Role of LAG 3 InhibitorLAG 3 Inhibitor In Cancer Immunotherapy
10 Jul 2024
LAG-3 (Lymphocyte Activation Gene-3) has emerged as a significant target in cancer immunotherapy, representing a new frontier in the ongoing efforts to harness the immune system to combat cancer. First discovered in 1990, LAG-3 is a cell surface molecule that plays a crucial role in regulating T cell function and has been identified as an important immune checkpoint. Following this, the approval to worldwide first LAG-3 inhibitorLAG-3 inhibitor therapy; Opdualag™ (nivolumab and relatlimab-rmbw), developed by Bristol Myers Squibb, in March 2022, for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma, further aid to expand the realm as well as competitve landscape. According to Neeraj Chawla, Research Head at Kuick Research, the global market opportunity for LAG 3 drugs will surpass US$ 3 Billion by 2029 and more LAG 3 drugs are expected to enter the market by end of this decade.
From clinical perspective, LAG-3 has garnered significant attention as a potential target for cancer immunotherapy. It has been found to synergize with other immune checkpoints, such as PD-1 and CTLA-4, to enhance immune evasion by tumors. This understanding has led to the development of LAG-3 inhibitorsLAG-3 inhibitors, including monoclonal antibodies that block LAG-3 and restore T cell function. Several of these inhibitors are currently undergoing clinical trials, both as monotherapies and in combination with other immune checkpoint inhibitors, showing promising preliminary results in terms of safety and efficacy across various cancer types, including melanoma, non-small cell lung cancer, and renal cell carcinoma.
As well as, commercially, the LAG-3 inhibitorLAG-3 inhibitor market is poised for growth due to augmenting triumph of approved therapy whose sales have increased twice and has crossed half a Billion-dollar sales in 2023; representing opportunism to come in pharma sector. Additionally, the potential for combination therapies that include LAG-3 inhibitorsLAG-3 inhibitors offers significant commercial opportunities, as these combinations may provide superior clinical outcomes compared to monotherapies.
For that reason, many clinical trials are ongoing in the domain in order to understand the role of LAG-3 in cancer. For instance, ABL Bio, a Biotech company based in South Korea, has begun a first-in-human (FIH) phase 1 open-label, multicenter, multiple-dose, dose-escalation and dose-expansion study of ABL501 to evaluate the safety, tolerability, MTD and/or RP2D, PK, immunogenicity, preliminary anti-tumor activity, and the PD effect of ABL501 in subjects with any progressive locally advanced (unresectable) or metastatic solid tumors. It is an interventional study (NCT05101109) which has an estimated enrollment of 36 participants, begun in October 2021 and will be completed by December 2024.
Accompanied with clinical trials, many preclinical contenders targeting LAG-3 have been developed. Like, Y Biologics has developed a novel, cutting-edge mono- specific LAG-3 therapy, YBL-011 which is currently in the preclinical stage for the treatment of solid tumors. Above this, the global interest in LAG-3 therapies is influencing immunotherapy market, as multinational pharmaceutical companies seek to collaborate with local firms and tap into the advanced research capabilities available in the global segment. This international collaboration not only enhances the technological exchange but also opens up the new investment and growth opportunities.
Such as, in June 2024, Immutep, an Australian based company, announced that it has settled into a clinical trial collaboration as well as supply agreement with Merck through a subsidiary with the foremost obejctive to access eftilagimod alfa (efti) in combination with anti-PD-1 therapy, Keytruda (pembrolizumab) along with chemotherapy for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in a pivotal Phase III trial.
In nutshell, targeting LAG-3 in cancer therapy represents a promising avenue for enhancing anti-tumor immune responses and overcoming resistance to current immunotherapies. The ongoing clinical trials in addition to robust commercial interest underscore the potential impact of LAG-3 inhibitorsLAG-3 inhibitors in the evolving landscape of cancer treatment, although continued research and clinical validation are essential to fully realize their therapeutic potential.
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