UPDATED: J&J's Invokana under scrutiny in EU for potential link to toe amputations

Johnson & Johnson’s ($JNJ) hot-selling Invokana has already come under scrutiny in the U.S. for safety issues, and now, it’s facing a new review across the pond. European regulators are sifting through data from a large ongoing clinical trial that showed an increase in toe amputations for patients taking the drug.

The European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has asked J&J’s Janssen unit for more information about whether Invokana (canagliflozin) triggered a spike in lower-limb amputations, and whether there should be changes to the way the med is used in the EU, Medscape reports.

Regulators based their probe on results from an ongoing clinical trial, called Canagliflozin Cardiovascular Assessment Study (CANVAS), which is slated to finish in 2017. The study is tracking about 4,000 Type 2 diabetes patients treated with either a 100 mg or 300 mg daily dose of Invokana or a placebo. The study so far has shown higher rates of lower-limb amputation in the Invokana groups.

The rate of lower-limb amputation in the study was 7 in 1,000 patient-years for the 100 mg dose and 5 in 1,000 patient-years for the 300 mg dose, compared with 3 in 1,000 patient-years with a placebo, the EMA said. Twelve completed clinical trials for Invokana did not show a higher rate of lower-limb amputations, although another ongoing study called CANVAS-R turned up a small increase in amputations, according to the Medscape article.

“Our commitment is to act in the best interests of patients,” Janssen CMO Dr. Amrit Ray said in a statement seen by FiercePharma. “We take all new information on safety seriously and respect and agree with the recommendation of the Independent Data Monitoring Committee to continue the CANVAS study."

J&J is not the only SGLT2 maker on thin ice with the EMA. The PRAC also plans to ask for data on other meds in the class, including AstraZeneca’s ($AZN) Farxiga and Eli Lilly ($LLY) and Boehringer Ingelheim’s Jardiance. “Based on this, the PRAC may decide to extend the scope of the review to cover these medicines,” the EMA said, as quoted by Medscape.

The EMA probe deals more bad news to J&J regarding Invokana’s safety. Last year, the FDA strengthened the warning on the drug’s label with information about bone mineral density and an increased risk of bone fractures. Regulators also revised the “Adverse Reactions” sections on Invokana and its metformin combo med Invokamet’s labels.

The safety setbacks do not bode well for Invokana as it competes in a crowded SGLT2 field. Jardiance and Farxiga do not have the same safety warnings in the U.S. And Lilly and Boehringer last year revealed that their Jardiance was the first diabetes drug to show it could lower the risk of heart attack, stroke and death from cardiovascular causes, potentially giving the drug a lift in a competitive market.

Still, some analysts think that J&J could benefit from Lilly and Boehringer’s new cardiac data with increased sales for Invokana. J&J CFO Dominic Caruso tends to agree. “We do think there’s a positive effect on the overall class as a result of the cardiovascular data that Lilly shared,” Caruso said last year on the company’s Q3 earnings call.

And if all goes to plan, Invokana will match Jardiance in cardiac safety. J&J plans to reveal its own data by 2017 that shows that its SGLT2 med can produce the same heart benefits at Jardiance, which would further dial up competition in the class.

- read the Medscape story (sub. req.)