Odefsey Receives Approved Label Change from FDA

Changes include additional trial data in virologically-suppressed adults with HIV-1 infection.

The FDA approved changes to the Odefsey (emtricitabine/rilpivirine/tenofovir alafenamide) label to include updated data from clinical trials examining patients who switched from tenofovir disoproxil fumarate based-regimens to Odefsey.

Major changes to the label included adverse events (AEs), microbiology, and clinical trial results, according to an FDA press release.

The safety of Odefsey is based on week 48 data from clinical trials 1160 and 1216, which included 1505 adults with HIV-1 who were virologically suppressed for at least 6 months. Both trials compared switching to Odefsey to maintaining efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) or emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF). There were 754 participants who received an Odefsey tablet once-daily.

The most common AEs reported in at least 2% of patients in the Odefsey arms were headache and sleep disturbance. More than 98% of AEs in the Odefsey arm were of mild-to-moderate intensity, according to the release.

Two percent of patients who received Odefsey discontinued treatment due to AEs, regardless of severity, compared with 1% for FTC/RPV/TDF and 2% for EFV/FTC/TDF.

The median baseline glomerular filtration rate (eGFR) was 104 mL per minute for patients who switched from FTC/RPV/TDF to Odefsey in trial 1216. From baseline to week 48, the mean serum creatinine decreased by 0.02 mg per dL.

The median baseline eGFR in trial 1160 was 110 mL per minute for patients who switched from EFV/FTC/TDF to Odefsey. The mean serum creatinine increased by 0.1 mg per dL from baseline to week 48, according to the report.

In trial 1216, the mean bone mineral density (BMD) increased in patients who switched to Odefsey and remained stable or decreased for patients who remained on FTC/RPV/TDF.

BMD declines of 5% or greater at the lumbar spine were experienced by 1.7% of participants in the Odefsey arm and 3% in the FTC/RPV/TDF, according to the release. Declines of 7% or greater at the femoral neck were experienced by 0% of patients in the Odefsey arm and 1.2% in the FTC/RPV/TDF arm.

In trial 1160, the mean BMD increased in patients who switched to Odefsey and slightly decreased in participants who remained on EFV/FTC/TDF. According to the release, the long-term clinical significance of BMD changes is unknown.

Trial 1216 and Trial 1160 Details

The safety and efficacy of switching from FTC/RPV/TDF to Odefsey in trial 1216 were evaluated in a randomized, double-blind study of adults with virologically suppressive HIV-1. The participants were suppressed using the baseline regimen of FTC/RPV/TDF for at least 6 months, and have no reported resistance mutations to FTC, TAF, or RPV, prior to entering the study.

Ninety-percent of participants were male, with a mean age of 45 years. The mean baseline CD4+ cell count was 709 cells/mm3.

In trial 1160, investigators evaluated the safety and efficacy of switching from EFV/FTC/TDF to Odefsey in a randomized, double-blind study comprised of virologically suppressed HIV-1 infected adults. To be eligible for the study, participants were required to have been stably suppressed from EFV/FTC/TDF baseline regiment for at least 6 months, with no documented resistance mutations to FTC, TAF, or RPV prior to study entry. The mean baseline CD4+ cell count was 700 cells/mm3.

Section 2.1 was also 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.”