ESSA Pharma and Astellas Launch Phase II Clinical Trial of First-in-Class Androgen Receptor N-Terminal Domain Inhibitor EPI-7386 in Combination with Enzalutamide for mCRPC
Jan 22, 2022 01:35
CST Updated
01:35
ESSA Pharma
Small Molecule Drug Developer
Astellas
Pharmaceutical R&D Manufacturer
Prostate Cancer (Image Source: hopkinsmedicine.org)
News on January 21, 2022 /BioValleyBIOON/ -- ESSA Pharma, a clinical-stage pharmaceutical company focused on developing innovative therapies for prostate cancer, recently announced that the first patient has been dosed in its sponsored Phase 1/2 clinical study (NCT05075577) conducted in collaboration with Astellas. The study is evaluating the safety, tolerability, and preliminary efficacy of its lead candidate drug EPI-7386 in combination with Xtandi® (generic name: enzalutamide) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
EPI-7386 is a first-in-class, orally administered, highly selective, small-molecule inhibitor of the N-terminal domain (NTD) of the androgen receptor.This drug belongs to a new class of compounds called "enitens," which are designed toInhibition of Androgen Receptor Activity by Targeting the Androgen Receptor NTD. Previously, the United StatesFDAEPI-7386 has been granted Fast Track Designation (FTD) for the treatment of adult male patients with mCRPC who are resistant to standard-of-care therapies. Currently, ESSA Pharma, Inc. has partnered with Astellas, Johnson & Johnson,BayerA collaboration was reached to evaluate the combination potential of EPI-7386 with androgen receptor therapies, including Xtandi (enzalutamide,Pfizer/Astellas), Zytiga (abiraterone acetate, Johnson & Johnson), Erleada (apalutamide, Johnson & Johnson), Nubeqa (darolutamide, Bayer).
Xtandi is an androgen receptor ligand-binding domain (LBD) inhibitor developed through a collaboration between Astellas and Pfizer.To date, Xtandi has been approved for the treatment of three different types of advanced prostate cancer, including: non-metastatic and metastatic castration-resistant prostate cancer (CRPC), and metastatic hormone-sensitive prostate cancer (mHSPC). In China, Xtandi (Ankotan®, enzalutamide) was approved in November 2019 and November 2020, respectively, for: (1) the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or have mild symptoms and have not received chemotherapy after failure of androgen deprivation therapy (ADT); (2) the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) at high risk of metastasis.
The combination of the two therapies will simultaneously target both ends of the androgen receptor.Among them, EPI-7386 acts on the N-terminal domain of the androgen receptor, while Xtandi acts on the ligand-binding domain of the androgen receptor.。Inhibiting the androgen receptor through two independent pathways has the potential to bring greater clinical benefits to patients with mCRPC.. This has been observed in preclinical models,The combination regimen of EPI-7386 with existing anti-androgen drugs,Can lead to a deeper and broader suppression of androgen biology。
Mechanism of Action of EPI-7386 in Combination with Current Anti-Androgen Receptor Therapies (Click Image to Enlarge)
This Phase 1/2 clinical study will begin with the Phase 1 portion, adjusting the dosage of each drug; followed by the Phase 2 portion, which will compare Xtandi monotherapy with the Xtandi+EPI-7386 combination therapy. The Phase 1 study is expected to enroll 30 mCRPC patients who have not yet received second-generation anti-androgen therapy, with the aim of evaluating the safety and tolerability of the combination therapy and determining the recommended Phase 2 doses of EPI-7386 and Xtandi when used in combination.
Phase 2 Study Expected to Enroll 120 mCRPC Patients Who Have Not Yet Received Second-Generation Anti-Androgen Therapy, Aiming to Evaluate the Safety, Tolerability, and Antitumor Activity of EPI-7386 in Combination with a Fixed Dose of Xtandi Compared to Xtandi MonotherapyTumorActivity.
ESSA Pharma CEO Dr. David R. Parkinson stated, "The launch of this collaboration trial with Astellas marks a watershed moment for ESSA as we explore the potential clinical benefits of inhibiting the androgen receptor through two independent pathways for treating mCRPC patients who have not yet received second-generation anti-androgen therapy. The two therapies will simultaneously target both ends of the androgen receptor. In preclinical models, we have observed that combining EPI-7386 with existing anti-androgen drugs leads to deeper and broader suppression of androgen biology. This Phase 1/2 trial represents the first in a series of clinical studies that will evaluate the combination of EPI-7386 with other anti-androgen drugs." Current anti-androgen treatments for mCRPC patients are expected to be followed by additional Phase 1/2 combination trials starting in 2022. (Bioon.com)