Early but strong clinical data of Arvinas’s ARV-110 in Men with mCRPC that support a potential path to accelerated approval

Major Key player Arvinas announced completed Phase I and interim Phase II ARDENT data for ARV-110 degrader targeting the androgen receptor (AR). According to the results, Arvinas mentioned that at the data cut-off date, December 20, 2021, the PSA₅₀ response rate was 46% in 28 patients with AR T878X/H875Y tumor mutations and the PSA decline of more than 30% (PSA30) response rate was 57%. In addition to that, ARV-110 had a manageable tolerability profile at the recommended Phase II dose (RP2D) of 420 mg oral, once daily. These data continue to provide evidence of anti-tumor activity and clinical benefit in patients with mCRPC. Arvinas plans to begin discussions with the US Food and Drug Administration (FDA) in the first half of 2022 about the possibility of an accelerated approval pathway for bavdegalutamide in a molecularly characterized mCRPC group. In addition to this, the company also intends to start a pivotal study (patients with AR T878/H875 tumor mutations) before the end of the year.

Analyst Opinion: Targeted protein degradation has evolved from academia to industry in recent years, and the foundational era of Targeted protein degradation was capped in 2019 with the first PROTAC degrader, bavdegalutamide (ARV-110), entering the clinical trials. Given the current state of events, bavdegalutamide has the potential to provide therapeutic benefits to a patient group with limited options following the progression of their mCRPC. The company is contemplating an accelerated route to market for post-next generation hormonal agents (NHAs) patients via a companion diagnostic approach. Not only that, but the company will explore the possibilities in an earlier-stage, bigger patient group in the future: Monotherapy or combination treatment (e.g., abiraterone), Pre- and post-NHA, and potential in both CRPC and CSPC. If all goes as planned between Arvinas and the FDA, it will be a watershed event in the history of targeted protein degradation as an emerging cancer therapy modality, especially given that the current era of targeted protein degradation is in its early transitional phases.