Invokana Lawsuit: Cardiovascular Safety Concerns Were Expressed Early On

Invokana Lawsuit: Cardiovascular Safety Concerns Were Expressed Early On

Much of the recent bad news surrounding the new “miracle” diabetic drug Invokana (canagliflozin) has to do with a condition known as ketoacidosis, which can cause a dangerous rise in blood acidity. This in turn can lead to coma and even death. However, there is another increasingly apparent problem with this drug; and there is powerful evidence that both the drug maker and the FDA were aware of it. That issue is the risk of Invokana myocardial infarction (heart attacks).

In January 2013, there was a meeting of the FDA Endocrinologic and Metabolic Drugs Advisory Committee (EMDA), where representatives of Janssen Pharmaceuticals (drug maker Mitsubishi Tanabe's U.S. marketing partner) gave several presentations on the growth of Type 2 diabetes among the population, the need for effective treatments (as opposed to more focus on prevention), and of course, the wonders of its latest product, Invokana. During the question-and-answer session that followed, a physician by the name of Dr. Sidney Wolfe – co-founder and director of Public Citizen's Health Research Group – raised serious questions. Pointing out that Janssen's request for FDA approval was “based solely on surrogate efficacy of HbA1c lowering” (a measure of how well a patient's blood sugar is controlled). Dr. Wolfe said:

As with all recently approved Type 2 diabetic drugs, [there is] no evidence of any improved clinical outcomes, contrary to an older diabetes drug such as metformin . . . this surrogate efficacy needs to be balanced against a number of serious safety signals identified in the clinical trials.

His primary concern was “thrombotic events” (blood clots) that could lead to heart attacks. He pointed out that in the studies presented, thirteen subjects on Invokana experienced “cardiovascular events.” Taking available data from a related drug of the gliflozin class, Farxiga (dapagliflozin), he extrapolated data in order to demonstrate that the risks for Invokana heart attack would be significantly greater: “there is much more of an increase in hematocrit in the people getting canagliflozin [Invokana], 1.5 times as much as the dapa [gliflozin] group,” Dr. Wolfe state.

Hematocrit refers to the concentration of red blood cells, which is increased by gliflozin drug’s mechanism of action. Normal concentration is 40% for women and 45% for men; levels higher than this increases the likelihood that the patient will develop a blood clot, causing stroke or heart attack. According to Dr. Wolfe, at least 25% of patients on Invokana would wind up with a red blood cell concentration of 47% - which he described as “a very dangerous range.”

Additionally, FDA Reviewer Dr. Hyon Kwon testified at the committee hearing that there was “an imbalance in early cardiovascular events” observed in the CANVAS trial, a 4,300-subject study assessing the cardiovascular effects of Invokana.  When FDA Biostatistician Dr. Mat Soukop testified, it became apparent how profound this “imbalance” is.  Dr. Soukop testified that, in the first 30 days of use, Invokana had a cardiovascular events “Hazard Ratio” of 6.9; that is, patients who were taking Invokana had a 690% higher likelihood of suffering a cardiovascular event than the patients who were taking a placebo.

With Dr. Wolfe's expert testimony and the FDA’s own biostatistical analysis, it would be assumed that Janssen and Mitsubishi Tanabe would have been ordered to conduct further studies before the FDA approved the drug to be administered to patients in the United States. Instead, the FDA gave approval for sales of Invokana, but on the condition that the company monitor its own product for adverse events. Janssen was also ordered to conduct a “post-market” double-blind study in order to determine how many patients actually experienced Invokana heart attacks – and gave Johnson & Johnson's subsidiary four years in which to do it.

Of course, the official position of the FDA is that such decisions are based on analyses of risks versus benefits. But apparently, they ignored the advice of a prominent physician and researcher who clearly demonstrated and stated there was “no evidence of any improved clinical outcomes.”

Attorney Tim O’Brien, an Invokana lawsuit lawyer with Levin Papantonio, has assembled a team of medical experts who have indicated to him that the diabetic ketoacidosis cases foreshadow the more serious injury cases associated with Invokana:  “With so many cardiovascular events occurring so soon after the commencement of Invokana therapy in the CANVAS trial, it is Levin Papantonio's opinion that this drug will end up causing heart attacks and taking lives.”