FDA Grants Orphan Drug Designation to LBL-034 for Multiple Myeloma

FDA

The humanized, bispecific T-cell engaging antibody targeting GPRC5D and CD3 LBL-034 has received orphan drug designation from the FDA for the treatment of patients with multiple myeloma.¹

“I am pleased to see the positive progress in our development of the new medications to benefit patients with rare diseases like multiple myeloma. Multiple myeloma remains an incurable malignancy and with the increasing lines of treatment, the interval between the tumor relapses will become shorter and shorter, and eventually it will evolve into relapsed/refractory multiple myeloma, which seriously threatens human life and health,” Charles Cai, MD, PhD, CMO of Leads Biolabs, stated in a news release. “It is urgent to develop new and more effective treatment options. LBL-034 adopts a unique molecular design, and the preliminary clinical results indicate its promising antitumor efficacy and safety. We will expedite the clinical development of LBL-034 and strive to bring safe and effective treatment options to multiple myeloma patients around the world as early as possible.”

The bispecific antibody binds to both CD3 on T cells and the tumor-associated antigen GPRC5D on cancer cells, resulting in T-cell activation against cancer cells. As the third GPRC5D-targeted CD3 T-cell engager to enter clinical development, the agent has shown higher binding affinity for GPRC5D and potency and less T-cell exhaustion and cell death. 

The agent is currently under study 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.1,2 The study, which received investigational new drug application approval from the Chinese National Medical Products Administration on July 20, 2023, and by the FDA on July 28, 2023, was subsequently launched in China in 2023 and demonstrated early signals of robust efficacy and favorable safety.1,3 Preliminary data from the trial are expected to be presented at the upcoming 2024 ASH Annual Meeting & Exposition.¹

In a preclinical study presented during the 2023 ASH Annual Meeting & Exposition, LBL-034 led to strong T-cell dependent cell killing in GPRC5D-positive cells with low to high expression and increased CD25 and CD69 expression and cytokine release of IFN-γ, TNF-α, and IL-6.⁴ Notably, LBL-034 weakly bound to CD3 and had limited effects on cytokine release in the absence of GPRC5D-expressing cells. When LBL-034 was evaluated in the MC38-GPRC5D syngeneic model and NCI-H929 xenograft model potent antitumor activity was seen at the low doses of LBL-034 at 1 mg/kg and 0.3 mg/kg, respectively.

The toxicology profile of LBL-034 was also studied, whereby cynomolgus monkeys received repeated doses of 5 mg/kg, 15 mg/kg, and 50 mg/kg intravenously every week for up to 5 cycles. The safety profile of LBL-034 was well tolerated according to pharmacology, pathology, and biochemistry analyses, and the no-observed-adverse-effect-level of the agent was determined to be 50 mg/kg.

“LBL-034 is the first product from Lead Biolabs to receive orphan drug designation from FDA, marking a successful step for us on this challenging but meaningful journey.¹ Taking this opportunity, we will further optimize our pipeline layout, broaden our exploration boundaries in the biopharmaceutical field, and provide innovative solutions for more unmet medical needs,” Xiaoqiang Kang, MD, PhD, founder, chairman, and CEO of Leads Biolabs, concluded in the news release.

References

1. Leads Biolabs receives orphan drug designation from the US FDA for LBL-034, a uniquely designed, highly differentiated anti-GPRC5D/CD3 bispecific antibody, for the treatment of multiple myeloma. News release. Nanjing Leads Biolabs Co., Ltd. November 6, 2024. Accessed November 6, 2024. https://en.leadsbiolabs.com/Leads-Biolabs-Receives-Orphan-Drug-Designation-from-the-US-FDA-for-LBL-034-a-Uniquely-Designed-Highly-Differentiated-Anti-GPRC5D-CD3-Bispecific-Antibody-for-the-Treatment-of-Multiple-Myeloma-id47365156.html
2. A phase I/II clinical trial of LBL-034 in patients with relapsed refractory multiple myeloma. ClinicalTrials.gov. Updated April 17, 2024. Accessed November 6, 2024. https://clinicaltrials.gov/study/NCT06049290
3. Key preclinical data on LBL-034, a uniquely designed, highly differentiated bispecific antibody targeting GPRC5D will be presented at the 65th American Society of Hematology (ASH) Annual Meeting. News release. Leads Biolabs. December 8, 2023. Accessed November 6, 2024. https://en.leadsbiolabs.com/Key-preclinical-data-on-LBL-034-a-uniquely-designed-highly-differentiated-bispecific-antibody-targeting-GPRC5D-will-be-presented-at-the-65th-American-Society-of-Hematology-ASH-Annual-Meeting-id62538107.html
4. Wang B, Huang X, Sun J, et al. Lbl-034, a highly differentiated T-cell engaging bispecific antibody targeting GPRC5D for the treatment of relapsed or refractory multiple myeloma. Blood. 2023;142(suppl 1):4672. doi:10.1182/blood-2023-181395