Summary of evidence and Expert Committee recommendations
A new application for a new FDC medicine, tablets containing 600 mg efavirenz, 200 mg emtricitabine and 300 mg tenofovir, to be listed in section 6.4.2 Antiretrovirals, as a combination of NRTIs and NNRTIs has been submitted by Merck Sharp & Dohme, France.
The Committee received the letter from Merck as a late paper.
Efavirenz, tenofovir and emtricitabine are listed in current WHO treatment guidelines for adults (1) as one option for first-line combination treatment. As stated in the application, the triple combination has so far
been registered in the USA only, although other regulatory approvals are being sought.
The evidence for comparative effectiveness and safety in this application consisted of two studies: Study 934, published by Gallant et al. 2006 (2) and an observational study, ANRS 1207 in 40 subjects (presented as a poster only). Neither study used the proposed FDC. Gallant et al. compared treatment with the three components given separately with a FDC of AZT/ 3TC plus efavirenz, and the observational study appears to have used the individual components. Evidence of safety was based on the use of the components individually and in combination, not as an FDC, and is as presented in the other applications. Postmarketing safety reports from the use of the FDC were also provided but they reported adverse events only and were unquantified. Causality in relation to use of the FDC was not assessed. There was no evidence of use of this combination in resource poor settings. The Committee noted that differential pricing of the FDC is proposed through an access programme, although the details were not
provided in the application.
The Committee noted that this combination is one of several proposed in the WHO treatment guidelines, and is one combination for first-line treatment. The combination can be used in adult HIV patients but not children; efavirenz should not be used in pregnant women. It is specifically recommended for use in patients co-infected with HBV. One product of adequate quality exists, containing appropriate doses of the components and there has been one clinical study using the components of the FDC at the same doses and a small observational study using this FDC.
The Committee therefore decided this FDC should be added to the core list, noting particularly its utility in patients with HBV co-infection.
1. Antiretroviral therapy for HIV infection in adults and adolescents in resource limited settings: toward universal access. Recommendations for a public health approach – 2006 revision. Geneva, Switzerland, World Health Organization, 2006 (http://www.who.int/hiv/pub/guidelines/adult/en/index.html).
2. Gallant JE et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. New England Journal of Medicine, 2006, 354:251–260.