How Upcoming KRAS InhibitorsKRAS Inhibitors are Expected to Shape the Future Oncology Market Landscape?
2024-02-26
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KRAS stands out as the most commonly altered among the trio of RAS genes, with NRAS and HRAS following suit. The human KRAS gene resides on chromosome 12p12.1 and comprises six exons, primarily positioned in exon 1 at sites 12 and 13, though occasionally found in codons 61, 63, 117, 119, and 146.
The emergence of KRAS inhibitorsKRAS inhibitors marks a notable advancement in the rapidly progressing field of oncology, instilling hope in combating formidable solid tumors. The landscape of treatment for KRAS-mutant cancers is undergoing rapid evolution, marked by several promising advancements in recent years. Forecasts anticipate significant growth in the KRAS inhibitorsKRAS inhibitors market in the coming years, propelled by rising cancer incidence rates and the escalating demand for personalized cancer therapies. Ongoing research and clinical trials continue to unveil potential treatment strategies, fostering optimism for improved patient outcomes.
According to DelveInsight’s analysis, the market size for KRAS inhibitorsKRAS inhibitors across the 7MM and is expected to grow with a tremendous 36% CAGR to reach USD 10 billion by 2032. As per the estimates, the US is set to be the largest market for KRAS inhibitorsKRAS inhibitors, with ~70% of the market share among the seven major markets. The KRAS inhibitorKRAS inhibitor market is expected to grow significantly in the coming years, driven by the increasing incidence of cancer and the growing demand for personalized cancer treatments; ongoing research and clinical trials have identified potential treatment strategies.
Key players, including Mirati, Novartis Pharmaceuticals, Amgen, Eli Lilly, Verastem, and others, are involved in developing drugs for KRAS mutation for various indications such as NSCLC, colorectal cancer, pancreatic cancer, and others. The treatment landscape for KRAS-mutant cancers has rapidly evolved, with several promising advancements in recent years. Keen to know how the KRAS inhibitorsKRAS inhibitors market will evolve by 2032? Find out @ KRAS InhibitorsKRAS Inhibitors Market Forecast
Amgen and Mirati Therapeutics are at the forefront of the race to develop KRAS inhibitorsKRAS inhibitors for cancer treatment. However, their current candidates are focused solely on targeting G12C-mutant tumors, leaving a significant gap in addressing other KRAS variants. This represents a major unmet need in the field, as no approved treatments are currently available for other variants. Recognizing this challenge, numerous key players actively explore alternative KRAS variants and expand their research to include other types of cancers beyond NSCLC. This shift in focus holds promising potential for developing effective therapies that can address a wider range of KRAS mutations and target multiple cancer types. Many companies are focusing on developing their candidates in pan-KRAS, like Cardiff Oncology (onvansertib), Gritstone bio (SLATE KRAS), Hookipa Pharma (HB-700), and others.
Now, let’s examine the emerging KRAS inhibitorKRAS inhibitor therapies
JDQ443: Novartis Pharmaceuticals
Phase III
JDQ443 represents an experimental KRASG12C inhibitor that is selective, covalent, and can be taken orally. Initial findings from the Phase Ib stage of the KontRASt-01 trial (NCT04699188) indicate a confirmed overall response rate (ORR) of 57% at the recommended dosage of 200 mg twice daily in
individuals with advanced non-small cell lung cancer (NSCLC). Presently, JDQ443 is undergoing Phase III evaluation, aiming to compare its effectiveness as a standalone treatment against docetaxel in patients with advanced NSCLC carrying a KRASG12C mutation who have previously undergone platinum-based chemotherapy and immune checkpoint inhibitor therapy, either sequentially or in combination. Novartis intends to New Drug Application (NDA) for NSCLC by 2024 and for colorectal cancer (CRC) post-2026.
Avutometinib (VS-6766): Verastem Oncology
Phase II
Avutometinib (VS-6766) functions as an RAF/MEK clamp, prompting the formation of inactive complexes involving MEK and ARAF, BRAF, and CRAF. This mechanism potentially enhances the anti-tumor response by thoroughly inhibiting the RAS pathway, possibly leading to more sustained effects. Currently, avutometinib is in advanced stages of development. Unlike other MEK inhibitors, it not only blocks MEK kinase activity but also prevents RAF from phosphorylating MEK. This distinctive mode of action enables avutometinib to inhibit MEK signaling effectively without triggering compensatory activation, a limitation observed in other inhibitors.
The FDA has recognized the potential of avutometinib in combination with defactinib (a FAK inhibitor) by granting it Breakthrough Therapy designation for treating all patients with recurrent low-grade serous ovarian cancer (LGSOC), irrespective of their KRAS status, after one or more prior lines of therapy, including platinum-based chemotherapy. RAMP 201 is a trial aimed at registering avutometinib, either alone or combined with defactinib, in patients with recurrent LGSOC.
RMC-4630 (SAR442720): Revolution Medicines
Phase II
RMC-4630 (also known as SAR442720) is a highly effective small compound intended for oral use, engineered to specifically hinder the function of SHP2. This essential cellular protein regulates cell survival and proliferation by transmitting signals from receptor tyrosine kinases to RAS. Currently, the company is in the Phase II trial stage, investigating the combination of RMC-4630 with sotorasib for individuals with non-small cell lung cancer harboring a KRAS G12C mutation. These patients have not responded to standard therapies and have not previously undergone treatment with an RAS inhibitor. Discover which therapies are expected to grab major KRAS inhibitorsKRAS inhibitors market share @ KRAS InhibitorsKRAS Inhibitors Market Report
BI 1701963: Boehringer Ingelheim
Phase I
BI 1701963 is a compound designed to inhibit the activity of KRAS across various oncogenic variants, particularly targeting major G12 and G13 oncoproteins. Its mechanism involves binding to SOS1, a crucial component in activating KRAS by facilitating the exchange of RAS-bound GDP for GTP. This selective inhibition of SOS1 presents a promising therapeutic approach, enabling KRAS suppression regardless of mutation type. Preclinical studies demonstrate the efficacy of this pan-KRAS inhibitor in impeding tumor growth across numerous tested G12 and G13 KRAS mutations, which are commonly observed in the protein. Additionally, the compound exhibits selectivity towards cancer cell lines bearing mutations in the KRAS gene. Currently undergoing Phase I trials, BI 1701963 is being assessed both as a standalone treatment and in combination with trametinib for patients with advanced or metastatic solid tumors
carrying KRAS mutations. Boehringer Ingelheim has initiated a clinical collaboration with Amgen to explore the potential of BI 1701963 in combination with LUMAKRAS.
Divarasib/GDC-6036: Roche
Phase I
Divarasib/GDC-6036, an orally administered small molecule, exhibited strong and specific inhibition of the KRAS G12C protein in preclinical trials. Engineered to target the switch II pocket of the KRASG12C protein, it interacts specifically with the cysteine at position 12, effectively locking it in an inactive GDP-bound state irreversibly. Results from a Phase Ib study presented at AACR 2023 showed that combining GDC-6036 with cetuximab effectively treated colorectal cancer (CRC), displaying notable clinical efficacy and tolerable safety levels.
LY353798: Eli Lilly
Phase I
LY353798 is a specific covalent blocker of KRASG12C, exhibiting efficacy both alone and when paired with other anti-cancer treatments in preliminary studies. Its pharmacokinetic pro well, prompting its progression to clinical trials. In laboratory settings, LY3537982 has displayed the ability to target the KRAS G12C mutation, hindering mutant KRAS-driven signaling. Phase I clinical trials are underway, focusing on patients with non-small cell lung cancer, colorectal cancer, or other advanced solid tumors. For further information on the most promising KRAS inhibitorsKRAS inhibitors, reach out @ KRAS InhibitorsKRAS Inhibitors Treatment Pipeline
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