The introduction of KRAS inhibitors has become a significant advancement in the quickly developing area of oncology, providing hope in the battle against difficult solid tumors.
In fact, the global market for KRAS-targeting drugs in oncology is set to reach over $4 billion by 2029, forecasts data and analytics company GlobalData.
GlobalData reveals that Mirati Therapeutics is expected to emerge as the leader in this rapidly expanding market, as its small-molecule KRAS G12C inhibitor Krazati is anticipated to secure a 30.7% market share with a worldwide sales of $1.2 billion by 2029.
Following closely behind Mirati, Amgen's Lumakras is predicted to attain the second spot with $1 billion sales, representing 25.4% of the overall KRAS-targeting therapy market share by 2029.
Biswajit Podder, oncology and hematology analyst at GlobalData, comments: “The emergence of KRAS-targeting therapy marks a turning point in non-small cell lung cancer (NSCLC) treatment.
“According to GlobalData’s patient-based forecast, the total sales of Krazati and Lumakras will reach $1.4 billion for NSCLC treatment by 2029 in the eight major markets (US, France, Germany, Italy, Spain, UK, Japan, and China). In addition, these two drugs are in multiple clinical trials for several solid cancers, including colorectal cancer, pancreatic cancer, breast cancer, ovarian cancer, and bile duct cancer.”
To date, the FDA has only approved two commercial KRAS inhibitor drugs for cancer treatment.
However, the sector has seen substantial expansion since 2019, with 110 distinct phase 1 to 3 trials employing different KRAS-targeting therapies. In 2020 and 2021, there were 14 and 33 ongoing trials, respectively, showing a clear growth trend.
This upward trajectory continued into 2022 and 2023, with each year witnessing 51 ongoing trials, demonstrating an ‘active pipeline’ and ‘steadfast commitment’ to developing KRAS-targeting treatments, GlobalData says.
Along with KRAS inhibitors like Roche’s divarasib and Novartis’s opnurasib, Revolution Medicines is also in the race to bring about significant changes with three different KRAS inhibitors in the pipeline.
One of Revolution Medicines' G12C mutant-selective KRAS inhibitors is RMC-6291. It has a different mechanism of action than the approved KRAS inhibitors Krazati and Lumakras, targeting the inactive KRAS state. RMC-6291 acts as a 'molecular glue'.
It binds to cyclophilin A, a ubiquitous protein that forms a complex with KRAS G12C in its active state.
Podder concludes: “In addition, the phase 1 trial results of RMC-6291 presented at the Triple (EORTC-NCI-AACR) meeting in October, demonstrated good early tolerability, safety, and distinct anti-tumor efficacy. This approach might provide precise tumor targeting, less off-target effects, and deeper suppression, with the added benefit of overcoming some of the acquired resistance mechanisms seen with approved inhibitors.”
