Merck has announced efficacy and safety data in previously untreated adults with HIV-1 infection for the company’s investigational once-daily formulation of ISENTRESS® (raltegravir), known as raltegravir 600 mg (to be given as 2 x 600 mg), from the ongoing Phase 3 pivotal trial called ONCEMRK. The data evaluating efficacy and safety at 48 weeks of therapy were presented as a late-breaking abstract at the 21st International AIDS Conference (AIDS 2016) being held in Durban, South Africa, from July 18-22, 2016.
The study found that after 48 weeks of treatment, 1200 mg raltegravir (given as 2 x 600 mg once-daily) was statistically non-inferior (88.9 percent, 472/531) to the marketed formulation approved dose of ISENTRESS 400 mg twice-daily (88.3 percent, 235/266), each in combination therapy with TRUVADA®(emtricitabine/tenofovir disoproxil fumarate); with a treatment difference [95 percent confidence interval] of 0.5 (-4.2, 5.2), as assessed by the proportion of patients achieving less than 40 copies/mL of HIV RNA. Furthermore, the study showed comparable rates of reported drug-related clinical adverse events and rates of discontinuation between the two treatment groups.
ISENTRESS is indicated 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 ISENTRESS is associated with a greater likelihood of treatment response.
ISENTRESS (raltegravir) does not cure HIV-1 infection or AIDS. Severe, potentially life-threatening and fatal skin reactions have been reported. This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction and toxic epidermal necrolysis. Immediately discontinue treatment with ISENTRESS and other suspect agents if severe hypersensitivity, severe rash, or rash with systemic symptoms or liver aminotransferase elevations develops and monitor clinical status, including liver aminotransferases closely.
“It is important for patients living with HIV-1 to have additional therapeutic options for the treatment of HIV-1 infection to meet their diverse needs,” said Dr. Pedro Cahn, chief of the infectious disease unit at Juan A. Fernandez Hospital, Buenos Aires, Argentina, and lead study author. “This once-daily investigational formulation of raltegravir has the potential to simplify some HIV-1 infected patients’ regimens, which may be beneficial to those patients as they continue to manage their disease.”
The newly formulated 600 mg tablet for once-daily use (2 x 600 mg), used in the ONCEMRK study, is not currently approved for use and this formulation is not interchangeable with the currently marketed 400 mg tablet.
Based on these results from Week 48 of the ONCEMRK study, the European Medicines Agency (EMA) has accepted the file for the investigational once-daily formulation of ISENTRESS for review. Merck plans to submit applications for licensure in several countries, including the United States later this year.