Novo Nordisk Inc. – FDA CRL

The FDA issued a Complete Response Letter (CRL) to Novo Nordisk Inc. regarding its Biologics License Applications (BLA) 761326/Original 1 and BLA 761326/Original 2 for NNC0148-0287 injection. The agency determined that the applications cannot be approved in their current form, citing several deficiencies under the BLA regulatory framework.

A primary concern for both applications stems from deficiencies identified during a pre-license facility inspection. Novo Nordisk is required to ensure the facility provides satisfactory responses to the FDA Form 483 findings, including submitting the response dates, with potential for re-inspection.

Specific to BLA 761326/Original 1 for type 1 diabetes, the FDA found an unfavorable benefit-risk balance. Clinical data revealed an unacceptably higher risk of clinically meaningful hypoglycemia (50% higher incidence, 80% higher event rate) compared to a daily basal insulin comparator, without showing superior HbA1c reduction or other patient benefits. This increased risk was linked to the dosing and titration algorithm used in the ONWARDS 6 study.

To address these issues, Novo Nordisk must submit new clinical data demonstrating a favorable benefit-risk profile for NNC0148-0287 in type 1 diabetes patients, and is advised to request a meeting to discuss a new study to optimize dosing. Additionally, a comprehensive safety update and resubmission of the proprietary name are required. Revisions to prescribing information are also pending.