Table 2.

Comparison of Clinical Development and Regulatory Expectations for Different Diabetes Therapies.

	Cell Therapy for Severe T1D	New Onset T1D Immune Therapy	New Insulin Analog
Patient population	Late T1D with disabling hypoglycemia	All with T1D diagnosed within 3 months	Any T1D or T2D requiring insulin treatment
Study design	Single-arm open label	Placebo-controlled	Active-controlled (insulin comparator)
Total N for submission	200	1000	4000
Primary endpoint	Percent of subjects with HbA1c<6.5% and no hypoglycemia	C-Peptide	HbA1c Non-inferiority
Secondary endpoint	Percent off insulin treatment at one year	HbA1c, hypoglycemia, insulin dose	Hypoglycemia rates
Study duration to endpoint	12 months	24 months	26-52 weeks
Long-term follow-up	Important but informal	Strongly encouraged	Only required for a subset
Requirement for CVOT	No	No	Only if a CV signal is detected
FDA Review Center	CBER	CDER	CDER

Abbreviations: T1D, Type 1 Diabetes; T2D, Type 2 Diabetes; CVOT, Cardiovascular Outcome Trial; CV, Cardiovascular; FDA, US Food and Drug Administration; CBER, Center for Biologics Evaluation and Research; CDER, Center for Drug Evaluation and Research