Januvia 'misbranded' as Merck keeps silent on post-marketing violation
This article was originally published in Scrip
Merck & Co continues to remain silent on why it seems to have become the latest company to have ignored the deadlines imposed by the US FDA for submitting addition information following a for a US FDA post-marketing requirement to conduct a three-month, pancreatic safety study on a diabetic rodent model treated with its first-in-class DPP-4 inhibitor Januvia (sitagliptin).
The FDA, on 17 February, issued a warning letter to the company relating to sitagliptin and a combination product, Janumet (sitagliptin plus metformin) stating that Merck's violation of this post-marketing requirement meant that the drug is considered "misbranded".
In its response to the letter, Merck said it "is fully committed to complying with the FDA's requirement and is confident that the company will complete the requirement within the time frame outlined in the 17 February letter. Specifically, Merck will submit a final protocol for a new rodent study to the FDA for review within 30 days of the date of the letter, revise it as necessary to gain the FDA's agreement on the new study, and start the study within six months. Merck is preparing its response to the FDA now, including the design of the new study."
However, the issue dates back as far as September 2009, when the FDA revised the labelling of the diabetes drugs, in light of evidence that they may carry a risk of acute pancreatitis – 88 cases of pancreatitis were reported in patients treated with Januvia or Janumet over a prior 2.5 year period from late 2006, when the drug was approved in the US. 66% of these patients were hospitalised, and around half of the cases resolved once treatment was discontinued.
At the time, Merck played down the reports, noting that it already voluntarily added pancreatitis to the post-marketing adverse events section of the products' labelling in the prior March and denied that there was cause for concern (scripintelligence.com, 29 September 2009).
But the FDA was not convinced and the post-marketing requirement was included as part of the agency's February 2010 approval of supplemental new drug applications for Januvia and Janumet; the required study was to have been completed and submitted to FDA by 15 June 2011.
In response to Scrip's questions on why it has not, so far, submitted the requested study to the FDA and why it did not negotiate extended timelines with the agency to address the delay, Merck repeated what was already stated on its website:
"Merck has been providing information to the FDA on its efforts. In December 2009, Merck proposed using data from a completed rodent study to fulfil the PMR. Subsequently, after FDA raised concerns about the adequacy of that data, Merck provided a description to the FDA of a one-year pancreatic safety study in rodents with sitagliptan, which was conducted by independent investigators. Merck subsequently submitted final results from this study to the FDA; however, the FDA informed Merck that what was submitted does not satisfy the PMR, and directed Merck to conduct a new three-month rodent study. As our statement notes, Merck is fully committed to complying with the FDA's requirement and is confident that the company will complete the requirement within the time frame outlined in the letter. Merck takes its responsibility to comply with FDA regulations very seriously, and is thoroughly reviewing its processes and procedures to ensure that Merck fulfils its commitments to the FDA going forward."