Edurant™ 96-Week Phase 3 safety and efficacy data presented

Janssen Therapeutics, Division of Janssen Products, LP, presented today 96-week findings from two pivotal Phase 3 clinical trials, known as ECHO and THRIVE, comparing the efficacy, safety and virology profile of its non-nucleoside reverse transcriptase inhibitor (NNRTI) EDURANT™ (rilpivirine) tablets versus efavirenz (EFV) in antiretroviral treatment-naïve, HIV-1-infected adults. The pooled analysis at 96 weeks showed that 78 percent of patients achieved and sustained an undetectable plasma viral load (HIV-1 RNA less than 50 copies/mL) while taking EDURANT as part of combination therapy. These findings were presented today at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Rome, Italy.

Pooled ECHO and THRIVE results for EDURANT and EFV, each administered once daily with a nucleoside/nucleotide background regimen in treatment-naïve, HIV-1-infected adults, showed that 78 percent of patients in both the EDURANT arm (n=686) and the EFV arm (n=682) reached an undetectable viral load at 96 weeks. These data demonstrated non-inferiority (12 percent margin) of EDURANT to EFV in lowering viral load in this population at 96 weeks, consistent with the 48-week primary analysis. Patients taking EDURANT had a virologic failure rate of 14 percent compared to 8 percent experienced by patients taking EFV, of which 3 percent and 2 percent occurred in the second year of treatment, respectively. Upon virologic failure, the emergence of resistance and cross-resistance to the NNRTI class was higher in the EDURANT arm compared to the EFV arm.

Finding safe and tolerable regimens over an extended period of time is so important in HIV care, and it is encouraging to see that the 96-week data for EDURANT remain fairly consistent with what we have seen previously,” said Calvin J. Cohen, M.D., M.Sc., lead clinical investigator of EDURANT Phase 3 trials and Research Director at Community Research Initiative of New England and Harvard Vanguard Medical Associates. “EDURANT remains an important new option for treatment-naïve patients and their physicians.”

Adverse events (AEs) leading to discontinuation in the EDURANT arm were 4 percent compared to 9 percent in the EFV arm, and there were no new safety concerns with either NNRTI between 48 and 96 weeks. The most common AEs of interest (all grades) reported in the EDURANT arm vs. the EFV arm at week 96 included dizziness (8 percent vs. 27 percent), abnormal dreams/nightmares (8 percent vs. 13 percent) and rash (4 percent vs. 15 percent). The incidence of Grade 2-4 AEs at least possibly related to treatment over at least 96 weeks was 17 percent in the EDURANT arm vs. 33 percent in the EFV arm.

EDURANT was approved in May 2011 by the US Food and Drug Administration (FDA) in combination with other antiretroviral (ARV) medications for treatment of adults with HIV infection who are new to ARV therapy. EDURANT is the third anti-HIV medication to be commercialized by Janssen Therapeutics in the US. An application for approval has also been submitted to the European Medicines Agency and elsewhere, including Canada, Switzerland and Australia.

About the Clinical Trials: ECHO and THRIVE

The Phase 3 trials evaluated the efficacy and safety of EDURANT in 1,368 antiretroviral treatment-naïve HIV-1-infected adults with plasma HIV-1 RNA greater than or equal to 5000 copies/mL. These studies — ECHO (Efficacy Comparison in treatment-naïve HIV-infected subjects Of TMC278 and efavirenz, or TMC278-C209) and THRIVE (TMC278 against HIV, in a once-daily RegImen Versus Efavirenz, or TMC278-C215) — were identical in design, with the exception of the background regimen (BR). The 1,368 patients in ECHO and THRIVE received either EDURANT (25 mg once daily) plus BR (n=686) or efavirenz (600 mg once daily) plus BR (n=682).

In TMC278‑C209, the BR was fixed to the specific nucleos(t)ide reverse transcriptase inhibitors (N(t)RTIs), tenofovir disoproxil fumarate plus emtricitabine. In TMC278‑C215, the BR consisted of two investigator-selected N(t)RTIs, tenofovir disoproxil fumarate plus emtricitabine or zidovudine plus lamivudine or abacavir plus lamivudine.

EDURANT Indication

EDURANT is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment‑naïve adult patients.

This indication is based on Week 48 safety and efficacy analyses from two randomized, double-blinded, active controlled, Phase 3 trials in treatment-naïve patients and Week 96 safety and efficacy analyses from a Phase 2b trial in treatment-naïve patients.

The following points should be considered when initiating therapy with EDURANT:

• More EDURANT treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure compared to subjects with HIV-1 RNA less than 100,000 copies/mL at the start of therapy.
• The observed virologic failure rate in EDURANT treated subjects conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz.
• More subjects treated with EDURANT developed lamivudine/emtricitabine associated resistance compared to efavirenz.

EDURANT does not cure HIV infection. Patients must stay on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses.

EDURANT Important Safety Information

Drug Interactions

• Coadministration of EDURANT with the following drugs is contraindicated because significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance and cross-resistance: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, proton pump inhibitors such as esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole, systemic dexamethasone, and products containing St. John’s wort (Hypericum perforatum). EDURANT should be used with caution when co administered with drugs that may reduce the exposure of rilpivirine
• EDURANT should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes
• EDURANT should not be used in combination with NNRTIs

This is not a complete list of potential drug interactions. Please see full Prescribing Information for more details.

Warnings and Precautions

• Depressive Disorders: Severe depressive disorders, defined as depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, and suicidal ideation, have been reported with EDURANT. Immediate medical evaluation is recommended for severe depressive symptoms
• Fat Redistribution: Redistribution and/or accumulation of body fat have been observed in patients receiving antiretroviral (ARV) therapy. The causal relationship, mechanism, and long-term consequences of these events have not been established
• Immune Reconstitution Syndrome has been reported in patients treated with combination ARV therapy, including EDURANT

Use in Specific Populations

• Hepatic Impairment: EDURANT should be used with caution in patients with severe hepatic impairment (Child-Pugh Class C) as pharmacokinetics of EDURANT have not been evaluated in these patients
• Pregnancy Category B: EDURANT should be used during pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnant women

Adverse Reactions

• The most common adverse drug reactions reported (incidence >2%) of at least moderate intensity (greater than or equal to Grade 2) in patients taking EDURANT through 48 weeks were depressive disorders (4%), insomnia (3%), headache (3%), and rash (3%)

Please see full Prescribing Information for more details available at:

http://www.edurant-info.com/sites/default/files/EDURANT-PI.pdf

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.