FDA Approves Isentress HD, in Combination With Other Antiretroviral Agents, for the Treatment of HIV-1 Infection

Integrase inhibitor is administered once daily

The FDA has given the nod to Isentress HD (Merck), a new 1,200-mg once-daily dose of the company’s integrase inhibitor raltegravir (Isentress), to be administered orally as two 600-mg film-coated tablets, with or without food, in combination with other antiretroviral agents for the treatment of human immunodeficiency virus 1 (HIV-1) infection in adults, and in pediatric patients weighing at least 40 kg, who are treatment-naïve or whose virus has been suppressed by an initial regimen of Isentress 400 mg twice daily.

The FDA’s decision was based on data from the pivotal phase 3 ONCEMRK trial. At week 48, 89% of 531 treatment-naïve HIV-1 infected patients receiving Isentress HD 1,200 mg (two 600-mg tablets) once a day achieved viral suppression of HIV-1 RNA to less than 40 copies/mL compared with 88% of 266 patients receiving Isentress 400 mg twice daily, each in combination therapy with emtricitabine plus tenofovir disoproxil fumarate, for a treatment difference of 0.5%.This finding was consistent in a variety of patient populations, including those with high viral loads (HIV-1 RNA greater than 100,000 copies/mL).

During 48 weeks of treatment, the rates of discontinuation of therapy due to adverse events were low (1% among patients receiving Isentress HD 1,200 mg once daily and 2% among patients receiving Isentress 400 mg twice daily). Clinical adverse events of all intensities (mild, moderate, and severe) occurring in 2% or more of patients treated with Isentress HD or Isentress included abdominal pain, diarrhea, vomiting, and decreased appetite. Treatment-emergent viral mutations leading to drug resistance were detected in less than 1% (4/531) of the patients treated with Isentress HD once daily.

Approved in 2007, raltegravir was the first integrase inhibitor developed for the treatment of patients with HIV-1 infection. Raltegravir is one of the regimen options recommended by the Department of Health and Human Services––in combination with other antiretroviral agents––as a first-line therapy in treatment-naïve HIV-1–infected adults. Raltegravir chewable tablets and oral suspension, each in combination therapy, are approved to treat pediatric patients at least four weeks of age and weighing less than 20 kg.

Raltegravir 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 and Isentress HD do not cure HIV-1 infection or acquired immune deficiency syndrome (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.

Source: Merck, May 30, 2017.