The pivotal phase 3 AMBER study regarding the safety and efficacy of the investigational darunavir-based single tablet HIV regimen has achieved its primary endpoint.
*Updated on 10/30/2017 at 1:57 PM EST
Janssen Pharmaceuticals has announced that their phase 3 AMBER study has achieved its primary endpoint, which focused on virologic response rate. The investigational darunavir-based single tablet regimen (STR) has proved to be “non-inferior” to darunavir/cobicistat (D/C) plus emtricitabine and tenofovir disoproxil fumarate (F/TDF) in HIV-1-positive adults without previous treatment.
The safety and efficacy results of the 48-week phase 3 “randomized, double-blind, active-controlled, international, multi-center, non-inferiority study” will be presented this week at the 16th European AIDS Conference, being held in Milan, Italy, according to the press release.
In a recent interview with Contagion®, Magda Opsomer, MD, director and clinical leader of Infectious Diseases and Vaccines at Janssen Pharmaceutical Companies, in Belgium, explained why darunavir may be more beneficial than other HIV medications.
“Darunavir is a boosted protease inhibitor,” she explained, “And, what is special about it is that it has a very high genetic barrier to the development of resistance. This is very important when it comes to treating patients, because, as we know, resistance makes it more difficult to treat patients at the end.”
"Initially, DRV was approved for treatment-experienced patients and was taken twice a day with ritonavir as the boosting agent. The clinical development program conducted research to establish the efficacy and safety of using darunavir boosted with ritonavir in earlier lines of treatment with decreased dosing so that darunavir 800 mg with 100 mg ritonavir once a day is indicated in treatment naïve patients and treatment-experienced patients who are sensitive to darunavir. Additional work was done to show that cobicistat could replace ritonavir as the booster," Chloe Orkin, chair of the British HIV Association (BHIVA) and consultant physician at the Royal London Hospital told Contagion® via email correspondence.
The investigational single-tablet regimen consists 800 mg of darunavir, 150 mg of cobicistat, 200mg of emtricitabine, and 10 mg of tenofovir alafenamide (D/C/F/TAF).
For the AMBER study, investigators randomly assigned HIV-1 treatment-naïve patients into 2 groups to analyze the safety and efficacy of D/C/F/TAF compared with a control (which consisted of 2 separate medications: D/C plus F/TDF).
"The primary endpoint was to determine noninferiority in efficacy by evaluating the virologic response rate of D/C/F/TAF versus control at week 48 by assessing the proportion of patients that achieved a viral load [VL] of less than 50 copies per mL per FDA Snapshot analysis, at 48 weeks," Professor Orkin told Contagion®. At 48 weeks, the primary endpoint was reached. "At week 48, DCFTAF resulted in high rates of virologic suppression and was non-inferior to D/C plus F/TDF (91.4% D/C/F/TAF vs. 88.4 DC plus F/TDF). There were no darunavir, primary protease or TDF/TAF resistance-associated mutations that developed during the study or discontinuation due to CNS, renal or bone effects," Orkin said.
In addition, the investigational STR proved to have more favorable bone and renal safety parameters compared with the control. "There were few serious adverse events and favorable bone and renal tubular safety outcomes, which were consistent with the safety profile of TAF," Professor Orkin said.
“The 48-week AMBER results demonstrated that if approved in the United States, the investigational darunavir-based STR—combining the durability and high genetic barrier to resistance of darunavir with the safety profile of TAF—could provide a complete and simplified regimen for treatment-naïve patients who may struggle with adherence, and in turn, face the risk of developing drug resistance,” Rick Nettles, MD, vice president of Medical Affairs at Janssen Infectious Diseases shared in the press release.
A new drug application was filed for the STR for treatment of HIV-1 infected adults and pediatric patients 12 years of age and older on September 22, 2017. The European Commission approved the STR to treat adults as well as those aged 12 and older (with a body weight of at least 40 kg) who have HIV-1 infection.
"The 48-week AMBER study results in treatment-naïve patients further build on the growing clinical data set and demonstrate the safety and efficacy of darunavir in a once-daily, single-pill dosing regimen. It follows the recent presentation of pivotal Phase 3 EMERALD study results at IDWeek, which evaluated switching to D/C/F/TAF vs. continuing treatment with a boosted PI plus F/TDF in HIV-1 positive, virologically suppressed adults," Professor Orkin told Contagion®.