The Importance of C-Peptide for Developing T1D Disease-Modifying Therapies

Area of Science:

• Endocrinology
• Immunology
• Clinical Pharmacology

Background:

• Type 1 diabetes (T1D) involves progressive beta-cell destruction, impacting insulin production.
• Preserving beta-cell function in T1D correlates with better clinical outcomes, including glycemic control and reduced complications.
• Current T1D interventions cannot halt beta-cell destruction post-diagnosis.

Purpose of the Study:

• To advocate for the reinstatement of C-peptide as a primary endpoint for regulatory approval of T1D therapies.
• To highlight C-peptide's role in facilitating faster development and accessibility of disease-modifying treatments.

Main Methods:

• Review of regulatory policies and historical use of C-peptide as a clinical endpoint.
• Analysis of C-peptide's reliability and feasibility as a measure of endogenous insulin secretion.
• Discussion of the impact of endpoint selection on therapy development timelines and investment.

Main Results:

• C-peptide is the most reliable and feasible measure of endogenous insulin secretion in T1D.
• The U.S. Food and Drug Administration (FDA) previously accepted C-peptide as an endpoint from 2008-2023.
• The reasons for C-peptide's recent exclusion from the FDA's Surrogate Endpoint Table are unclear.

Conclusions:

• Reinstating C-peptide as a regulatory endpoint would significantly expedite the availability of new T1D therapies.
• A C-peptide-based policy could stimulate investment in T1D research and development.
• This change would ultimately improve clinical outcomes and reduce the burden for individuals with T1D.