On May 29, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biopharmaceutical company creating a new class of therapies that degrades disease-causing proteins, reported that its lead PROTAC protein degrader, ARV-110, has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed after treatment with two or more systemic therapies (Press release, Arvinas, MAY 29, 2019, View Source [SID1234536646]). ARV-110 is an orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR) protein. ARV-110 is currently being evaluated in a Phase 1 clinical trial designed to evaluate the safety, tolerability, and pharmacokinetics of ARV-110 in men with mCRPC whose disease has progressed after treatment with standard of care therapies.
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"While great strides have been made in the treatment of men with metastatic castration-resistant prostate cancer, current AR-targeted standard of care treatments are less effective in patients whose disease includes increased levels of androgen production or mutations in the androgen receptor," said John Houston, Ph.D., President and Chief Executive Officer of Arvinas. "We believe, due to its ability to iteratively degrade the AR protein, ARV-110 could represent a meaningful new therapy to improve the lives of patients battling mCRPC, and for whom current therapies are not effective. The Fast Track designation by the FDA recognizes the urgency for improved treatments for these patients."
About Metastatic Castration-Resistant Prostate Cancer (mCRPC)
In the United States, prostate cancer is both the second most prevalent cancer in men and the second leading cause of cancer death in men. The American Cancer Society predicts that one in nine men will be diagnosed with prostate cancer in his lifetime. Metastatic castration-resistant prostate cancer (mCRPC) is defined by disease progression despite androgen deprivation therapy and is often correlated with rising levels of prostate-specific antigen (PSA).
Current AR-targeted standard of care treatments for mCRPC are less effective in patients whose disease has increased levels of androgen production, AR gene or gene enhancer amplification, or AR point mutations. Between 15-25% of patients do not respond to second-generation hormone therapies like abiraterone and enzalutamide, and the majority of responsive patients will ultimately become resistant, resulting in poor prognoses for men diagnosed with this devastating condition.
About PROTAC Protein Degraders
Arvinas’ PROTAC protein degraders harness the body’s own natural protein disposal system to degrade disease-causing proteins. PROTAC protein degraders recruit an E3 ligase to tag the target protein with ubiquitin, which directs its degradation through the proteasome, a large protein complex that breaks down the ubiquitinated target protein into small peptides and amino acids. As the target protein is degraded, the PROTAC protein degrader is released and acts iteratively to destroy additional target protein.
PROTAC protein degraders offer numerous potential therapeutic advantages, including broad tissue distribution, routes of administration that include oral delivery, and simpler manufacturing than other new modalities, such as cell-based therapies. Arvinas has developed and optimized a proprietary library of protein targeting ligands, E3 ligase ligands, and linkers, which allow the company to rapidly identify and optimize efficient protein degraders with favorable characteristics for successful drug development.
About ARV-110
ARV-110 is an orally bioavailable PROTAC protein degrader designed to selectively target and degrade androgen receptor (AR) protein. ARV-110 is being developed as a potential treatment for men with mCRPC. ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies. Arvinas believes the differentiated pharmacology of ARV-110, including its iterative activity, has the potential to translate into improved clinical outcomes for patients.
The Phase 1 clinical trial of ARV-110, for men with mCRPC whose disease has progressed after treatment with standard of care therapies, began in 1Q2019. Preliminary clinical data for the trial will be shared in 2H2019, including safety, tolerability, and PK data. Full disclosure of trial information is expected in 1H2020, including prostate-specific antigen (PSA) data and Response Evaluation Criteria in Solid Tumors (RECIST) data.