FDA warning on J&J's Invokana adds more complexities to diabetes drug battles

Makers of a new class of diabetes drugs, SGLT2 inhibitors, seemed to catch a break last week when the FDA laid out a new safety warning for drugs in a competing class. But now one of the SGLT2 drugs, Johnson & Johnson's ($JNJ) hot-selling Invokana, is facing its own hurdle after the FDA said it was adding a warning for the risk for bone fractures and concerns about decreased bone density to its label.

In a drug safety communication on Thursday, the FDA pointed out that the label for Invokana, and Invokana and metformin combo Invokamet, already mentioned the risk of bone fractures. But the FDA said info from new studies confirmed they occur more often for people using the drug than for those taking a placebo. It said it also added the warning about loss of bone density after the agency "required" J&J to do a study over two years in 714 elderly patients and found that patients taking Invokana lost more bone density in their hips and lower spine than those who took a placebo lost.

Invokana was approved in 2013--and Invokamet a few months later--and the pair has been turning in big results for the drugmaker. Sales hit $318 million in the second quarter, more than double the $117 million in the same quarter a year ago. With $596 million in sales for first half of the year, the drug is on pace to hit blockbuster status this year.

But the whole realm of diabetes drugs--which includes SGLT2 inhibitors and other classes such as DPP-4 inhibitors--has been getting very competitive, so anything that improves or dampens a class, or a particular drug's standing in the market, is being evaluated closely by doctors and investors.

The boosted worry in taking Invokana comes even as rival SGLT2 inhibitor Jardiance from Eli Lilly ($LLY) and Boehringer Ingelheim last month was able to claim to be the first diabetes drug to show that it can lower the risk of heart attack, stroke and death from cardiovascular causes. Since diabetes can increase the risk of heart disease and strokes, having a drug that can treat the disease and a side effect of the disease would seem to be a big claim to be made.

Then the FDA late last month issued a new warning for the rival DPP-4 class of diabetes meds, saying they might cause "severe and disabling" joint pain. The agency said the symptoms sometimes cropped up immediately but other times surfaced years after a patient started taking one of the drugs. And if the drugs were stopped, the agency said, so did the joint pain.

The FDA added the joint-pain warning to the official labeling on the entire DPP-4 class, and that is a lot of drugs. The top seller is Merck's ($MRK) Januvia line, which includes single-agent pill Januvia (sitagliptin) and two Januvia-plus-metformin products sold under the Janumet brand. It also includes AstraZeneca's ($AZN) Onglyza (saxagliptin) and its metformin combo Kombiglyze; Takeda's Nesina (alogliptin), and two combo pills, Kazano and Oseni, as well as Eli Lilly ($LLY) and Boehringer Ingelheim's entry in the category, Tradjenta (linagliptin), and related combos Glyxambi and Jentadueto.

Peter Stein, who is VP of clinical research in diabetes and endocrinology for Merck, waved off big competition concerns over the added heart benefit of competing drug Jardiance last week. He told FiercePharma in an interview at the European Society of Cardiology Congress that people suffering from diabetes often need two or more agents to reach the blood sugar levels they need. Plus, Merck has its own SGLT2 drug, ertugliflozin, and a combo, in development. If "prescribers strongly begin to embrace SGLT2/DPP-4 fixed-dose combinations," well in the long run, Merck would benefit from that, Bernstein analyst Tim Anderson wrote in a recent note to clients.

- read the FDA announcement

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