Late Monday afternoon Merck released the top line results of TECOS, the cardiovascular outcomes trial with its blockbuster diabetes drug Januvia (sitagliptin). The company said that the trial “achieved its primary endpoint of non-inferiority for the composite cardiovascular (CV) endpoint.” Merck announced only one additional detail: “Among secondary endpoints,” they reported, “there was no increase in hospitalization for heart failure in the sitagliptin group versus placebo.”
The FDA has been wrestling for a number of years now with the problem of the cardiovascular effects– whether positive or negative– of diabetes drugs. The first large outcomes trials with two other DPP-4 inhibitors, saxagliptin (Onglyza, AstraZeneca) and alogliptin (Nesina, Takeda Pharmaceuticals) were reported in 2013 and found no impact of the drugs on cardiovascular outcomes.
However, a troubling signal emerged suggesting a possible raised risk for heart failure, though the endpoint was not rigorously studied in the trials. Two weeks ago the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee reviewed the trials and rejected recommendations from critics for new restrictions on their use, but they did say that information from the two clinical trials should be added to the drugs’ labels.
In a research note Bernstein analyst Timothy Anderson wrote that the TECOS news removes “a psychological overhang” from the drug and leaves Januvia as “the best-positioned DPP4 in the category,” which may allow it to “pick up at least some market share from its direct competitors.”
At this point, however, some caution may be warranted. Even when the data do become available it bears remembering that without direct comparisons of the drugs any conclusions about differences between the drugs should be considered highly speculative. The only thing known for sure at this point is that all three drugs have been shown to have a neutral effect on cardiovascular outcomes.
Sanjay Kaul, a frequent FDA advisor, pointed out the paradox of the large commercial success of the diabetes drugs despite the absence of any proven clinical benefit:
“So, we have a drug that yields modest glycemic efficacy, is neutral with respect to cardiometabolic factors (lipids, weight, blood pressure), does not kill you or land you in a hospital, and yet is a blockbuster drug nearly 5 times over! What is the big news here? That it does not kill you or land you in a hospital? Or that it is a blockbuster drug nearly 5 times over without evidence of microvascular or macrovascular outcome benefit? Miracle of medicine or miracle of marketing?”
Source: Forbes Health