STUDY DESIGN: VIROLOGICALLY SUPPRESSED ADULTS

Clinical trials of adults who switched to ODEFSEY® from Atripla®* or Complera®


Study 1160: Study design and baseline characteristics1,2

Study 1160: Phase 3b, randomized, double-blind, multicenter, international, non-inferiority study1,2

Primary endpoint2
Proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 using the FDA snapshot algorithm, with a prespecified non-inferiority margin of 8%


Selected secondary endpoints2
Percent change from baseline in hip and spine bone mineral density (BMD) at Week 48


  • Stable virologic suppression for at least 6 months and no documented resistance to FTC, TAF, or RPV were required for study inclusion1
Study 1160: Selected baseline characteristics2,3
Switched to
ODEFSEY
(n=438)
Remained on
Atripla*
(n=437)
Median age, years (range) 49 (21-74) 48 (19-76)
Sex
Male (%) 85 89
Female (%) 15 11
Race/ethnicity
White (%) 66 67
Black (%) 27 28
Hispanic/Latino ethnicity (%) 18 18
Asian (%) 2 2
HIV-1 RNA <50 copies/mL (%) 98 99
Median CD4+ cell count, cells/µL (range) 673 (140-1862) 666 (156-1727)
Proteinuria by urine dipstick (any grade) (%) 6 8

Warnings and precautions

  • Skin and hypersensitivity reactions: Severe skin and hypersensitivity reactions have been reported with the use of rilpivirine-containing regimens, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). In rilpivirine (RPV) clinical trials, most rashes were Grades 1-2 and occurred in the first 4-6 weeks of treatment; Grades 2-4 rash occurred in 1% of subjects. Discontinue ODEFSEY immediately if severe skin or hypersensitivity reactions occur, including severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis, or eosinophilia. Monitor clinical status including laboratory parameters and initiate appropriate therapy.
  • Loss of virologic response due to drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during ODEFSEY therapy and monitor for adverse reactions.
  • Prolongation of QTc interval: RPV doses 3 and 12 times higher than the recommended dose can prolong the QTc interval. Consider alternatives to ODEFSEY in patients at higher risk for Torsade de Pointes or when coadministered with a drug with known risk of Torsade de Pointes.

Study 1216: Study design and baseline characteristics1,4

Study 1216: Phase 3b, randomized, double-blind, multicenter, international, non-inferiority study1,4

Primary endpoint4
Proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 using the FDA snapshot algorithm, with a prespecified non-inferiority margin of 8%


Selected secondary endpoints4
Percent change from baseline in hip and spine bone mineral density (BMD) at Week 48


  • Stable virologic suppression for at least 6 months and no documented resistance to FTC, TAF, or RPV were required for study inclusion1
Study 1216: Selected baseline characteristics3,4
Switched to
ODEFSEY
(n=316)
Remained on
Complera
(n=314)
Median age, years (range) 46 (23-72) 44 (23-71)
Sex
Male (%) 87 92
Female (%) 13 8
Race/ethnicity
White (%) 75 75
Black (%) 21 17
Hispanic/Latino ethnicity (%) 13 17
Asian (%) 2 5
HIV-1 RNA <50 copies/mL (%) 97 99
Median CD4+ cell count, cells/µL (range) 673 (104-
2527)
668 (186-
1807)
Proteinuria by urine dipstick (any grades) (%) 10 9

Important Safety Information

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • ODEFSEY® is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of ODEFSEY have not been established in patients coinfected with HIV-1 and HBV. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of ODEFSEY. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue ODEFSEY. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Contraindications

  • Coadministration: Do not use with the following drugs, as coadministration may lead to loss of efficacy and possible resistance to ODEFSEY or the NNRTI class: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, proton pump inhibitors (e.g., dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole), systemic dexamethasone (>1 dose), and St. John's wort.

Warnings and precautions

  • Skin and hypersensitivity reactions: Severe skin and hypersensitivity reactions have been reported with the use of rilpivirine-containing regimens, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). In rilpivirine (RPV) clinical trials, most rashes were Grades 1-2 and occurred in the first 4-6 weeks of treatment; Grades 2-4 rash occurred in 1% of subjects. Discontinue ODEFSEY immediately if severe skin or hypersensitivity reactions occur, including severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis, or eosinophilia. Monitor clinical status including laboratory parameters and initiate appropriate therapy.
  • Loss of virologic response due to drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during ODEFSEY therapy and monitor for adverse reactions.
  • Prolongation of QTc interval: RPV doses 3 and 12 times higher than the recommended dose can prolong the QTc interval. Consider alternatives to ODEFSEY in patients at higher risk for Torsade de Pointes or when coadministered with a drug with known risk of Torsade de Pointes.
  • Depressive disorders: Evaluate patients with severe depressive symptoms to assess if symptoms are due to ODEFSEY and if the risks of continued treatment outweigh the benefits. In RPV adult clinical trials (N=686), the incidence of depressive disorders was 9%, Grades 3-4 depressive disorders was 1%, discontinuation due to depressive disorders was 1%, and suicidal ideation and suicide attempt was reported in 4 and 2 subjects, respectively. In an RPV adolescent clinical trial (N=36), the incidence of depressive disorders was 19%, Grades 3-4 depressive disorders was 6%, and suicidal ideation and suicide attempt were reported in 1 subject.
  • Hepatotoxicity: Hepatic adverse events have been reported, including cases of hepatic toxicity, in patients without pre-existing hepatic disease or other identifiable risk factors. In patients with hepatic abnormalities (e.g., hepatitis, elevated liver-associated tests), order laboratory tests before starting treatment and monitor for hepatotoxicity during treatment; consider testing and monitoring in all patients.
  • Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.
  • New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of FTC and tenofovir alafenamide (TAF) with elvitegravir and cobicistat, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not initiate ODEFSEY in patients with estimated creatinine clearance (CrCl) <30 mL/min. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue ODEFSEY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
    Renal monitoring: In all patients, monitor serum creatinine (SCr), serum phosphorus, CrCl, urine glucose, and urine protein prior to initiating ODEFSEY and during therapy, as clinically appropriate.
  • Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue ODEFSEY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse reactions

  • Most common adverse reactions with ODEFSEY (incidence ≥2%, all Grades) are headache (2%) and sleep disturbance (2%).

Drug interactions

  • Prescribing information: Consult the full prescribing information for ODEFSEY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments.
  • Metabolism: Drugs that induce CYP3A or P-gp and drugs that increase gastric pH can decrease the concentrations of components of ODEFSEY. Drugs that inhibit CYP3A or P-gp can increase the concentrations of components of ODEFSEY.
  • QT prolonging drugs: Consider alternatives to ODEFSEY in patients taking a drug with known risk of Torsade de Pointes.
  • Drugs affecting renal function: Coadministration of ODEFSEY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.

Dosage and administration

  • Dosage: Patients 12 years and older who weigh ≥35 kg: 1 tablet taken orally once daily with a meal.
  • Renal impairment: Not recommended in patients with CrCl <30 mL/min.
  • Testing prior to initiation: Test patients for HBV infection and assess SCr, serum phosphorus, CrCl, urine glucose, and urine protein.
  • Testing after initiation: In virologically-suppressed patients, additional monitoring of HIV-1 RNA and regimen tolerability is recommended.

Pregnancy and lactation

  • Pregnancy: There are insufficient human data on the use of ODEFSEY during pregnancy. An Antiretroviral Pregnancy Registry (APR) has been established; available data from the APR for FTC and RPV show no difference in the rates of birth defects compared with a US reference population.
  • Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.

Indication

ODEFSEY is indicated as a complete regimen for the treatment of HIV-1 infection in patients 12 years and older who have no antiretroviral (ARV) treatment history with HIV-1 RNA ≤100,000 copies/mL; or to replace a stable ARV regimen in patients who are virologically-suppressed (HIV-1 RNA <50 copies/mL) for ≥6 months with no history of treatment failure and no known resistance to any component of ODEFSEY.

View full Prescribing Information for ODEFSEY® and DESCOVY®, including BOXED WARNINGS.

*Atripla: efavirenz/emtricitabine/tenofovir disoproxil fumarate.
Complera: rilpivirine/emtricitabine/tenofovir disoproxil fumarate.

eGFRCG, estimated glomerular filtration rate (Cockcroft-Gault); QD, once daily.

References:

  1. ODEFSEY [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2017.
  2. DeJesus E, Ramgopal M, Crofoot G, et al. Switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study. Lancet HIV. 2017;4(5):e205-e213.
  3. Data on file. Gilead Sciences, Inc.
  4. Orkin C, DeJesus E, Ramgopal M, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study. Lancet HIV. 2017;4(5):e195-e204.