Gilead Sciences, Inc. announced that two phase 3b switch studies evaluating Odefsey (emtricitabine 200mg/rilpivirine 25mg/tenofovir alafenamide 25mg) for the treatment of HIV-1 infection met their primary objectives. The ongoing studies were designed to explore the efficacy and safety of Odefsey among virologically suppressed adult patients switching from the tenofovir disoproxil fumarate (TDF)-based regimens Complera (emtricitabine 200mg/rilpivirine 25mg/tenofovir disoproxil fumarate 300mg) (Study 1216) or Atripla (efavirenz 600mg/emtricitabine 200mg/tenofovir disoproxil fumarate 300mg) (Study 1160). Odefsey combines Gilead's emtricitabine and tenofovir alafenamide with rilpivirine, marketed by Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Odefsey maintained similar rates of virologic suppression as the TDF-based regimens in both studies based on the proportion of patients with HIV-1 RNA levels (viral load) <50 copies/ml. At week 48, virologic suppression was maintained in 94 percent of patients taking Odefsey and in 94 percent of patients taking Complera in Study 1216 (difference: -0.3 percent; 95 percent CI: -4.2 percent to +3.7 percent), and in 90 percent of patients taking Odefsey versus 92 percent of patients taking Atripla in Study 1160 (difference: -2.0 percent; 95 percent CI: -5.9 percent to +1.8 percent).
Compared to the TDF-based regimens, Odefsey demonstrated statistically significant improvements in bone mineral density (BMD) at the hip and spine (p<0.001) in both studies. Additionally, improvements in total and tubular proteinuria statistically favored Odefsey in both studies (p<0.001). Study regimens were generally well tolerated, and general safety and discontinuation rates due to adverse events were comparable in the two studies. The most commonly reported adverse events for Odefsey included upper respiratory tract infection, diarrhea, nasopharyngitis, cough and headache. Gilead plans to submit these data for presentation at scientific conferences in 2016.
"As people are living longer with HIV, there is an increasing need for safe and tolerable treatment options to help address the long-term health needs of people living with HIV," said Norbert Bischofberger, PhD, executive vice president, research and development and chief scientific officer, Gilead Sciences. "Results from these two studies support the efficacy, as well as the renal and bone safety profile, of Odefsey as a new treatment option for virologically suppressed patients."
Odefsey was approved in the United States on March 1, 2016, and is indicated as a complete regimen for the treatment of HIV-1 infection in patients 12 years of age and older who have no antiretroviral treatment history and HIV-1 RNA levels =100,000 copies/mL. Odefsey is also indicated as replacement for a stable antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/ml) for at least six months with no history of treatment failure and no known resistance to the individual components of Odefsey. No dosage adjustment of Odefsey is required in patients with estimated creatinine clearance =30 mL per minute.
Odefsey has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis, and post treatment acute exacerbation of hepatitis B.
Study 1216 is a phase 3b, randomized, double-blind, multicenter study among 630 virologically suppressed adults (HIV-1 RNA levels <50 copies/ml) on a stable regimen of Complera for = six consecutive months. Patients were randomized 1:1 to either maintain their Complera regimen or switch to Odefsey. Study 1160 is a phase 3b, randomized, double-blind, multicenter study among 875 virologically suppressed adults (HIV-1 RNA levels <50 copies/ml) on a stable regimen of Atripla for = six consecutive months. Patients were randomized 1:1 to either maintain their Atripla regimen or switch to Odefsey. The studies will follow patients for 96 weeks after randomization.
The studies are ongoing. The primary objective of each study is to evaluate the efficacy of switching from Complera or Atripla to Odefsey in HIV-1 positive subjects who are virologically suppressed as determined by the proportion of subjects with HIV-1 RNA <50 copies/ml at week 48 as defined by the FDA snapshot algorithm. The secondary objectives are to evaluate the bone safety of the regimens by the percent change from baseline in hip and spine BMD at week 48 and week 96, to evaluate the safety and tolerability of the treatment arms through week 48 and to evaluate the efficacy, safety and tolerability of the treatment arms through week 96.