Novo Nordisk receives FDA Complete Response Letter for faster-acting insulin aspart – October 7, 2016

In disappointing and surprising news, Novo Nordisk’s next-generation faster-acting insulin aspart has received a Complete Response Letter (CRL) from the FDA. In the announcement, the company shared that the FDA requested additional information related to the immunogenicity and pharmacology assay and that the company is currently evaluating the content of the letter to determine next steps. It’s unclear at this point whether Novo Nordisk will be required to conduct additional clinical studies for the resubmission. We heard from the company that an update on timeline for resubmission, approval, and launch of faster-acting insulin aspart will not likely be ready by the 3Q16 update on October 28. Novo Nordisk will now request a meeting with the FDA regarding the CRL, which will hopefully take place within the next month, though maybe not before the 3Q16 presentation.

Faster-acting aspart is the most advanced of the “next-generation” rapid-acting insulins in the clinical development pipeline and reported full phase 3 results at ADA 2016. Lilly/Adocia’s Ultra-Rapid BioChaperone Lispro recently completed phase 2. As a whole though, the clinical data and profile of the faster-acting new insulins have inspired less excitement than their basal insulin counterparts (we heard commentary to this effect during a panel discussion at CMHC 2016 this afternoon – stay tuned for our report on Monday for more). We also expect the pressures in the rapid-acting insulin landscape will continue to rise in the coming years as the popularity of GLP-1 agonists and SGLT-2 inhibitors grows. That said, it certainly appears that the FDA is tougher than ever on diabetes drug submissions of late – this decision follows a slate of recent delays in FDA decisions for approval of Novo Nordisk’s Xultophy (insulin degludec/liraglutide), approval of Sanofi’s iGlarLixi (insulin glargine/lixisenatide), label expansion of Lilly/BI’s Jardiance (empagliflozin). Faster-acting aspart has also been submitted in the EU, Switzerland, Canada, Brazil, South Africa, and Argentina – an European Medicines Agency (EMA) decision for the product is expected by 1Q17.

Close Concerns Questions

Q: What additional information in particular does the FDA require regarding the immunogenicity assays?

Q: In what ways were the assays highlighted by the FDA as requiring additional information different from assays used in past Novo Nordisk studies?

Q: To what extent does this CRL reflect under-resourcing at the FDA, versus lack of sufficiently compelling data to support faster-acting insulin aspart?

Q: Will the FDA require additional clinical trials to move faster-acting insulin aspart forward?

Q: Presumably Novo Nordisk is in discussions with the FDA on how to proceed. How soon can we expect conclusive answers on the path forward and timeline for faster-acting insulin aspart?

Q: Faster-acting insulin aspart is also under review in the EU, Switzerland, Canada, Brazil, South Africa, and Argentina. Will we see similar setbacks with the EMA and other regulatory bodies?

-- by Helen Gao, Abigail Dove, and Kelly Close