Positive interim results have been reported from the pivotal phase 3 ONCEMRK trial, which is evaluating an investigational formulation of raltegravir (Isentress, Merck), given as two times 600 mg (1,200 mg) once-daily, for previously untreated adults with human immunodeficiency virus-1 (HIV-1) infection. The study met its primary efficacy endpoint: raltegravir 1,200 mg was noninferior to the approved dose of 400 mg twice-daily, each administered in combination with emtricitabine/tenofovir (Truvada, Gilead), as assessed by the proportion of patients achieving less than 40 copies/mL of HIV-1 RNA at week 48.
In addition, the secondary endpoints of tolerability and immunological efficacy (as measured by the change from baseline in CD4 cell counts at week 48) were comparable between the two treatment groups. The planned treatment duration is 96 weeks. Later this year, Merck plans to submit an application for licensure to the FDA for the new investigational formulation.
The newly formulated 600-mg tablet for once-daily use (two times 600 mg) being evaluated in this study is not approved for clinical use in the U.S., and the formulation is not interchangeable with the currently marketed 400-mg tablet.
Raltegravir is an integrase inhibitor for the treatment of HIV-1 infection as part of combination therapy in adult and pediatric patients 4 weeks of age and older and weighing at least 3 kg. Raltegravir works by inhibiting the insertion of HIV-1 DNA into human DNA by the integrase enzyme. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells.
Raltegravir is approved as part of combination therapy in 115 countries for the treatment of HIV-1 infection in adults. In addition, raltegravir, in combination therapy, has been approved for use in children and adolescents 2 years of age and older with HIV-1 infection in 64 countries.
In the U.S., raltegravir is indicated for use twice daily in combination with other antiretroviral agents for the treatment of HIV-1 infection in patients 4 weeks of age and older. The use of other active agents with raltegravir is associated with a greater likelihood of a treatment response.
Raltegravir does not cure HIV-1 infection or acquired immune deficiency syndrome (AIDS). Severe, potentially life-threatening and fatal skin reactions have been reported. These include cases of Stevens-Johnson syndrome, hypersensitivity reactions, and toxic epidermal necrolysis. Immune reconstitution syndrome can also occur.
Source: Merck; February 22, 2016.