FDA Grants Orphan Drug Designation to Leads Biolabs' LBL-034 for Multiple Myeloma
核心洞察
The FDA has granted Orphan Drug Designation to LBL-034, a bispecific antibody, for treating multiple myeloma (搜索), a rare and life-threatening malignancy.
LBL-034 targets GPRC5D (搜索) and CD3 (搜索), activating T-cells against cancer cells, and has shown promising antitumor efficacy and safety in early clinical results.
A Phase 1/2 clinical trial (NCT06049290) is underway, evaluating LBL-034 in patients with relapsed/refractory multiple myeloma (搜索), with preliminary data expected at the 2024 ASH Annual Meeting.
The FDA has granted Orphan Drug Designation to LBL-034, a humanized, bispecific T-cell engaging antibody developed by Leads Biolabs (搜索), for the treatment of patients with multiple myeloma (搜索). This designation aims to encourage the development of new therapies for rare diseases affecting fewer than 200,000 people in the United States. Multiple myeloma remains an incurable malignancy, and LBL-034 offers a novel approach by targeting GPRC5D (搜索) and CD3 (搜索) to activate T-cells against cancer cells.
Mechanism of Action and Preclinical Data
LBL-034 is designed to bind to both CD3 (搜索) on T cells and GPRC5D (搜索), a tumor-associated antigen expressed on multiple myeloma (搜索) cells. This bispecific interaction leads to T-cell activation and subsequent killing of cancer cells. Preclinical studies presented at the 2023 ASH Annual Meeting & Exposition demonstrated that LBL-034 induced strong T-cell dependent cell killing in GPRC5D-positive cells. The antibody weakly bound to CD3 in the absence of GPRC5D-expressing cells, limiting off-target effects. In vivo studies using the MC38-GPRC5D syngeneic model and NCI-H929 xenograft model showed potent antitumor activity at low doses of 1 mg/kg and 0.3 mg/kg, respectively.
Clinical Development and Early Results
LBL-034 is currently being evaluated in a first-in-human, open-label, multicenter, dose-escalation and dose-expansion Phase 1/2 trial (NCT06049290) in patients with relapsed/refractory multiple myeloma (搜索). The study received investigational new drug application approval from both the Chinese National Medical Products Administration and the FDA in 2023. Early signals of robust efficacy and favorable safety have been observed in the ongoing trial. Preliminary data from the trial are expected to be presented at the upcoming 2024 ASH Annual Meeting & Exposition.
Safety Profile
The toxicology profile of LBL-034 was assessed in cynomolgus monkeys, who received repeated intravenous doses of 5 mg/kg, 15 mg/kg, and 50 mg/kg weekly for up to 5 cycles. The agent was well-tolerated, with a no-observed-adverse-effect-level (NOAEL) of 50 mg/kg based on pharmacology, pathology, and biochemistry analyses.
Significance of Orphan Drug Designation
According to Charles Cai, MD, PhD, CMO of Leads Biolabs (搜索), multiple myeloma (搜索) remains an incurable malignancy, and the interval between tumor relapses shortens with increasing lines of treatment, eventually evolving into relapsed/refractory multiple myeloma. He emphasized the urgent need for new and more effective treatment options. Xiaoqiang Kang, MD, PhD, founder, chairman, and CEO of Leads Biolabs, noted that LBL-034 is the first product from Lead Biolabs to receive orphan drug designation from the FDA, marking a significant milestone for the company. The company aims to further optimize its pipeline and provide innovative solutions for unmet medical needs in the biopharmaceutical field.