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Article source: Medical Rubik's Cube Pro
Author: Leaf
Breast cancer is one of the leading causes of cancer deaths in women worldwide
ARV-471 is a selective, orally bioavailable proteolytic targeting chimera (PROTAC) small molecule that can induce the degradation of wild-type and mutant ER
On December 10, at the 44th San Antonio Breast Cancer Symposium (2021 SABCS), ARV-471 updated the safety and activity data for the first time in patients with ER+/HER2- locally advanced or metastatic breast cancer
The study used a conventional 3+3 dose escalation study to evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary effects of oral ARV-471 in pre/postmenopausal women with ER+/HER2-locally advanced or metastatic breast cancer Anti-tumor activity
2021SABCS
As of September 30, 2021, 60 patients have been treated in the phase 1 dose escalation cohort, and the total daily dose of ARV-471 ranges from 30 mg to 700 mg
The most common (≥10%) treatment-related adverse events (TRAE) were mainly grade 1 nausea (27%), fatigue (20%) and vomiting (10%)
Preliminary pharmacokinetic data showed that the AUC24 and Cmax of ARV-471 ranged from 30 mg to 500 mg, showing a dose-related increase in plasma exposure
PROTAC drugs were once seen by the industry as their solution to the drug resistance problem.
Clinical evaluation data disclosed for the first time (Source: Arvinas)
2021 SABCS
Of course, there are many reasons for this phenomenon.
Degradation ratio of ER under different doses (Source: Arvinas)
In fact, in theory, the PROTAC drug molecule is a catalytic function, and if it is efficient enough, it can completely degrade the target protein
ARV-471 blood concentration-time relationship graph (Source: Arvinas)
In addition, experts pointed out that most patients with CDK4/6 inhibitor progression are ER-independent drug resistance.
As far as the current data is concerned, the biggest advantage of ARV-471 is still safety.
ARV-471 Development Plan (Source: Arvinas)
In July, Pfizer obtained ARV-471 global rights with an advance payment of US$650 million and a milestone payment of US$1.
