Merck, known as MSD outside the United States and Canada, announced top-line results from the company’s phase 3 pivotal trial, ONCEMRK. ONCEMRK is evaluating an investigational once-daily formulation of Isentress (raltegravir), known as raltegravir 600 mg (to be given as 2 x 600 mg once-daily), for previously untreated HIV-1 infected adults.
The study met its primary efficacy endpoint: 1200 mg raltegravir (given as 2 x 600 mg once-daily) was statistically non-inferior to the marketed formulation approved dose of Isentress 400 mg twice-daily, each in combination therapy with Truvada, as assessed by the proportion of patients achieving HIV-1 RNA <40 copies/ml at week 48.
In addition, the secondary endpoints of tolerability and immunologic efficacy (as measured by change from baseline in CD4 cell counts at week 48) were comparable. Later this year, Merck plans to present detailed findings of the study at an upcoming scientific conference, and to submit applications for licensure to the US Food and Drug Administration and the European Medicines Agency for this investigational new formulation.
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.
“Merck has never wavered in our commitment to develop meaningful therapeutic options for people with HIV-1 infection,” said Dr. Eliav Barr, vice president clinical development, infectious diseases, Merck Research Laboratories. "We are pleased that this study has met its primary endpoint and look forward to presenting the data at a future congress.”
The ongoing phase 3 multicenter, double-blind, randomized, active comparator-controlled clinical trial is evaluating the efficacy and safety of raltegravir 1200 mg (given as 2 x 600 mg) once-daily compared to Isentress 400 mg twice-daily each in combination therapy with Truvada in previously untreated HIV-1 infected adult patients. The primary efficacy objective is the proportion of patients achieving HIV RNA <40 copies/ml at week 48. Secondary objectives included change from baseline in CD4 cell counts and tolerability at week 48. The newly formulated 600 mg tablet for once-daily use (2 x 600 mg), in this study, is not currently approved for use and this formulation is not interchangeable with the currently marketed 400 mg tablet.
The planned total treatment duration for this study is 96 weeks. Severe, potentially life-threatening and fatal skin reactions have been reported. This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction and toxic epidermal necrolysis.
The most commonly reported (=2 per cent) drug-related clinical adverse reactions of moderate to severe intensity in treatment-naïve adult patients receiving Isentress compared with efavirenz were insomnia (4 per cent vs 4 per cent), headache (4 per cent vs 5 per cent), nausea (3 per cent vs 4 per cent), fatigue (2 per cent vs 3 per cent), and dizziness (2 per cent vs 6 per cent) respectively. In treatment-experienced adult patients receiving Isentress, the most commonly reported (=2 per cent) drug-related clinical adverse reactions of moderate to severe intensity and at a higher incidence compared with placebo was headache (2 per cent vs <1 per cent). In both studies, intensities were defined as: Moderate (discomfort enough to cause interference with usual activity); or Severe (incapacitating with inability to work or do usual activity). In treatment-experienced pediatric patients 4 weeks through 18 years of age receiving Isentress, the frequency, type and severity of drug-related adverse reactions were comparable to those observed in adults.
Grade 2-4 creatine kinase laboratory abnormalities were observed in subjects treated with Isentress. Myopathy and rhabdomyolysis have been reported.
Isentress is Merck's integrase inhibitor for the treatment of HIV-1 infection in adult and paediatric patients ages four weeks and older and weighing at least 3 kg as part of combination HIV therapy. Isentress works by inhibiting the insertion of HIV-1 DNA into human DNA by the integrase enzyme and has demonstrated rapid antiviral activity. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells.
Isentress is approved as part of combination therapy in 115 countries for treatment of HIV-1 infection in adult patients. Isentress, in combination therapy, for use in children and adolescents with HIV-1 ages two years and older has also been approved for use in 64 countries, and Isentress oral suspension for infants at least four weeks of age is approved for use in 34 countries.