FDA News

FDA approves once-daily Isentress regimen for treatment of HIV

Merck announced today that the FDA has approved Isentress HD — a new, once-daily, 1,200-mg dose of the company’s integrase inhibitor, Isentress — for the treatment of HIV.

Isentress HD (raltegravir) is approved for use in adults and pediatric patients weighing at least 40 kg who are either treatment naive or virally suppressed and received an initial regimen of 400 mg of raltegravir given twice daily, according to a press release. It is to be administered orally as two 600-mg tablets in combination with other antiretroviral agents.

Michael S. Saag
Michael S. Saag

“Insentress has been used as a component of treatment regimens for patients diagnosed with HIV-1 for almost a decade,” Michael S. Saag, MD, associate dean for global health and director of the Center for AIDS Research at the University of Alabama at Birmingham School of Medicine, said in the release. “The addition of a convenient once-daily version with a comparable efficacy and safety profile at 48 weeks to the existing twice-daily version of Isentress provides physicians with a new therapeutic option for some patients with HIV-1 infection.”

The approval of once-daily raltegravir is based on phase 3 data from the ONCEMRK trial, an ongoing multicenter, double-blind, randomized trial comparing the safety and efficacy of once-daily raltegravir (1,200 mg) with twice-daily raltegravir (400 mg), each in combination with Truvada (emtricitabine/tenofovir disoproxil fumarate; Gilead Sciences) in treatment-naive patients with HIV.

At week 48, 89% (n = 531) patients receiving the once-daily regimen achieved viral suppression compared with 88% (n = 266) of patients receiving the twice-daily regimen, yielding a 0.5% (95% CI, –4.2 to 5.2) difference in treatment, according to the release. The results were similar across demographic groups and a variety of populations, including those with a high viral load (HIV-1 RNA > 100,000 copies/mL).

Researchers detected treatment-emergent viral mutations leading to drug resistance in less than 1% of patients who received the once-daily regimen. The rate of discontinuation due to adverse events was 1% among patients receiving the once-daily regimen and 2% among those receiving the twice-daily regimen. Clinical adverse events in both study arms included abdominal pain, diarrhea, vomiting and decreased appetite. Drug-related moderate to severe adverse reactions occurred in less than 2% of the cohort. However, severe, potentially life-threatening and fatal skin reactions were reported, including cases of Stevens-Johnson syndrome, hypersensitivity reaction and toxic epidermal necrolysis.

“Immediately discontinue treatment with Isentress or Isentress HD and other suspect agents if severe hypersensitivity, severe rash or rash with systemic symptoms or liver aminotransferase elevations develop and monitor clinical status, including liver aminotransferases closely,” the release said.

Raltegravir HD can be administered with a wide range of other agents. However, it is not recommended to be administered in combination with aluminum and/or magnesium-containing antacids, calcium carbonate antacids, rifampin, Aptivus (tipranavir, Boehringer Ingelheim)/ritonavir, Intelence (etravirine, Janssen) and other strong inducers of metabolizing enzymes such as carbamazepine, phenobarbital and phenytoin.

“Because of improvements in the effectiveness of antiretroviral therapies and with appropriate access to care, HIV infection can now be managed as a chronic disease,” Carl Schmid, deputy director of the AIDS Institute, said in the release. “For people living with HIV, having a wide range of effective therapies is important because it provides options to fit patients’ individual needs and lifestyles.”

Disclosure: Infectious Disease News was unable to confirm relevant financial disclosures at the time of publication.

 

Merck announced today that the FDA has approved Isentress HD — a new, once-daily, 1,200-mg dose of the company’s integrase inhibitor, Isentress — for the treatment of HIV.

Isentress HD (raltegravir) is approved for use in adults and pediatric patients weighing at least 40 kg who are either treatment naive or virally suppressed and received an initial regimen of 400 mg of raltegravir given twice daily, according to a press release. It is to be administered orally as two 600-mg tablets in combination with other antiretroviral agents.

Michael S. Saag
Michael S. Saag

“Insentress has been used as a component of treatment regimens for patients diagnosed with HIV-1 for almost a decade,” Michael S. Saag, MD, associate dean for global health and director of the Center for AIDS Research at the University of Alabama at Birmingham School of Medicine, said in the release. “The addition of a convenient once-daily version with a comparable efficacy and safety profile at 48 weeks to the existing twice-daily version of Isentress provides physicians with a new therapeutic option for some patients with HIV-1 infection.”

The approval of once-daily raltegravir is based on phase 3 data from the ONCEMRK trial, an ongoing multicenter, double-blind, randomized trial comparing the safety and efficacy of once-daily raltegravir (1,200 mg) with twice-daily raltegravir (400 mg), each in combination with Truvada (emtricitabine/tenofovir disoproxil fumarate; Gilead Sciences) in treatment-naive patients with HIV.

At week 48, 89% (n = 531) patients receiving the once-daily regimen achieved viral suppression compared with 88% (n = 266) of patients receiving the twice-daily regimen, yielding a 0.5% (95% CI, –4.2 to 5.2) difference in treatment, according to the release. The results were similar across demographic groups and a variety of populations, including those with a high viral load (HIV-1 RNA > 100,000 copies/mL).

Researchers detected treatment-emergent viral mutations leading to drug resistance in less than 1% of patients who received the once-daily regimen. The rate of discontinuation due to adverse events was 1% among patients receiving the once-daily regimen and 2% among those receiving the twice-daily regimen. Clinical adverse events in both study arms included abdominal pain, diarrhea, vomiting and decreased appetite. Drug-related moderate to severe adverse reactions occurred in less than 2% of the cohort. However, severe, potentially life-threatening and fatal skin reactions were reported, including cases of Stevens-Johnson syndrome, hypersensitivity reaction and toxic epidermal necrolysis.

“Immediately discontinue treatment with Isentress or Isentress HD and other suspect agents if severe hypersensitivity, severe rash or rash with systemic symptoms or liver aminotransferase elevations develop and monitor clinical status, including liver aminotransferases closely,” the release said.

Raltegravir HD can be administered with a wide range of other agents. However, it is not recommended to be administered in combination with aluminum and/or magnesium-containing antacids, calcium carbonate antacids, rifampin, Aptivus (tipranavir, Boehringer Ingelheim)/ritonavir, Intelence (etravirine, Janssen) and other strong inducers of metabolizing enzymes such as carbamazepine, phenobarbital and phenytoin.

“Because of improvements in the effectiveness of antiretroviral therapies and with appropriate access to care, HIV infection can now be managed as a chronic disease,” Carl Schmid, deputy director of the AIDS Institute, said in the release. “For people living with HIV, having a wide range of effective therapies is important because it provides options to fit patients’ individual needs and lifestyles.”

Disclosure: Infectious Disease News was unable to confirm relevant financial disclosures at the time of publication.