RET Inhibitor Market: Competitive Landscape, Pipeline, and Market Analysis 2024

RET is an abbreviation for "rearranged during transfection", as the DNA sequence of this gene was originally found to be rearranged within a 3T3 fibroblast cell line following its transfection with DNA taken from human lymphoma cells. The human gene RET is localized to chromosome 10 and contains 21 exons. The RET proto-oncogene encodes a receptor tyrosine kinase; RET loss of function mutations are associated with the development of Hirschsprung's disease. while gain of function mutations are associated with the development of various types of human cancer, including medullary thyroid carcinoma, multiple endocrine neoplasia type 2A and 2B, pheochromocytoma, and parathyroid hyperplasia.

Mechanism of action (MOA) of RET Inhibitor is RET inhibitors are targeted therapies that act on tumors with activating alterations in the RET proto-oncogene, such as point mutations or fusions. They fall under the category of tyrosine kinase inhibitors, which work by inhibiting proteins involved in the abnormal growth of cancer cells. RET Inhibitor is used in the treatment of lymphoma, leukemia, sarcoma, carcinoma, endocrine system disorder, glioblastoma, bronchial neoplasm, digestive system neoplasm, immunoproliferative disorders, hematologic disorders, breast diseases, genital diseases, etc. Increased prevalence of autoimmune disorders and various cancers are the key drivers for the RET Inhibitor market. For instance, according to the World Cancer Research Fund International 2020, there were an estimated 18.1 million cancer cases around the world in 2020; of these, 9.3 million cases were in men and 8.8 million in women. The introduction of newer products by market players may look for opportunities that have a big impact on comprehensive research and development in RET inhibitors. For instance, Merck’s Keytruda (Pembrolizumab) was launched for the treatment of endometrial carcinoma. Moreover, to address the difficulties in therapy, numerous market participants are developing innovative compounds. For instance, Takeda’s Motesanib (AMG 706) for the indication of non-small cell lung cancer is under the various stages of clinical studies.

Key Market Developments:

• In September 2020, Blueprint Medicine’s Gavreto (Pralsetinib) has received FDA approval for the treatment of RET fusion-positive non-small cell lung cancer and RET-mutant medullary thyroid cancer.
• In January 2021, Exelixis’s Cabometyx (Cabozantinib) received FDA approval for the additional indication for use in combination with Opdivo (nivolumab) for the first-line treatment of advanced renal cell carcinoma.
• In March 2022, Merck’s Keytruda (Pembrolizumab) received FDA approval for the additional indication in MSI-H or dMMR-positive unresectable or metastatic advanced endometrial carcinoma.

Approved Drug Molecules and Brand Names for RET Inhibitor:

•  Sutent (Sunitinib)
•  Focus V (Anlotinib)
•  Stivarga (Regorafenib)
•  Caprelsa (Vandetanib)
•  Iclusig (Ponatinib)
•  Balversa (Erdafitinib)
•  Retevmo (Selpercatinib)
•  Gavreto (Pralsetinib)
•  Cabometyx (Cabozantinib)
•  Retevmo (Selpercatinib)
•  Gavreto (Pralsetinib)
•  Keytruda (Pembrolizumab)
•  Lenvima (Lenvatinib)
•  Balversa (Erdafitinib)
•  Alecensa (Alectinib)
•  Iclusig (Ponatinib)
•  Cometriq (Cabozantinib)
•  Caprelsa (Vandetanib)

Drugs under the Pipeline for RET Inhibitor:

• Sitravatinib (MGCD516)
• Motesanib (AMG 706)
• HA121-28
• Agerafenib (RXDX-105)
• AUR-109
• EP0031
• LOXO-260
• Luxeptinib (CG-806)
• APL-102
• APS03118
• BTG-002814
• FHND5071
• HEC169096
• HS-10365
• HS269
• JNJ-26483327
• SKI-G-801
• SY-5007
• SYHA1815
• TPX-0046
• TY-1091
• Vepafestinib (TAS0953)

Clinical Activity and Developments of RET Inhibitor:

Up until June 2023, there will be about 46 companies with over 35 compounds that focus on various forms of cancer diseases and endocrine diseases. For these molecules, more than 1,337 clinical trials are being conducted and the majority are in phase-2 and phase-3 clinical trials by the players across the globe. For instance,

• In December 2020, Servier completed phase 2, a randomized study with r-dhap +/- Bortezomib as induction therapy in relapsed/refractory diffuse large b-cell lymphoma (DLBCL) patients eligible for transplantation consisting of Fotemustine drug.
• In September 2022, PharmaMar completed phase 4, Non-interventional Study to Investigate Efficacy and Safety of Yondelis (Trabectedin) in Patients With Advanced Soft Tissue Sarcoma.