The mean baseline CD4+ cell count was 709 cells/mm3 (range: 104−2527). In Trial 1160, the efficacy and safety of switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) to ODEFSEY were evaluated in a randomized, double-blind study of virologically-suppressed HIV-1 infected adults. Subjects must have been stably suppressed (HIV-1 RNA <50 copies/mL) on their baseline regimen of EFV/FTC/TDF for at least 6 months and have no documented resistance mutations to FTC, TAF, or RPV prior to study entry. Subjects were randomized in a 1:1 ratio to either switch to ODEFSEY (N=438) once daily or stay on EFV/FTC/TDF (N=437) once daily. Subjects had a mean age of 48 years (range: 19−76), 87% were male, 67% were White, and 27% were Black. The mean baseline CD4+ cell count was 700 cells/mm3 (range: 140−1862). Treatment outcomes of Trials 1216 and 1160 are presented in Table 11. Table 11 Virologic Outcomes of Trials 1216 and 1160 at Week 48a in Virologically-Suppressed Subjects who Switched to ODEFSEY
a Week 48 window was between Day 295 and 378 (inclusive). In addition, section 2.1 was updated to state, “It is recommended that serum creatinine, serum phosphorus, estimated creatinine clearance, urine glucose, and urine protein should be assessed before initiating ODEFSEY and during therapy in all patients as clinically appropriate.” Also velpatasvir was added to list of drugs without clinically significant interactions with Odefsey. The updated labels will soon be available drugs@fda or DailyMed Steve Morin Kimberly Struble Richard Klein For more information about the HIV Liaison Program visit the FDA Patient Network Subscriber Services:
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