Regulatory authorities in Europe and the US have endorsed the safety of incretin mimetics for diabetes, including the DPP-4 inhibitor (gliptin) class, which have been linked to pancreatic cancer.
The FDA and EMA have taken the unusual step of publishing a review article to set the record straight on the issue, which has been the subject of “intense interest” among the medical profession.
A possible link first emerged from safety studies of incretin mimetics, which also include GLP-1 analogues such as Novo Nordisk’s Victoza (liraglutide), AstraZeneca’s Byetta (exenatide) and Sanofi’s Lyxumia (lixisenatide).
Both regulators started reviewing the safety of the drugs last year after data suggested the drugs may increase the risk of pancreatitis and pancreatic duct metaplasia, a precursor to cancer. The main prompt was a study published by academic researchers that examined a small number of pancreatic tissue specimens taken from patients taking incretin mimetics after they died from unspecified causes.
They reviewed hundreds of animal toxicology studies submitted in support of marketing applications for gliptin and GLP-1 analogue drugs in the US and EU, as well as two cardiovascular outcomes studies for two gliptins, namely AstraZeneca’s Onglyza (saxagliptin) and Takeda’s Nesina (alogliptin).
The EMA made a public statement that it had no safety concerns with incretin mimetics last year, but it seems the two regulators felt a more direct assertion was needed.
“Both agencies agree that assertions concerning a causal association between incretin-based drugs and pancreatitis or pancreatic cancer, as expressed recently in the scientific literature and in the media, are inconsistent with the current data,” they write in the New England Journal of Medicine.
That is not quite the end of the matter, however, as the agencies say their investigation cannot definitively rule out a link and they will continue to monitor post-marketing data for safety signals.
There was also immediate criticism of the stance taken by the FDA and EMA from scientific figures, including the researcher behind the original study, Peter Butler of the University of California Los Angeles (UCLA) and as the Health Research Group of US consumer organisation Public Citizen. Both suggested the conclusions were premature.
The effect of the proposed link to pancreatitis on sales of the incretin mimetics over the last year is hard to quantify, but they feature prominently among the top-selling drugs of 2013, with Merck & Co’s Januvia (sitagliptin) and Victoza both in the top 50 in the US market.
Analysts have suggested that the solid growth rates for many of the drugs in the incretin mimetic class last year suggest any negative impact on sales was likely to be small.