Nedosiran

The Plainsboro entanglement kicked off when the FDA inspected Novo’s site early last year as part of a review of the company’s compliance with postmarketing adverse drug experience regulations. Amid the company’s efforts to resolve issues raised during an FDA inspection early last year, Novo Nordisk’s operating base in Plainsboro, New Jersey—already the recipient of a recent Form 483—has been hit with the more severe consequence of a Warning Letter. Novo acknowledged the letter, available via the FDA’s website, in its own communique Tuesday, stressing its confidence that it can put the U.S. regulator’s concerns to bed. The Plainsboro entanglement kicked off when the FDA initially inspected Novo’s site, which serves as its U.S. headquarters, from Jan. 13 to Feb. 7 of 2025, as part of a review of the company’s compliance with postmarketing adverse drug experience (PADE) regulations, the FDA explained in its letter. After flagging a number of side effect surveillance and reporting concerns, the agency handed Novo a Form 483 on Feb. 7, 2025, the company said in its press release this week. Novo, for its part, said it has been “working diligently to address those observations ever since,” explaining that it has a corrective and preventive action plan in place and that it has sent the FDA seven updates on its progress since its initial response acknowledging the Form 483. Novo suggested that the warning letter “largely seeks additional details on these measures to confirm current and future regulatory compliance,” adding that the write-up makes no conclusions about the quality or safety of its drugs.  Peeling back the layers on the FDA’s complaints, the regulator began the observations in its letter by stressing Novo’s obligation to develop written procedures to surveil, receive, evaluate and report postmarketing side effects to the agency, singling out products with ingredients like liraglutide, nedosiran sodium, estradiol and semaglutide, the molecule behind Novo’s blockbuster GLP-1 meds Ozempic and Wegovy. Despite the popularity of GLP-1s like Wegovy for weight loss, the class’s hefty side effect burden—primarily gastrointestinal in nature—is well documented. But Novo’s procedures around adverse event tracking have fallen short, the FDA contends in its letter. The FDA’s issues with Novo’s procedures concerned the timing of those adverse event reports to the regulator, a provision that allowed Novo to reject or cancel reports it received and the length of medical reviews related to the reports, among other misgivings. The FDA acknowledged that Novo has taken steps to right the ship at the Plainsboro site, although the regulator said those corrective plans were not detailed enough to determine whether they might prevent similar violations moving forward. In a harsh rebuke of the company, the FDA noted that Novo’s “failure” to identify and assess the root causes of its issues “raises concerns about your firm’s ability to monitor the safety of your products."The FDA added that, “based on the nature of the inspection’s findings and your written response and correspondence, we have serious concerns about the scope and impact of these violations on your entire product portfolio.”For its part, Novo reiterated its confidence in its ability to work through the FDA’s concerns and additionally took time in its press announcement this week to address a string of recent regulatory actions in the U.S. “Novo Nordisk 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 U.S., said in a statement. “We are confident that we will resolve the matters outlined in Warning Letter to the FDA’s full satisfaction.”As for the company’s other recent FDA write-ups, Novo has received a pair of so-called untitled letters related to its marketing of Ozempic and Wegovy, which it says are “being managed,” as well as a separate warning letter at its site in Bloomington, Indiana, that the company snapped up as part of Novo Holdings’ buyout of CDMO Catalent. “We have full confidence that we will be able to holistically and promptly address the matters outlined in each of the Warning Letters,” Novo stressed in Tuesday’s release, referring to the Plainsboro and Bloomington reprimands. Novo’s proactive acknowledgement of its latest warning letter is somewhat uncommon for the industry and may reflect the fact that the Danish drugmaker has had a rough publicity run in recent months.  Ongoing issues at Novo’s Indiana plant—formerly operated by Catalent—have been explicitly tied to several recent FDA drug rejections, including a Complete Response Letter handed down to Incyte’s PD-1 inhibitor Zynyz as a first-line treatment for non-small cell lung cancer last month. While Novo’s purchase of the Bloomington facility is public knowledge, third-party manufacturing sites typically go unnamed when companies and the FDA itself communicate production-influenced drug rejections. But in Novo’s case, CRLs tied to the Indiana plant have led to a string of negative production headlines for the Danish drugmaker.