KRAS is one of the first oncogenes to be discovered, and its mutation is present in about 1/4 of human tumors, and is one of the clear targets in the field of
oncology drug discovery.
However, because the protein is a featureless, almost spherical structure with no obvious binding site, it is difficult to synthesize a compound that can target binding and inhibit phase activity, and KRAS has been almost impossible to conquer
for a long time.
Although global pharmaceutical companies have repeatedly failed, they are still persevering in the development of KRAS G12C inhibitors
.
It is reported that there is currently a KRAS target drug worldwide, Amgen's Sotorasib, which was approved by the FDA in May 2021 for the treatment of patients with locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations who have received at least one previous systematic therapy
.
And as global pharmaceutical companies continue to lose repeated battles, a number of KRAS G12C inhibitors are currently in the late clinical stage
.
The industry said that in the next few years, KRAS G12C inhibitors are expected to usher in a commercial harvest period, which also means that a new round of tumor new drug research competition has begun
fiercely.
Data show that there are currently 49 KRAS G12C inhibitors under research worldwide, and more than 20 are in the clinical stage
.
In addition to the marketed Sotorasib, Mirati Therapeutics' Adagrasib (MRTX849) has submitted a new drug application to the US FDA; JDQ443 developed by Novartis is in phase III clinical trials for non-small cell lung cancer
.
In China, there are a total of 15 products under development, of which 14 have entered the clinical stage
.
From the perspective of the domestic market, the current rapid progress includes Zai Lab's Adagrasib, Yifang's D-1553, Innovent/GenFleet's GFH925, Suzhou Zejing Biologics' ZG19018, Jiyu Pharmaceutical's JMKX001899, Jacobio's JAB-21822 and Novartis' JDQ443
.
Zai Lab completed the first patient dosing of the Adagrasib Global Phase III clinical study KRYSTAL-10 in Greater China in June 2022 to evaluate the use of adagrasib in combination with cetuximab in patients with advanced colorectal cancer with KRASG12C mutation; In July 2022, the first patient dosing of KRYSTAL-12 in Greater China was completed in the global phase III clinical study, which aims to evaluate adagrasib for the treatment
of patients with advanced NSCLC with KRASG12C mutation.
Yifang's D-1553 is currently undergoing Phase II clinical trials
.
It is reported that in June 2022, CDE announced that it intends to include Yifang Biotechnology's D-1553 tablets into breakthrough therapy for patients
with locally advanced or metastatic non-small cell lung cancer who have disease progression after previous anti-PD-(L)1 therapy and/or chemotherapy, and have been confirmed by testing to have KRAS G12C mutations and no other driver gene mutations or rearrangements (such as EGFR, ALK and ROS1).
Innovent/GenFleet's GFH925 submitted its first clinical application to NMPA in May 2021; A Phase I/II clinical trial was initiated in August of the same year; In September, Innovent partnered with GenFleet, under which Innovent will acquire the development and commercialization rights of Genfleet's GFH925 in Greater China as an exclusive partner, with the option to develop and commercialize globally
.
Suzhou Zejing Biotech's ZG19018, Jiyu Pharmaceutical's JMKX001899, Jacobio's JAB-21822 and Novartis' JDQ443 are also in phase I/II clinical trials
.
In addition, BeiGene reached a strategic cooperation
with Amgen in October 2019 on the development and Chinese mainland commercialization of products such as LUMAKRASTM (Sotorasib).
In January 2021, Sotorasib received breakthrough therapy designation
from the NMPA.
According to Frost & Sullivan, the number of major KRAS G12C mutation-positive cancers worldwide increased from 270,000 to 300,000 between 2016 and 2020 and is expected to grow to 341,000 by 2025
.
It can be seen that the market for KRAS G12C inhibitors is broad.
The industry said that based on this, global pharmaceutical companies have entered the development of KRAS G12C inhibitors
.
={"common":{"bdSnsKey":{},"bdText":"","bdMini":"1","bdMiniList":false,"bdPic":"","bdStyle":"0","bdSize":"32"},"share":{},"image":{"viewList":[" weixin","sqq","qzone","tsina","tqq","tsohu","tieba","renren","youdao","fx","ty","fbook","twi","copy","print"],"viewText":"share:","viewSize":"24"},"selectShare":{" bdContainerClass":null,"bdSelectMiniList":["weixin","sqq","qzone","tsina","tqq","tsohu","tieba","renren","youdao","fx","ty","fbook","twi","copy","print"]}}; with(document)0[(getElementsByTagName('head')[0]|| body).
appendChild(createElement('script')).
src='http://bdimg.
share.
baidu.
com/static/api/js/share.
js?v=89860593.
js?cdnversion='+~(-new Date()/36e5)]; 
