CDSCO Panel revises warning statement of Sanofi's antidiabetic FDC Insulin Glargine plus Lixisenatide

This came after the drug major Sanofi presented their proposal for revision in the warning statement of the approved drug Fixed Ratio Combination of Insulin Glargine 100U/mL plus Lixisenatide 50 mcg/mL/33mcg/mL from “To be sold by retail on the prescription of an Endocrinologist only” to “To be sold by retail on the prescription of a Registered Endocrinologist or Physician with Post Graduate qualification in Medicine only" or to remove conditions for warning statements.

The insulin glargine and lixisenatide combination is a fixed-ratio combination of a long-acting basal insulin analog and a glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of adult patients with inadequately controlled type 2 diabetes.

Insulin glargine is a modified form of long-acting or basal insulin used to control hyperglycemia in diabetes mellitus. Insulin glargine binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc, and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism.

Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist used in the treatment of type II diabetes mellitus (T2DM).

The activation of the GLP-1 receptor by lixisenatide results in the activation of adenylyl cyclase. This increases the concentration of cyclic adenosine monophosphate in the cell leading to the activation of protein kinase A (PKA) as well as Epac1 and Epac2. PKA, Epac1, and Epac2 are involved the in release of Ca2+ from the endoplasmic reticulum which is known as the "amplification" pathway which increases insulin release when the triggering pathway is activated. By activating this amplification pathway lixisenatide increases glucose-stimulated insulin secretion.

At the recent SEC meeting for endocrinology and metabolism held on 23 November 2023, the expert panel reviewed the proposal presented by the drug major Sanofi for revision in the warning statement of the approved drug fixed-ratio combination of Insulin Glargine 100U/mL plus Lixisenatide 50 mcg/mL/33mcg/mL from “To be sold by retail on the prescription of an Endocrinologist only” to “To be sold by retail on the prescription of a Registered Endocrinologist or Physician with Post Graduate qualification in Medicine only" or to remove condition for warning statement.

After detailed deliberation, the committee recommended revision in the warning statement as “To be sold by retail on the prescription of a Registered Endocrinologist or specialist in Internal Medicine only" subject to the condition that the firm should submit evidence for similar approvals from other global regulatory authorities to CDSCO.

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