The latest data of Arvinas androgen receptor PROTAC therapy show sustained anti-tumor activity

February 21, 2022/eMedClub PR News/--On February 17, 2022, Arvinas, a clinical-stage biotechnology company, announced the completion of bavdegalutamide, a novel PROTAC® protein degrader targeting the androgen receptor (AR).
Latest results from Phase 1 and Phase 2 clinical trials of (ARV-110)
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These clinical trial data demonstrate potent antitumor activity and clinical benefit in the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients with AR T878X and/or H875Y (T878X = T878A or T878S) mutations
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These results also showed that in patients with tumors without the AR T878X/H875Y mutation, the use of ARV-110 also showed a decrease in PSA and tumor shrinkage
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"These results reinforce our belief that ARV-110 has the potential to provide meaningful clinical benefit to the patient population following mCPRC progression," said Dr.
John Houston, President and CEO of Arvinas
.
"
These data lead us to believe that there is a clear line The path forward can accelerate this new therapy or will become the patient’s choice for precision medicine
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” Sustained antitumor activity Bavdegalutamide is a “first in class” PROTAC protein degrader developed by Arvinas that selectively targets AR proteins
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Its clinical data are as of December 20, 2021.
Among the 140 biomarker-evaluable patients with PSA follow-up ≥1 month in the Phase 1 clinical trial and the mid-phase ARDENT expansion cohort of the Phase 2 clinical trial, the relevant clinical data indicate: 46% of patients with AR T878X/H875Y-mutated tumors had a ≥50% reduction in PSA level (PSA50); of 7 RECIST-evaluable patients with AR T878X/H875Y tumor mutations, 2 had confirmed partial responses and 6 had tumor shrinkage ; PSA50 rate was 22% (6 of 27) in evaluable patients in the preconditioning subgroup (who had received only one prior novel hormonal drug and no prior chemotherapy)
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The majority of patients in this group with decreased PSA50 had tumors with AR T878X/H875Y mutations
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Bavdegalutamide was well tolerated at the recommended phase 2 dose (RP2D) of 420 mg
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Among the 113 patients treated with RP2D, the majority of treatment-related adverse events (TRAEs) were grade 1/2, and there were no grade ≥ 4 TRAEs
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▲ Image source: Arvinas official website Arvinas plans to initiate a pivotal trial at the end of the year to evaluate the efficacy of bavdegalutamide in patients with mCRPC with AR T878X/H875Y mutations during or after receiving a new hormonal drug (NHA)
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In addition, Arvinas plans to start discussions with the U.
S.
FDA to explore a pathway that could expedite approval of the drug
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The concept of PROTAC PROTAC targeting AR and ER was first proposed by Crews et al.
in 2001.
It can utilize the naturally occurring protein clearance system in the body to reduce protein levels in an "event"-driven manner, but not inhibit protein function, thereby exerting The role of the treatment of disease
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Arvinas is one of the pioneers in the exploration of PROTAC protein degrader technology.
The ARV-110 and ARV-471 developed by Arvinas have shown great potential in clinical data for the treatment of prostate cancer and breast cancer, opening the door for global targeting of "difficult-to-drug" targets.
A new door
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▲ R&D pipeline (Image source: Arvinas official website) As mentioned earlier, ARV-110 is a PROTAC protein degrader targeting androgen receptor (AR), so AR activity is a key driver of prostate cancer, the ability to regulate AR signaling is an important factor in the control of disease progression
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ARV-766 is also an androgen receptor (AR) targeted, but has different characteristics from ARV-110, which is currently in Phase 1 clinical trials
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ARV-471 is an oral estrogen receptor (ER)-targeted PROTAC protein degrader for the treatment of patients with localized or metastatic ER-positive/HER2-negative breast cancer
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On July 22, 2021, Arvinas and Pfizer entered into a collaboration agreement to jointly develop and commercialize the ER degrader ARV-471, which is currently in Phase 2 clinical trials
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In future studies, Arvinas intends to use ARV-471 as a single agent in combination with other therapies such as CDK4/6 inhibitors
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In addition, in addition to being favored by Pfizer, Arvinas has also established partnerships with pharmaceutical giants such as Merck, Genentech, and Bayer
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Recommended reading: Over $2 Billion! Pfizer and Arvinas collaborate to create protein degradation therapy for breast cancerYimai Meng revealed that there is also an exploratory androgen receptor (AR) splice variant AR-V7, which targets PROTAC protein degradation agent is the next generation AR PROTAC , which can target both AR-V7 and full-length AR
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Summary According to incomplete statistics, more than 100 proteins have been successfully degraded by PROTAC, and substantial breakthroughs have been made in the research on many "difficult-to-be-drug" targets and drug resistance problems.
The disclosed targets mainly include the following categories: Including kinases, BET proteins, nuclear receptors and other proteins
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At present, PROTAC technology and R&D have mature experience in foreign countries.
Leading technology companies include Arvinas, Kymera, Nurix and C4 Therapeutics
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Novartis, Pfizer, Merck, Bayer, Genentech, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Celgene, Amgen, Eli Lilly, Gilead, AbbVie, Johnson & Johnson and other leading companies are focusing on the field
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For this technology, although China is in the "pioneering" stage, more and more companies are entering this track to compete, but they are currently in the early research stage
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It is believed that with the continuous research of the technology in the later stage, the technology will be gradually expanded in the market
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References: 1.
https:// https://ir.
arvinas.
com/news-releases/news-release-details/arvinas-protacr-protein-degrader-bavdegalutamide -arv-110 statement: The content of this article is only for exploring the frontier progress of biomedicine and does not constitute any medical guidance.
If you need it, please go to a regular hospital for treatment
.