Novo rapped by FDA for not reporting drug adverse effects

Novo Nordisk has been sent a warning letter from the FDA for a series of violations of postmarketing adverse drug experience (PADE) regulations, including failure to report side effects among patients using its GLP-1 drugs for diabetes and weight loss.

The latter, addressed to Novo Nordisk's US president David Moore, refers to "objectionable conditions" at the company's facility in Plainsboro, New Jersey, that was inspected as part of the regulator's Bioresearch Monitoring Programme (BIMO), designed to ensure that companies submit "accurate, reliable, and timely safety data" on their products.

Among the violations, according to the FDA, was a failure to develop written procedures that ensured all adverse drug experiences (ADEs) that are the subject of 15-day alert reports were promptly investigated in accordance with regulations.

It also identified incidences in which "serious and unexpected" ADEs were rejected or cancelled if the reporter concluded that it was unrelated to the Novo Nordisk product.

The letter refers specifically to semaglutide, the GLP-1 ingredient in Novo Nordisk's Ozempic for diabetes and Wegovy for obesity. It also cites the company's older GLP-1 liraglutide, which is sold as Victoza for diabetes and Saxenda for weight management, as well as primary hyperoxaluria therapy nedosiran sodium (Rivfloza), and hormone replacement therapy oestradiol.

It says Novo Nordisk did not follow appropriate procedures in reporting three deaths among patients prescribed semaglutide, due to a missing patient identification number, a consent issue, and a link to depression in one case involving a suicide. A stroke in a patient receiving liraglutide also went unnotified. There is no suggestion that the ADEs were linked to treatment with the products.

"FDA relies on the complete, accurate, and timely submission of ADEs to monitor a product's safety profile and uphold FDA's mission to protect and promote public health," said the letter.

"Reporting ADEs to FDA within the required time frames is necessary for the ongoing monitoring of drug safety profiles," it added. "Failure to report and investigate ADEs may limit the safety information that FDA may need when monitoring potential safety signals."

While it acknowledges efforts by Novo Nordisk to implement corrective and preventive measures to address the deficiencies, these were deemed inadequate. In a statement, the company said it "takes PADE reporting requirements seriously and we plan to address the requests in the Warning Letter expeditiously and holistically."

Anna Windle, head of clinical development, medical and regulatory affairs at Novo Nordisk US, said the company is "confident that we will resolve the matters outlined in warning letter to the FDA's full satisfaction."

The company has also received letters from the FDA taking issue with advertising campaigns for Ozempic and Wegovy.