全球 Menin 抑制劑市場：臨床試驗與未來機會 (2023)
Global Menin Inhibitor Drugs Clinical Trials & Future Opportunity Insight 2023
Menin 是新一代蛋白質，已被用作多種疾病，特別是癌症的治療標靶。透過對 1 型多發性內分泌腫瘤 (MEN1) 的研究，menin 蛋白首次與良性腫瘤聯繫起來，現在正在研究其在癌症和糖尿病中的作用，發現在這兩種疾病中都具有潛在的用途。因此，需要開發可用於治療這些疾病的menin抑制劑。儘管尚未批准 Menin 抑制劑，但 menin 抑制劑管道中有多種有前景的候選藥物，每種都有可能成為市場上第一類獲得批准的 menin 抑制劑。
幾種menin抑制劑目前正處於治療白血病的早期臨床試驗中，其中levmenib（以前稱為SNDX-5613）是目前最有前途的候選藥物之一。Revumenib 由 Syndax Pharmaceuticals 開發，是一種高效的 menin 抑制劑，在該公司正在進行的臨床試驗中已顯示出令人信服的臨床特徵。正在進行的 AUGMENT-101 臨床試驗正在評估 levmenib 作為急性白血病的單一療法，而 AUGMENT-102 臨床試驗正在研究 menin 抑製劑與既定的白血病標準治療的協同作用。Wymenib 正在與化療聯合進行測試。
2022年12月，FDA授予levmenib突破性療法認定，用於治療攜帶KMT2A重排的複發性或難治性急性白血病患者。它還獲得了 FDA 的快速通道指定，用於治療患有 NPM1 基因突變的複發性或難治性急性髓性白血病 (AML) 或急性淋巴細胞白血病 (ALL) 的成人和青少年。快速通道指定加快了 FDA 對研究藥物的審查，並可能使 Revumenib 成為第一個獲得上市批准的 menin 抑制劑。在獲得 FDA 指定之前，levmenib 還於 2021 年 12 月獲得 EMA 的孤兒藥物指定，用於治療急性髓性白血病。
“Global Menin Inhibitor Drugs Clinical Trials & Future Opportunity Insight 2023” Report Highlights:
Menin represents a new generation of proteins that have found application as a therapeutic target in several prevalent diseases, especially cancer. First linked with benign tumors through the studies on multiple endocrine neoplasia type 1 (MEN1), the menin protein is now being studied for its role in cancer and diabetes, finding potential use in both. This has generated the need for development of menin inhibitors that can be used to treat these diseases. Though no menin inhibitor has received approval yet, the pipeline of menin inhibitors is populated with multiple promising candidates, each having the potential to become the first-in-class menin inhibitor to receive market approval.
The role of menin inhibitors has been confirmed in multiple cancers, out of which leukemia is dominating the research and development landscape because menin's role in this hematological cancer is the most well characterized out of all indications it has found use in. The menin protein acts as an important cofactor for the fusion proteins of mixed lineage leukemia (MLL) gene, mutations in which are linked to the development of acute leukemia. This association with a prevalent cancer sparked interest in this field and has led to the development of many potential inhibitors.
Several menin inhibitors are now undergoing early phase clinical trials in leukemia, out of which Revumenib, previously known as SNDX-5613, is one of the most promising candidates currently. Revumenib was developed by Syndax Pharmaceuticals, and is a highly potent inhibitor of menin, which has shown a convincing clinical profile in the company's ongoing clinical trials. The ongoing AUGMENT-101 clinical trials is assessing Revumenib as a monotherapy in acute leukemias and the AUGMENT-102 clinical trial is testing Revumenib in combination with chemotherapy to determine the synergized effects of menin inhibitors with established standard of care for leukemia.
The FDA designated Revumenib as a breakthrough therapy in December 2022 the treatment of patients with relapsed or refractory acute leukemia who have a KMT2A rearrangement. In addition, it also has the Fast Track designation from the FDA for the treatment of adults and adolescents with relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) with an NPM1 mutation. The fast track designation expedites the review of investigational drugs by the FDA, which puts forth Revumenib as the potential first menin inhibitor to receive marketing approval. Prior to these FDA designations, Revumenib was also granted the orphan drug designation by the EMA in December 2021 for treating acute myeloid leukemia.
Another candidate that has garnered significant attention is BMF-219, a menin inhibitor developed by Biomea Fusion. BMF-219 made name for itself as the first menin inhibitor to enter clinical trials for the treatment of solid cancers. In contrast to other menin inhibitors in the clinical trials, Biomea has expanded the clinical assessment of BMF-219 to KRAS-driven non-small cell lung cancer, pancreatic cancer, and colorectal cancer. The interaction pathways between menin, KRAS and MYC have been established in research studies, which has allowed for this expansion in clinical trials for BMF-219. The trial is still in early clinical phase with the first patient receiving BMF-219 dosage in January this year.
BMF-219 is also an important menin inhibitor in sense that along with solid cancers, it is also the first menin inhibitor to undergo clinical trial for type 2 diabetes mellitus. The candidate showed glycemic control in patients ever after the treatment was stopped, which has been attributed to disruption of menin activity by the drug. In addition, Biomea has also planned a clinical trial to assess BMF-219 in type 1 diabetes. BMF-219 therefore represents a potential force that may be used to improve treatment outcomes of diabetic patients.
Therefore, menin inhibitors represent a significant breakthrough in the management of some prominent diseases marked by high prevalent rates, high mortality rates and a dearth of effective treatments. Ongoing research has been linking menin activities with several other gene products, which can potentially expand the use of menin inhibitors to several other indications. That being said, the global market for menin inhibitors is still in its nascent stage, with companies like Biomea Fusion and Syndax Pharmaceuticals emerging as pioneers of menin inhibitors research. The market holds immense future potential, both clinically and commercially, which needs to be tapped to exploit this newfound commercial opportunity.