FDA Approves EDURANT(TM) (rilpivirine, TMC-278) for Use in Treatment-Naive Adults With HIV-1 Friday, May 20, 2011
Third medication for Tibotec Therapeutics HIV treatment portfolio |
TITUSVILLE, N.J., May 20, 2011 - The US Food and Drug Administration (FDA) today approved EDURANT(TM)(rilpivirine) tabletsfor use in combination with other antiretroviral agents (ARVs) in the treatment of human immunodeficiency virus type 1 (HIV-1) in adults who have never taken HIV therapy (treatment-naive).
EDURANT (pronounced ee' dur ant) was developed as TMC278 (rilpivirine) by Tibotec Pharmaceuticals and is a non-nucleoside reverse transcriptase inhibitor, or NNRTI. In HIV treatment, NNRTIs are one class of the several types of ARVs that combat replication of the virus(1); NNRTIs block a specific protein that HIV-1 uses for replication.(1)
EDURANT is the third anti-HIV medication to be commercialized in the United States by Tibotec Therapeutics, a division of Centocor Ortho Biotech Products, L.P.
"The complexity of HIV care can be especially challenging for people who have never before been treated, so the goal is to find a regimen that is effective and tolerable," 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. "In the pooled analysis of Phase 3 trials, EDURANT demonstrated efficacy and safety. During the first year, 2 percent of study participants discontinued treatment with EDURANT due to adverse drug reactions. This suggests EDURANT may provide a welcome new option for treatment-naive patients and their physicians."
The full indication is as follows:
EDURANT is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatmentnaive 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-naive patients and Week 96 safety and efficacy analyses from a Phase 2b trial treatment-naive 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.
The recommended oral dose of EDURANT tablets is one 25 mg tablet taken once daily with a meal.
The New Drug Application (NDA) submitted by Tibotec Pharmaceuticals in July 2010 included 48-week data from two ongoing global Phase 3 double-blinded, active controlled, randomized studies. These data were presented in July 2010 at the 18th International AIDS Conference in Vienna, Austria. An application for approval also has been submitted to the European Agency for the Evaluation of Medicinal Products and elsewhere, including Canada, Switzerland and Australia.
"The approval of EDURANT is an important new option for the thousands of people diagnosed with HIV each year in the US," said Vanessa Broadhurst, president of Tibotec Therapeutics. "This approval demonstrates our ongoing commitment to serving the needs of people living with HIV - in just five years, Tibotec has introduced three novel HIV medications, expanding options for patients across the treatment spectrum."
About the Clinical Trials: ECHO and THRIVE
The approved indication is based on safety and efficacy analyses from Week 48 of two ongoing, randomized, double-blinded, active controlled, global Phase 3 trials, and Week 96 safety and efficacy analyses from a Phase 2b trial in treatment-naive patients.
The Phase 3 trials evaluated the efficacy and safety of EDURANT in 1,368 antiretroviral treatment-naive HIV-1-infected adults with plasma HIV-1 RNA greater than or equal to 5000 copies/mL. These studies - ECHO (Efficacy Comparison in treatment-naive 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).
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.
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.In the pooled analysis, demographics and baseline characteristics were balanced between both arms and randomization was stratified by screening viral load (the amount of virus in the blood) in both trials, and by nucleos(t)ide backbone in THRIVE. The median duration of exposure for patients in the EDURANT arm and efavirenz arm was 55.7 and 55.6 weeks, respectively.
In the 48-week pooled analysis, 83 percent of patients (n=686) taking EDURANT as part of combination therapy reached an undetectable viral load (less than 50 copies), compared with 80 percent of patients (n=682) in the efavirenz arm. The virologic failure rate was 13 percent in the EDURANT arm and 9 percent in the efavirenz arm. The virologic failure rates were similar in both groups when the baseline viral load was less than or equal to 100,000 copies/mL, but were higher in patients in the EDURANT arm who had higher baseline viral loads (> 100,000). Upon virologic failure, the emergence of resistance and cross-resistance to the NNRTI class was higher in the EDURANT treated subjects compared to the efavirenz arm.
The most common adverse drug reactions (ADRs) to EDURANT (incidence > 2 percent) of at least moderate-to-severe intensity (greater than or equal to Grade 2) were depressive disorders (4 percent), insomnia (3 percent), headache (3 percent) and rash (3 percent). The proportion of patients who discontinued treatment with EDURANT or efavirenz due to ADRs, regardless of severity, was 2 percent and 4 percent, respectively.
The most common ADRs leading to discontinuation were psychiatric disorders: 10 (1 percent) patients in the EDURANT arm and 15 (2 percent) patients in the efavirenz arm. Rash led to discontinuation in 1 (0.1 percent) patient in the EDURANT arm and 10 (1.5 percent) patients in the efavirenz arm.
EDURANT does not cure HIV infection. Patients must stay on continuous HIV therapy to control HIV infection and decrease HIV related illnesses.
Important Safety Information
Drug Interactions - Coadministration of EDURANT(TM) 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, lansoprozole, omeprazole, pantoprozole, and rabeprozole, 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(TM) should be used with caution when coadministered with drugs that may reduce the exposure of rilpivirine a drug with a known risk of Torsade de Pointes - EDURANT(TM) 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(TM). 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(TM)
Use in Specific Populations -
Hepatic Impairment: EDURANT(TM) should be used with caution in patients with severe hepatic impairment (Child-Pugh Class C) as pharmacokinetics of EDURANT(TM) have not been evaluated in these patients -
Pregnancy Category B: EDURANT(TM) 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 (>= Grade 2) in patients taking EDURANT(TM) through 48 weeks were depressive disorders (4%), insomnia (3%), headache (3%), and rash (3%)
Please see full Prescribing Information for more details available at:
You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
About Tibotec Pharmaceuticals
Tibotec Pharmaceuticals is a global pharmaceutical research and development company. The Company's main research and development facilities are in Beerse, Belgium, with offices in Titusville, New Jersey and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs and anti-infectives for diseases of high unmet medical need.
About Tibotec Therapeutics
Tibotec Therapeutics, a division of Centocor Ortho Biotech Products, L.P., headquartered in Titusville, New Jersey, is dedicated to delivering innovative virology therapeutics that help healthcare professionals address serious unmet needs in people living with HIV.
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(1)AIDS Info (U.S. Department of Health and Human Services). HIV and Its Treatment: What You Should Know. December 2009. Pages 6, 10.
SOURCE Tibotec Therapeutics