Date: 2016-07-21
Type of information: Results
phase: 3b
Announcement: results
Company: Gilead Sciences (USA - CA)
Product: Odefsey®(emtricitabine 200mg/rilpivirine 25mg/tenofovir alafenamide 25mg)
Action
mechanism: reverse transcriptase inhibitor. All three substances act by inhibition of HIV-1 reverse transcriptase, an enzyme needed for replication of the virus; rilpivirine hydrochloride is a non-nucleoside reverse transcriptase. Emtricitabine and tenofovir alafenamide are substrates and competitive inhibitors of HIV reverse transcriptase. After phosphorylation, they are incorporated into the viral DNA chain, resulting in chain termination. Rilprivirine activity is mediated by non-competitive inhibition of HIV 1 reverse transcriptase. Emtricitabine and tenofovir alafenamide are from Gilead Sciences and rilpivirine is from Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen). The Odefsey® approval is part of an ongoing development and commercialization agreement between Gilead and Janssen, first established in 2009. Under this agreement, Gilead is responsible for the manufacturing, registration, distribution and commercialization of the product in most countries, while Janssen will distribute it in approximately 17 markets and have co-detailing rights in several key markets, including the United States . The original agreement was established for the development and commercialization of Complera®, marketed as Eviplera® in the European Union , and expanded in 2014 to include Odefsey. Odefsey® was approved in the United States on March 1, 2016 and in the EU on June 21, 2016.
Disease: HIV-1 infection
Therapeutic area: Infectious diseases
Country:
Trial
details: 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.
Latest
news: * On July 21, 2016, Gilead Sciences 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® 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.
