Global LAG 3 Inhibitor Clinical Trials and Market Opportunity Insight 2028 Report Highlights:
Cancer immunotherapy is a novel approach which can reverse tumor immune escape by suppressing immune checkpoint pathways. Several immune checkpoint inhibitors targeting cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have demonstrated durable efficacy against melanoma, renal, lung and other cancers. However, despite these promising long-term responses, the majority of patients failed to respond to immune checkpoint blockade, demonstrating primary resistance. Additionally, many of these patients who initially respond to treatment eventually experience relapse secondary to acquired resistance.
To mitigate these challenges, researchers have identified several co-stimulatory receptors including lymphocyte activation gene-3 (LAG-3). LAG-3 is a member of the immunoglobulin superfamily (IgSF) and exerts a wide variety of biologic impacts on T cell function. It is expressed on the cell membranes of natural killer (NK) cells, tumor infiltrating lymphocytes (TIL), a subset of T cells, and dendritic cells. Beyond its role in wide range of autoimmune diseases, it also reduces the body’s ability to resist infection and promote chronic infections. Apart from this, the receptor is also over-expressed in several cancers including breast cancer, melanoma, non-Hodgkin lymphoma, myeloma, gastric cancer, and others.
The receptor is considered as a promising target in cancer immunotherapy. Studies have demonstrated that LAG-3 has synergistic action with PD-1 and PD-L1. Although the exact mechanism is unclear, it is shown that its modulation causes a negative regulatory effect over T cell function, preventing tissue damage, and autoimmunity. LAG-3 and PD-1 are frequently co-expressed and upregulated on tumor-infiltrating lymphocytes (TILs) leading to immune exhaustion and tumor growth. The blocking of LAG-3 not nly improves anti-tumor immune responses but also potentiates other forms of immunotherapy given its different mechanism of action mainly mediated by impeding cell cycle progression.
At present, researchers have developed two inhibitory approaches including LAG-3 Ig fusion proteins (IMP321) and LAG-3 targeting antibodies. IMP321 developed by Immutep is a soluble forms of LAG-3 which upregulates co-stimulatory molecules and increases interleukin (IL)-12 productions to enhance tumor immune responses. Several LAG-3 targeting monoclonal antibodies have been developed which interferes with the LAG-3 interaction between major histocompatibility complex-II molecules expressed by tumor or immune cells, promoting tumor cell apoptosis. To further enhance the efficacy of LAG-3 targeting drugs, researchers have also established several bispecific antibodies which have enhanced efficacy, specificity, and are cost effective.
There are more than 100 ongoing clinical trials for 35 drugs, which are evaluating the role of LAG-3 inhibitors in wide range of cancers. Relatlimab developed by Bristol Myers Squibb is one of promising LAG-3 targeting antibody which was granted priority review by US FDA for the management of melanoma in combination with Nivolumab. The drug is expected to gain entry in market by 2022, which will revolutionize the paradigm of cancer treatment. Apart from this, several preclinical studies are also evaluating the role of LAG-3 in other therapeutic indications including diabetes, multiple sclerosis, HIV, Parkinson, and other autoimmune disorders.
The emerging trend in LAG-3 next generation immunotherapies with continuous headway movement along with new emerging technologies for the development of target therapies argues the hope for better alternative therapies during the forecast period. The growing burden of critical diseases such as cancer, leukemia, lymphoma, and muscular degeneration are the major factors that boost the adoption of LAG3 targeting drugs among the global population. Moreover, rise in number of pipeline drugs and high growth potential in untapped emerging economies is expected to open new opportunities for the market players in future. The key players in the market include MacroGenics, Zai Lab, Bristol-Myers Squibb, Ono Pharmaceuticals, Immutep, Novartis, Merck, F-star Therapeutics, among others.