CDSCO Panel Seeks Key Changes in Lupin's Phase III Trial of Biosimilar Insulin Degludec
New Delhi: The Subject Expert Committee (SEC) under the Central Drugs Standard Control Organisation (CDSCO) has opined the drug major Lupin Limited to revise the proposed Phase III clinical trial protocol for its biosimilar Insulin Degludec (rDNA origin) injection 100 IU/mL, intended to be supplied in 3 mL cartridges and pre-filled pens.
The recommendation was made during the SEC (Endocrinology & Metabolism) meeting held on August 6, 2026, following the company’s presentation of Phase I pharmacokinetic/pharmacodynamic (PK/PD) study results and its proposal to conduct a Phase III clinical trial.
In light of earlier SEC recommendation dated 22.05.2026, the firm presented the results of phase I (PK/PD study) along with proposal to conduct Phase III clinical trial titled “A Multi-Centre Randomised, Open Label, Parallel Group, Active Controlled Phase III study to establish the Non-inferiority of Biosimilar Insulin Degludec Injection (rDNA origin) 100 IU/mL to Reference Insulin Degludec Injection (Tresiba) in the Treatment of Type 2 Diabetes Mellitus” vide Protocol No. ECTS/24/010 Version No. 00 dated 17.10.2024.
Insulin Degludec Injection (rDNA origin) is an ultra-long-acting basal insulin used to improve blood sugar control in people with diabetes. The proposed Lupin product is intended to demonstrate non-inferiority to the reference insulin degludec product, Tresiba, in patients with type 2 diabetes mellitus.
Insulin and insulin analogs, such as insulin degludec and insulin aspart, regulate glucose metabolism. By stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting glucose production in the liver, insulin and its analogs reduce blood glucose levels. Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis.
When injected into the subcutaneous tissue, insulin degludec forms multihexamers that result in a subcutaneous depot of insulin degludec. Overall, 2 phenomena contribute to its protracted time-action profile—(1) delayed absorption of insulin degludec from the subcutaneous tissue into the systemic circulation, and (2) binding of insulin degludec to circulating albumin.
After detailed deliberation, the Committee recommended the firm to incorporate following changes in the protocol:
1. The duration of treatment should be extended to 24 weeks.
2. The rescue therapy criteria should be clearly defined.
3. Ophthalmological assessments/ investigations should be included in the study protocol.
4. The protocol should clearly specify the permitted concomitant anti-diabetic medications to be used during the trial.
5. The protocol should clearly define the schedule and time points for anti-drug antibody (ADA) sample collection, the validated methodology for antibody testing, the criteria for repeat testing, and the assessment of neutralizing antibodies.
6. The protocol should clearly specify the exclusion of subjects with conditions predisposing to hypoglycaemia, including, but not limited to, adrenal insufficiency, hypopituitarism, other endocrine disorders associated with hypoglycaemia, and recent or ongoing glucocorticoid therapy or withdrawal, as applicable.
The SEC has accordingly asked Lupin Limited to submit the revised clinical trial protocol to CDSCO for further evaluation by the expert committee.
