Nanjing Leads Biolabs Co., Ltd. has announced that its anti-PD-L1/4-1BB bispecific antibody, LBL-024, has received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for the treatment of neuroendocrine cancer. This follows a Breakthrough Therapy Designation granted to LBL-024 by China's Center for Drug Evaluation (CDE) of National Medical Products Administration (NMPA). The FDA grants ODD to encourage the development of drugs for rare diseases, offering incentives such as tax credits, FDA guidance, and market exclusivity.
Clinical Data and Potential Impact
Dr. Charles Cai, chief medical officer of Leads Biolabs, highlighted that clinical data to date has been very encouraging, suggesting that LBL-024 could meaningfully improve outcomes for patients with advanced extrapulmonary neuroendocrine cancer. The clinical data demonstrate that LBL-024 monotherapy has more than doubled both the Objective Response Rate (ORR) and Overall Survival (OS) compared to existing treatments for this disease. Based on these results, LBL-024 has entered a single-arm pivotal trial for extrapulmonary neuroendocrine carcinomas in July 2024.
Mechanism of Action
LBL-024 is a tetravalent bispecific antibody that simultaneously targets PD-L1 and 4-1BB. It blocks the PD-1/PD-L1 pathway, lifting immune inhibition, and selectively co-stimulates 4-1BB in the tumor microenvironment, intensifying T cell activation. This dual function synergistically enhances the anti-tumor immune response.
Regulatory and Development Milestones
LBL-024 received IND approvals from both the FDA and NMPA in July and September 2021, respectively, to conduct phase I/II clinical research. According to Frost & Sullivan, LBL-024 is the globally first 4-1BB-targeted drug candidate to have reached pivotal stage.
Neuroendocrine Carcinoma (NEC) Overview
Neuroendocrine carcinoma (NEC) is a class of poorly differentiated, high-grade neuroendocrine neoplasm that originates in the diffuse neuroendocrine cell system. NEC can be divided into pulmonary NEC (including small cell lung cancer (SCLC) and pulmonary large cell neuroendocrine carcinoma (p-LCNEC)) and extrapulmonary NEC. In the United States, there are approximately 127,652 new cases of NECs each year, meeting the FDA's definition of a rare disease. The 5-year survival rate of pulmonary NECs is 5.6%, digestive tract NECs is 13.1%, and other primary NECs is 26.0%.
Implications of Orphan Drug Designation
The ODD provides several benefits, including tax credits for clinical trial expenses, specific guidance from the FDA, exemption of the application fee for new drug registration, and seven years of market exclusivity after listing. Dr. Xiaoqiang Kang, founder, chairman and CEO of Leads Biolabs, noted that this designation enables LBL-024 to receive additional policy support and resource allocation during its development, accelerating its path to market and positioning it as a potential first-in-class therapeutic antibody targeting 4-1BB worldwide.
