Erleada Keeps Pace With Xtandi After Positive TITAN Study
Executive Summary
Metastatic castration-sensitive prostate cancer could see a marketing race following positive top-line clinical data for Janssen’s apalutamide in the Phase III TITAN study.
Johnson & Johnson’s prostate cancer therapy Erleada (apalutamide) is quickly advancing its clinical trial program into potential new indications, virtually matching the progress of key competitor Xtandi (enzalutamide) and differentiating it from generics of its first-generation agent, Zytiga (abiraterone acetate).
Erleada met both primary endpoints in the ongoing TITAN Phase III study in patients with metastatic castration-sensitive prostate cancer, leading J&J to unblind the trial so that placebo-treated patients can cross over to the active group, the big pharma announced on Jan. 30.
The unblinding follows a positive pre-planned analysis by the study’s Independent Data Monitoring Committee, and J&J’s Janssen Pharmaceutical Cos. said it would be submitting the additional indication evaluated in TITAN to regulatory authorities in 2019.
Janssen gave few details about the strength of Erleada’s efficacy in the TITAN study in newly diagnosed metastatic castration-sensitive prostate cancer, beyond saying patients treated with apalutamide plus androgen deprivation therapy (ADT) showed a significant improvement in radiographic progression-free survival (rPFS) and overall survival, the dual primary endpoints. Further results will be submitted for presentation at an upcoming medical conference.
Still, the unblinding of the TITAN trial suggested that “Erleada provided a very clear benefit in terms of efficacy,” opined analysts at Informa’s drug pipeline database, Biomedtracker. Further, with the TITAN trial “meeting both primary endpoints well ahead of its primary completion date of November 2020, J&J will be able to keep pace with Pfizer Inc. and Astellas Pharma Inc., the marketers of the competing androgen receptor antagonist, Xtandi,” the Biomedtracker analysts add.
That is because on Dec. 20, 2018, Pfizer and Astellas announced positive top-line data from the Phase III ARCHES trial in men with metastatic hormone-sensitive prostate cancer, showing that Xtandi met its primary endpoint of rPFS. That is more than a year ahead of its initial primary completion date of April 2020, Biomedtracker analysts noted.
Xtandi is currently approved in the US and Japan for the treatment of castration-resistant prostate cancer (CRPC), and in the EU for metastatic and high-risk non-metastatic CRPC. It is also being evaluated in the EMBARK study in patient with high-risk non-metastatic hormone-sensitive prostate cancer.
Informa’s Datamonitor Healthcare estimates the prostate cancer market could grow by more than 30% to be worth $11.2bn in 2026 in the US and top-five EU markets, driven by the launch of new therapies across different treatment settings and the increasing prevalence of the condition, offsetting erosion from the launch of generic versions of Zytiga.
J&J indicated during its recent fourth quarter earnings call that generic competition in the US to Zytiga had been seen in the final quarter of 2018, and Zytiga US sales in the quarter were down 12.7%. (Also see "Two Years On The Market And Only A 7% Volume Share – J&J Numbers Reveal Infliximab Struggle For US Biosimilars" - Generics Bulletin, 23 Jan, 2019.)
The pharma industry’s R&D pipeline is also packed with potential therapies for prostate cancer, and those in late development include Bayer AG’s darolutamide, the PARP inhibitors, Clovis Oncology Inc.’s Rubraca (rucaparib) and AstraZeneca PLC/Merck & Co. Inc..’s Lynparza (olaparib) and various immuno-oncology agents, including Roche’s Tecentriq (atezolizumab). (Also see "Clovis In Pole Position To Be First PARP For Prostate Cancer" - Scrip, 22 Oct, 2018.)
Erleada, a next-generation androgen receptor inhibitor, was first launched in the US in early 2018 for non-metastatic castration-resistant prostate cancer, and a similar approval has just been achieved in Europe (see sidebar).
Erleada’s Long-Term Safety
The TITAN monitoring committee recommended that patients in the placebo plus ADT group should be given the opportunity to be treated with apalutamide plus ADT, as well as all patients being followed for overall survival and long-term safety. Just over 1,000 patients were randomized into the study, and patients treated until disease progression or unacceptable treatment-related toxicity. Secondary endpoints include time to chemotherapy, time to pain progression, time to chronic opioid use and time to skeletal-related event.