CDSCO Approves Levim Lifetech's Phase I/III Trial for Teriparatide Biosimilar in Osteoporosis
核心洞察
The Central Drugs Standard Control Organisation (CDSCO (搜索)) panel has granted approval for Levim Lifetech (搜索)'s Phase I/III clinical trial of a biosimilar teriparatide product for osteoporosis (搜索) treatment.
The approval came after the company submitted a revised clinical trial protocol addressing earlier regulatory observations from the SEC Endocrinology & Metabolism committee.
The multicentric, randomized trial will evaluate the efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics of the biosimilar against Eli Lilly's reference product Forteo®.
The Central Drugs Standard Control Organisation (CDSCO (搜索)) panel has approved Levim Lifetech (搜索)'s Phase I/III clinical trial for a biosimilar teriparatide product, marking a significant step forward in expanding treatment options for osteoporosis (搜索) patients in India. The approval follows the company's submission of a revised clinical trial protocol that addressed earlier regulatory observations.
Regulatory Pathway and Protocol Details
The recommendation was made following the SEC (Endocrinology & Metabolism) observation dated 09 October 2025, after which Levim Lifetech (搜索) submitted a revised clinical trial protocol for the biosimilar teriparatide product. The approved study is titled "A Prospective, Randomized, Assessor-blinded, Multicentric, Parallel Group Phase-I/III Clinical Study to Evaluate the Efficacy, Safety, Immunogenicity, Pharmacokinetics and Pharmacodynamics of Biosimilar Teriparatide of Levim Lifetech Pvt. Ltd. with Reference Product (Forteo® of Eli Lilly) in Subjects with Osteoporosis (搜索) at High Risk of Fracture" under protocol number ICS/LEV/2025-006, Version 2.0 dated 27 October 2025.
The initial protocol submission required revisions to meet regulatory standards. The committee had recommended incorporating several key changes including clearly defining DXA outcome parameters, ensuring DXA reports are evaluated by qualified endocrinologists, re-evaluating inclusion and exclusion criteria for greater objectivity, clearly addressing safety assessments including antidrug antibodies, and providing objective definitions of protocol violations.
Teriparatide's Therapeutic Mechanism
Teriparatide is a recombinant parathyroid hormone (PTH) analog and a potent osteoanabolic agent composed of the first amino(N)-terminal 34 amino acids of human PTH. First approved in the United States in November 2002 and in Europe in April 2003, teriparatide represents the first approved drug in a new category of osteoporosis (搜索) therapy called anabolic therapy for treating osteoporosis in both men and women.
The drug's mechanism of action centers on parathyroid hormone's role as an endogenous hormone that regulates calcium and phosphate metabolism in bone and kidney. PTH regulates bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption by binding to PTH receptors. Importantly, PTH's effects depend on the dose and pattern of exposure to bone - while continuous exposure promotes bone resorption, intermittent exposure to low-dose PTH can induce bone formation more favorably than bone resorption.
Molecular Pathways and Bone Formation
Teriparatide's skeletal effects depend upon the systemic exposure pattern. Once-daily administration stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferentially stimulating osteoblastic activity over osteoclastic activity. The drug mediates its osteoanabolic actions by binding to the N-terminal moiety to PTH type 1 receptors (搜索) (PTH type 1R), which are G-protein coupled receptors expressed on various cells, including osteoblasts, osteocytes, and renal tubular cells.
Binding of teriparatide to PTH receptors on osteoblasts activates downstream PKA- and PKC-dependent signaling pathways that promote anabolic effects on bone. The drug increases expression of pro-osteoclastogenic cytokines like receptor activator of nuclear factor kappa-B ligand (RANKL (搜索)) and macrophage colony-stimulating factor. It also upregulates transcriptional expression of pro-osteoblastogenic growth factors like insulin-like growth factor 1 (IGF1) and fibroblast growth factor 2 (FGF2). Additionally, teriparatide downregulates the synthesis of sclerostin (搜索), a negative regulator of bone formation, while promoting osteoblast differentiation.
Clinical Trial Implications
The approval of this biosimilar trial represents an important development for osteoporosis (搜索) treatment accessibility. The Phase I/III design will comprehensively evaluate the biosimilar's performance across multiple parameters including efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics compared to Eli Lilly's reference product Forteo®. The multicentric, randomized, assessor-blinded, parallel group design ensures robust data collection for regulatory decision-making.
After detailed deliberation, the committee recommended granting permission to conduct the Phase I/III clinical trial as per the revised protocol presented by the firm, setting the stage for potential expanded treatment options for patients with osteoporosis (搜索) at high risk of fracture.