Bristol-Myers Squibb Company, Gilead Sciences, Inc. and Merck & Co., Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has issued a positive opinion on the Marketing Authorisation Application for Atripla (efavirenz 600mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 30 0 mg).
Specifically, the CHMP has recommended Atripla for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults with virologic suppression to HIV-1 RNA levels of < 50 copies/ml on their current combination antiretroviral therapy for more than three months. Patients must not have experienced virological failure on any prior antiretroviral therapy and must be known not to have harboured virus strains with mutations conferring significant resistance to any of the three components contained in Atripla prior to initiation of their first antiretroviral treatment regimen.
The CHMP's positive recommendation will be reviewed by the European Commission, which has the authority to approve medicinal products for use in the 27 countries of the European Union. The companies expect the European Commission to issue its decision on the marketing authorization for Atripla toward the end of the year. Once granted by the European Commission, Atripla would represent the first and only once-daily single tablet regimen for many HIV/AIDS patients in the European Union.
"Each of the components in Atripla has been shown to be effective and has a well-established tolerability profile in HIV patients. This first one-pill-a-day treatment for HIV represents a simplification of dosing, which is important as patients remain on therapy longer," said Brian Gazzard, MD, director, Clinical Research, Chelsea and Westminster Hospital, London.
Efavirenz is marketed by Bristol-Myers Squibb under the tradename Sustiva in the United States, Canada and six European countries (France, Germany, Republic of Ireland, Italy, Spain and the United Kingdom). In other territories, including all other countries of the European Union, efavirenz is commercialised by Merck & Co., Inc., (known as Merck Sharp & Dohme (MSD) in many countries outside of the United States) and is marketed in most of these countries under the tradename Stocrin. Emtricitabine and tenofovir disoproxil fumarate are commercialised by Gilead under the tradenames Emtriva and Viread, respectively, and are commonly prescribed together as a once-daily, fixed-dose tablet, marketed under the tradename Truvada for use as part of combination therapy.
The MAA for Atripla in the European Union was filed jointly by the three companies through a three-way joint venture based in Ireland called Bristol-Myers Squibb Gilead Sciences And Merck Sharp & Dohme Limited.
Atripla is currently the first and only once-daily single tablet regimen approved for the treatment of HIV-1 infection in adults in the United States for use either as stand-alone therapy or in combination with other antiretroviral agents. Atripla was approved by the US Food and Drug Administration (FDA) in July 2006 and has since become the most-prescribed treatment regimen for patients starting HIV therapy in the United States.
Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate [DF] 300 mg) is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.
Coadministration of Atripla with didanosine, atazanavir, astemizole, bepridil, cisapride, midazolam, pimozide, triazolam, ergot derivatives, or voriconazole is contraindicated.
Serious psychiatric adverse experiences, including severe depression (2.4per cent), suicidal ideation (0.7per cent), nonfatal suicide attempts (0.5per cent), aggressive behaviour (0.4per cent), paranoid reactions (0.4per cent), and manic reactions (0.2per cent), have been reported in patients receiving efavirenz. In addition to efavirenz, factors identified in a clinical study that were associated with an increase in psychiatric symptoms included a history of injection drug use, psychiatric history, and use of psychiatric medication. There have been occasional reports of suicide, delusions, and psychosis-like behaviour, but it could not be determined if efavirenz was the cause. Patients with serious psychiatric adverse experiences should be evaluated immediately to determine whether the risks of continued therapy outweigh the benefits.
Fifty-three per cent of patients reported central nervous system symptoms (including dizziness [28.1per cent], insomnia [16.3per cent], impaired concentration [8.3per cent], somnolence [7.0per cent], abnormal dreams [6.2per cent], and hallucinations [1.2per cent]) when taking efavirenz compared to 25per cent of patients receiving control regimens. These symptoms usually begin during Days 1-2 of therapy and generally resolve after the first 2-4 weeks of therapy; they were severe in 2.0per cent of patients, and 2.1per cent of patients discontinued therapy. After 4 weeks of therapy, the prevalence of nervous system symptoms of at least moderate severity ranged from 5per cent to 9per cent in patients treated with regimens containing efavirenz. Nervous system symptoms are not predictive of the less frequent psychiatric symptoms.
The FDA also granted approval of an alternate trade address of Atripla for developing countries, where Atripla is being made available as a white-coloured tablet to distinguish it from the salmon-coloured version currently available in the United States. In August 2006, Gilead and Merck established an agreement for distribution of the product in developing countries, and in March 2007, the World Health Organization added Atripla to its Model List of Essential Medicines.