FDA warns of higher amputation risk for J&J's Invokana

Dive Brief:

  • Johnson & Johnson's type 2 diabetes medicine Invokana (canagliflozin) will now be required to carry a black box warning for an increased risk of foot and leg amputations, the Food and Drug Administration said Tuesday in a safety alert posted to its website. 
  • Results from two clinical trials, including J&J's large cardiovascular outcomes study CANVAS, showed foot and leg amputations occurred about twice as frequently in patients receiving canagliflozin as those on placebo.
  • The FDA's warning covers Invokana along with two other formulations, Invokamet and Invokamet XR, which also contain canagliflozin as an active ingredient. 

Dive Insight:

The FDA had previously warned of the higher amputation risk to canagliflozin in May 2016, but had held off on any label changes while it continued to investigate. Tuesday's alert concludes canaglifozin was a cause of the increased risk and updates the drug's label with new warnings. 

In the CANVAS study, risk of amputation over a year was calculated to be equivalent to 5.9 out of every 1,000 patients treated with canagliflozin products, compared to 2.8 out of every 1,000 patients treated with placebo.

A similar uptick in risk was seen in the CANVAS-R trial, which studied the effects of canagliflozin on renal function in adults. 

Invokana's label also includes a warning for acute kidney injury, which was added last summer after more than 100 confirmable reports of kidney injury from treatment with Invokana or AstraZeneca's Farxiga (dapagliflozin) were reported to the FDA between March 2013 and October 2015. 

Invokana is part of a class of diabetes drugs known as SGLT-2 inhibitors, which cause the kidneys to remove sugar from the body through urine and thereby lower blood sugar levels in patients with diabetes.

Faster sales growth is expected from the drug class, which also includes AstraZeneca's Farxiga and Eli Lilly and Boehringer Ingelheim's Jardiance (empagliflozin). AstraZeneca is testing Farxiga in its own 17,000-patient cardiovascular outcomes trial, dubbed DECLARE. 

The optimism around that class stems, in part, from expectations of a cardio-protective benefit for SGLT-2 inhibitors. A study sponsored by Lilly and Boehringer known as EMPA-REG found Jardiance reduced the risk of cardiovascular events such as heart attack and stroke by 14% and CV-related deaths by 38%.

So far in 2017, Farxiga has seen a substantial boost in sales, which totaled $207 million over the first three months of the year. Invokana earned $284 million over the same period, but that was down nearly 13% from a year previous due to higher discounts and a greater number of treated patients covered by Medicaid. 

It not yet clear what effect the new warnings may have on Invokana's position versus Farxiga or Jardiance. 

Patients are advised to seek medical attention if they experience pain or tenderness, sores or infections in the legs and feet.  Healthcare professionals should assess a patient's risk factors for amputation, such as peripheral vascular disease or neuropathy, before starting treatment, the FDA recommended. 

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Filed Under: Regulatory / Compliance Marketing