- In patients with metastatic prostate cancer, ARV-766 treatment led to a greater than 50% reduction in Prostate-Specific antigen (PSA) in 42% of patients with resistance mutations in their androgen receptor.
- ARV-766 is an oral medication that was well-tolerated with no grade 4 treatment-related adverse events or dose-limiting toxicities.
The Latest
In 2021, ARVINAS started a phase-1/2 trial of 47 men with metastatic prostate cancer who have previously received at least one line of treatment with androgen receptor (AR) inhibitors. Preliminary data from the study showed that ARV-766 led to a greater than 50% reduction in Prostate-Specific antigen (PSA) in 42% of patients with AR resistance mutations. ARV-766 was well tolerated with no grade 4 treatment-related adverse events or dose-limiting toxicities.
Physician’s Perspective
Prostate cancer is the most prevalent urogenital malignancy in men. Currently, therapies for prostate cancer include androgen deprivation therapy which can be achieved either surgically or medically through suppression of androgen signaling. Unfortunately, many patients eventually progress in their disease while receiving androgen deprivation therapy, resulting in a disease state known as castration-resistant prostate cancer (CRPC). One of the mechanisms of disease progression is thought to be the development of resistance to androgen receptor inhibition. For patients who have developed resistance to androgen receptor inhibitors, ARV-766 may still offer therapeutic benefits by binding to mutated androgen receptors and targeting them for degradation, thereby enabling continued androgen signaling inhibition.
Molecular Target of Therapy
The degradation technique ARVINAS utilizes harnesses the body’s intrinsic system of using an E3 ligase to target misfolded proteins for degradation. ARV-766 is a novel protein that contains regions that simultaneously bind the wild-type or mutant androgen receptor (AR) as well as the E3 ligase, which targets the androgen receptor for degradation.
Company History
ARVINAS is a New Haven, Connecticut-based clinical-state biotechnology company that was started in 2013 by Craig Crews. Based on the promising data from the phase-1/2 trial of ARV-766, ARVINAS entered into an exclusive strategic license agreement with NORVATIS for further development and commercialization of ARV-766. ARVINAS will receive an upfront payment of $150 million for the ARV-766 license as well as additional development, regulatory, and commercial milestones of up to $1.01 billion. In addition to metastatic prostate cancer, ARVINAS is also designing novel proteins targeting metastatic breast cancer and neurological disease.
Further reading: https://ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.TPS290
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