Competition for KRAS targeted anticancer drugs

Seven companies are in clinical trials to chase Amgen, the leader

Mechanism of action of KRAS inhibitor (Data: Amgen)

The development of treatments targeting KRAS mutations in solid cancers, including non-small cell lung cancer, is active.

 

This year alone, seven companies were approved for nine related clinical trials.

 

Amgen, which is leading the competition, is undergoing a domestic permit review.

 

According to the pharmaceutical industry on the 30th, there are a total of nine clinical trials related to KRAS that have been approved by the MFDS this year.

 

The nine development stages were 5 cases in phase 1, 2 cases in phase 1/2, and 2 cases in phase 3.

 

KRAS was first discovered in 1982 as a genetic mutation in solid cancers such as non-small cell lung cancer and colon cancer.

 

In lung adenocarcinoma, patients with KRAS mutation are reported to be up to 25% in the West, and about 10-15% in Asians.

 

Development efforts have continued for about 40 years since the discovery of KRAS, but have repeatedly failed in clinical trials.

 

Since then, the KRAS gene signaling system has focused on subdivided targeted treatments tailored to various subtypes such as G12C, G12D, and G12F.

 

Among them, many drugs target G12C.

 

Amgen developed the first targeted treatment targeting KRAS G12C, which was approved by the U.S.

 

Food and Drug Administration (FDA) in May this year under the name Lumakras.

 

Amgen is speeding up its commercialization by applying for permission in Korea immediately.

 

Competition to catch up with Amgen is intensifying.

 

The pharmaceutical company closely chasing Amgen was approved for two phase 3 in June and September by Mirati Therapheutics.

 

One case is for non-small cell lung cancer and the other for colon rectal cancer.

 

Colorectal cancer is used in combination with the existing treatment Erbitux.

 

KRAS development by Mirati and other pharmaceutical companies is still in its infancy.

 

Novartis and China's InventisBio are conducting phase 1/2 each.

 

Novartis tests the KRAS target anticancer drug JDQ443, which is being developed for advanced solid cancer patients in clinical trials approved in March.

 

InventisBio was approved for clinical trials of "D-1553" in March.

 

InventisBio is scheduled to end the test in October 2023 and Novartis in October 2024.

 

Roche, Beringer Ingelheim, and Lilly have also started to develop KRAS-targeted anticancer drugs.

 

Genentech, a Roche subsidiary that was first approved for clinical trials in March this year, plans to evaluate the safety and appropriate capacity of GDC-6036 for solid cancer patients with KRAS G12C mutations by February 2024.

 

In April, Beringer Ingelheim was approved for two first phases of the new drug BI 1701963.

 

One case is a clinical trial in which BI 1701963 monotherapy and another new drug, MEK inhibitor BI3011441 are tested in patients with KRAS mutated solid cancer.

 

The other case evaluates BI 1701963 monotherapy and combination therapy with the existing MEK inhibitor Meqsel in the same patient group.

 

BI 1701963, which is being developed by Beringer Ingelheim, is a general-purpose treatment (pan-KRAS) that targets various types of KRAS mutations, including major G12 genes.

 

Its strategy is to maximize its effectiveness by using it in combination with MEK inhibitors.

 

Most recently, Eli Lilly also jumped into domestic development with the approval of the first award.

 

Lilly stopped KRAS-targeted new drug substance, which was being developed first last year, due to toxicity problems.

 

Lilly did not stop here, but began to try again with another new drug called "LY3537982." Lilly is planning to conduct phase 1 for solid cancer patients with mutations in KRAS G12C.

 

MSD continues to develop an immuno-cancer drug Keytruda in combination with KRAS-targeted anticancer drugs.