Studies have shown that mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) are one of the most frequently occurring genomic alterations in solid tumors including lung cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. The KRAS mutation confers permanent activation of the KRAS protein, which acts as a molecular switch to activate various signaling pathways and transcription factors which induces cell proliferation, migration, transformation, and cell survival. Therefore, KRAS emerged out to be of great interest for researchers and considerable efforts have been done to develop drugs targeting KRAS mutation.
Recently, Amgen has developed Lumakras which is the first (Solatraib) which is the first targeted drug which is approved for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer. The drug normally binds to cysteine residue in KRAS G12C mutations, holding the protein in its inactive form, thus inhibiting the MAP kinase pathway. The clinical trials with the drug demonstrated high efficacy and considerable increase in overall survival and progression free survival rates of NSCLC patients. The introduction of Lumakras in the market is expected to witness high adoption rates owing to its specific mechanism of action and unavailability of other KRAS targeting drugs in the market.
The robust response of Lumakras in the market has further surge the research and development in this sector. For instance in July, 2021 US FDA has granted breakthrough therapy designation to adagrasib for the treatment of patients with previously treated KRAS G12C–mutant NSCLC. Adagrasib is investigational, highly selective, oral small molecule inhibitor of KRAS which has shown enhanced efficacy to Lumakras. It is expected that the drug will enter US market by 2022 and will compete with Lumakras in forth coming years. Apart from NSCLC, the investigational drug is also being evaluated in other cancers also including colorectal cancer, pancreatic cancer, and other solid tumors harboring KRAS G12C mutations.
Despite their promising results, emerging evidences from preclinical and clinical trial shows that drug resistance is one of major restrain in the market. However, several clinical trials are ongoing to overcome the limitations by combining the drug with other modalities to enhance its therapeutic effect. For instance, Verastem Oncology in collaboration with Amgen is evaluating VS-6766 in combination with Lumakras in patients with NSCLC. Apart from this, several next generation KRAS inhibitors have also been developed which are expected to gain approval during the forecast period.
The global KRAS inhibitor market was valued to be around US$ XX Million in 2020 and is expected to grow with high CAGR rates during forecast period. The transient shift towards sedentary lifestyle and the increase in uptake of smoking, alcohol and tobacco consumption will led to rise in prevalence of lung cancer which will further propel the market. Moreover, the rates at which conventional therapies are failing possess an unmet need for the novel targeted therapy in the management of cancer. The market for KRAS inhibitor is highly competitive and consists of several key players such as Eli Lilly, Merck, Mirati Therapeutics, Gilead, Revolution Medicines, and others.
US is expected to dominate the market throughout the forecast period. The dominance is due to growing prevalence of cancer, presence of majority of pharmaceutical giants, huge investment in research and development in the region. Furthermore, US government has also developed favorable reimbursement policies like Amgen Assist 360 to reduce financial toxicity and enhance adoption rates in the population, which will further propel regional market. Apart from US, market in Europe, China and Japan is expected to flourish in coming years with the approval of Lumakras in coming months.